Method for personalized therapy of celiac disease

Abstract

The present invention relates to a method for selecting or adjusting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one transglutaminase 2 (TG2) inhibitor to said subject, wherein selecting or adjusting the therapy regimen is based on human leukocyte antigen DQ haplotypes of said subject.

Description

[0001] 1 Method for personalized therapy of celiac disease Specification 5The present invention relates to a method for selecting or adjusting a therapyregimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least a treatment of celiac disease by administeringa therapeutically effective amount of at least one transglutaminase 2 (TG2) inhibitor to said subject, wherein selecting or adjusting the therapy regimen is10 based on human leukocyte antigen DQ haplotypes of said subject. Background of the invention Gluten-containing cereals are essential foods worldwide. However, in up to 2% of individuals, the ingestion of dietary gluten results in an abnormal immune 15 response in the small intestine and the development of celiac disease (CeD). Predisposing genotypes, human leukocyte antigen (HLA)-DQ2 and HLA-DQ8, are necessary but not sufficient for the manifestation of CeD. Diarrhea, weight loss, and malnutrition are classical bowel-related symptoms and signs of CeD, but anaemia, osteoporosis, and other autoimmune diseases, such as type 1 diabetes, 20 are also frequent manifestations. Currently, a gluten-free diet (GFD) is the only accepted treatment option for patients with CeD. However, the life-long strict and restrictive GFD is onerous and difficult to follow, and inadvertent gluten ingestion is common, resulting in ongoing 25 symptoms in nearly 50% of treated patients. Keeping the GFD also has a big impact on patients’ quality of life. Inadvertent gluten ingestion often leads to ongoing duodenal mucosal injury, with inflammation and morphological changes. Thus, even patients on GFD frequently have nutrient imbalances and deficiencies. 30 Previous study showed that despite having normal duodenal histomorphology, CeD patients on GFD differ from non-CeD controls on the molecular level and display insufficient expression of micronutrient transporter genes. The CeD autoantigen, transglutaminase 2 (TG2), is expressed in the intestine, 35 where it deamidates certain neutral glutamine residues to negatively charged glutamic acid residues in immunogenic gluten peptides. These modified gluten- peptides are more efficiently presented by HLA-DQ2 or HLA-DQ8 molecules on mucosal antigen-presenting cells, which leads to the activation and expansion of

[0002] DFP-P04535WO10 Application (final).docx 2 gluten-specific CD4+ type 1 helper T cells and the secretion of pro-inflammatory cytokines. Eventually, this process leads to villus atrophy, crypt hyperplasia, and the production of TG2 IgA. TG2, being crucial for CeD pathogenesis, is a pertinent target for therapy, and this approach was recently tested in a phase 2, 5 randomized, double-blind, placebo-controlled, dose-finding gluten challenge trial using the oral TG2 inhibitor Compound 1. In this phase 2 trial, Compound 1 attenuated gluten-induced duodenal mucosal injury, both morphological deterioration and inflammation, and improved symptoms and quality of life scores in patients with CeD. 10 However, some CeD patients were unexpectedly less responsive to the therapyregimen with Compound 1. Therefore there is a need for a method for selecting or adjusting a therapy regimen15 for a subject having been diagnosed with celiac disease based on subject’s background, in order to achieve optimal treatment response. It is the objective of the present invention to provide a method for selecting or adjusting a therapy regimen for a subject with celiac disease.20 The objective of the present invention is solved by the teaching of the independent claims. Further advantageous features, aspects and details of the invention are evident from the dependent claims, the description, the figures, and the examples of the present application. 25 Brief description of the invention Surprisingly, some CeD patients were less responsive to the therapy regimen with Compound 1, suggesting that they could benefit from a longer treatment or higher dosage. 30 The present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac 35 disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one transglutaminase 2 inhibitor to said subject, the method comprising:

[0003] DFP-P04535WO10 Application (final).docx 3 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise humanleukocyte antigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyte5 antigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- 10 specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten-specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to 15 (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject, wherein one or more therapeutic measures comprising a dose level of 20 transglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or more therapeutic measures comprising a dose level of transglutaminase 2 inhibitor, an 25 administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applys to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures30 based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes. Further preferred is a method, wherein the HLA-DQ2 haplotypes are selected from the35 group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA- DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes

[0004] DFP-P04535WO10 Application (final).docx 4 are selected from the group comprising or consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO. 5 Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subject10 in said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. As used herein, the wording “obtaining an ex-vivo sample of genetic material from 15 said subject” does not encompass surgical methods such as the taking of a biopsy. Preferred is a computer-implemented method for selecting a therapy regimen,wherein for a subject applying to the first gluten-sensitive DQ genotype group (i) 20 the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering a more potent TG2 inhibitor than a therapeuticregimen for a subject applying to the second gluten-sensitive DQ genotype group (ii) or third gluten-sensitive DQ genotype group (iii). 25 As used herein, the wording “more potent TG2 inhibitor” or “stronger TG2 inhibitor” means that this TG2 inhibitor leads to a better clinical outcome to the therapeutic regimen for a subject applying to the second gluten-sensitive DQ genotype group (ii) or third gluten-sensitive DQ genotype group (iii). 30 Preferred is a computer-implemented method for selecting a therapy regimen,wherein the human leukocyte antigen DQ haplotypes include at least HLA-DQ2and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / 35 HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising or consisting of: HLA-DQ8 homodimer,

[0005] DFP-P04535WO10 Application (final).docx 5 HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO. 5Preferred is a computer-implemented method for selecting a therapy regimen,wherein step (b) further comprises: identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or 10 identifying said subject as applying to second gluten-sensitive DQ genotype group (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 15 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05. Preferred is a computer-implemented method for selecting a therapy regimen,wherein a subject applying to the first gluten-sensitive DQ genotype group is20 characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0, preferably between -1.0 to -2.7 from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. Preferred is a computer-implemented method for selecting a therapy regimen,25 wherein a subject applying to the second gluten-sensitive DQ genotype group ischaracterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3, between -0.4 to -1.0 from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet.30 Preferred is a computer-implemented method for selecting a therapy regimen,wherein a subject applying to the third gluten-sensitive DQ genotype group ischaracterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7, preferably between -0.1 to -0.4 from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet.35 Preferred is a computer-implemented method for selecting a therapy regimen,wherein the first gluten-sensitive DQ genotype group has a more dysregulated genexpression than the third gluten-sensitive DQ genotype group, wherein more dysregulated genexpression is characterized by

[0006] DFP-P04535WO10 Application (final).docx 6 at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are at least 50% more downregulated in the first gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 50% – 90%; and / or5 at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are at least 30% more upregulated in the first gluten-sensitiveDQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 33% – 100%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM210 (inflammation) are at least 50% more upregulated in the first gluten-sensitive DQgenotype group than in the third gluten-sensitive DQ genotype group, preferablybetween 50% – 100%.Preferred is a computer-implemented method for selecting a therapy regimen,15 wherein the second gluten-sensitive DQ genotype group has a more dysregulated genexpression than the third gluten-sensitive DQ genotype group, wherein more dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are are between 10% – 49% more downregulated in the20 second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQgenotype group; and / or at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are between 10% – 29% more upregulated in the secondgluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype25 group, preferably between 12% – 25%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM2 (inflammation) are between 1% – 49% more upregulated in the second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 5% – 20%.30 Preferred is a computer-implemented method for selecting a therapy regimen,wherein the first gluten-sensitive DQ genotype group has a more dysregulatedgroup of (at least two) genes of a biological pathway than the third gluten-sensitiveDQ genotype group,35 wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by

[0007] DFP-P04535WO10 Application (final).docx 7 for transit amplifying cells, genes from the first gluten-sensitive DQ genotype group are on average at least 50% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or for mature enterocytes genes from the first gluten-sensitive DQ genotype group5 are on average at least 200% more downregulated than genes from the third gluten-sensitive DQ genotype group; and / or for immune cells, genes from the first gluten-sensitive DQ genotype group are onaverage at least 100% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or10 for duodenal transporter cells, genes from the first gluten-sensitive DQ genotypegroup are on average at least 200% more upregulated than genes from the thirdgluten-sensitive DQ genotype group. Preferred is a computer-implemented method for selecting a therapy regimen,15 wherein the second gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than the third gluten-sensitiveDQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by 20 for transit amplifying cells, genes from the second gluten-sensitive DQ genotype group are on average at least 20% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for mature enterocytes, genes from the second gluten-sensitive DQ genotypegroup are on average at least 50% more downregulated than genes from the third25 gluten-sensitive DQ genotype group; and / or for immune cells, genes from the second gluten-sensitive DQ genotype group areon average at least 5% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the second gluten-sensitive DQ30 genotype group are on average at least 50% more upregulated than genes from the third gluten-sensitive DQ genotype group. Preferred is a computer-implemented method for selecting a therapy regimen,wherein step b) further comprises 35 identifying said subject, at least based on the determined human leukocyte antigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or as a subject suffering from refractory coeliac disease; and applying said subject to the first gluten-sensitive DQ genotype group.

[0008] DFP-P04535WO10 Application (final).docx 8 Preferred is a computer-implemented method for selecting a therapy regimen,wherein the transglutaminase 2 inhibitor is a reversible transglutaminase 2 inhibitor or an irreversible transglutaminase 2 inhibitor. 5 Preferred is a computer-implemented method for selecting a therapy regimen,,wherein the transglutaminase 2 inhibitor is (S,E)-methyl-7-(1-(2-(2- ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H- imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1): 10 Preferred is a computer-implemented method for selecting a therapy regimen,wherein the therapy regimen comprises at least the use of a pharmaceutical composition comprising the TG2 inhibitor as an active ingredient, together with atleast one pharmaceutically acceptable carrier, excipient and / or diluent in the15 treatment of celiac disease of said subject, preferably wherein the pharmaceutical composition is a systemic formulation.Preferred is a computer-implemented method for selecting a therapy regimen,wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG220 inhibitor. Preferred is a method for for selecting a therapy regimen, wherein thetransglutaminase 2 inhibitor is administered to the subject as pharmaceutical composition comprising the TG2 inhibitor as an active ingredient, together with atleast one pharmaceutically acceptable carrier, excipient and / or diluent, preferably wherein the pharmaceutical composition is a systemic formulation, preferably an25 oral formulation. Description of the invention 30 Definitions Currently used predictive markers of therapy for celiac disease: a) Attenuation of gluten-induced small intestinal mucosal injury as measured bythe VH:CrD ratio. The VH:CrD is the morphometric measure of the length of 35 the small intestinal villi with respect to the depth of the crypts taken from an intestinal biopsy sample.

[0009] DFP-P04535WO10 Application (final).docx 9 (b) Attenuation of gluten-induced small intestinal mucosal inflammation asmeasured by the enumeration of intraepithelial lymphocytes (IELs) in histological sections. (c) Attenuation of gluten-induced serum antibodies such as anti-gliadin5 antibodies and autoantibodies against transglutaminase. The term “celiac disease” or “CD”, as used herein, refers to a disorder of theintestinal mucosa that is typically associated with villous atrophy, crypt hyperplasia, and / or inflammation of the mucosal lining of the small intestine. In 10 addition to the malabsorption of nutrients, individuals with celiac disease are at risk for mineral deficiency, vitamin deficiency, osteoporosis, autoimmune diseases, and intestinal malignancies, such as lymphoma and carcinoma. It is thought thatceliac disease is mostly caused by exposure to proteins such as gluten, e.g., glutenin and prolamine proteins which are present in wheat, rye, barley, oats, 15 millet, triticale, spelt, and kamut, in the appropriate genetic and environmental context. The term “refractory celiac disease” or “refractory CD”, as used herein, refers toa rare intestinal disorder characterized by persistent or recurrent symptoms and 20 signs of confirmed celiac disease despite a long-term, strict gluten-free diet, without other causes of villous atrophy or malignant complications, and with or without the presence of increased abnormal intraepitelial lymphocytes. Refractory celiac disease (RCD) is a complex autoimmune disorder much like the more common celiac disease but, unlike celiac disease, it is resistant or unresponsive to25 at least 6 – 12 months of treatment with a strict gluten-free diet. In celiac disease,treatment by means of a strict gluten-free diet is usually sufficient to overcome the disorder. However, refractory celiac disease is just that: refractory or stubbornly resistant to treatment. Only a small percentage (1-2%) of the people with celiac disease will develop RCD. 30 The term “sample” or “biological sample”, as used herein, includes a biologicalspecimen obtained from a subject. Suitable samples for use in the present invention include, without limitation, whole blood, plasma, serum, saliva, urine, stool (feces), tears, any other bodily fluid, tissue samples (e.g., biopsy), and35 cellular extracts thereof, e.g. red blood cellular extract. A preferred sample is a whole blood sample or a serum sample. The use of samples such as serum, saliva, and urine and isolation of nucleic acids from such samples + prior to HLA- DQ genotyping is well known in the art. As used herein, the wording “obtaining an

[0010] DFP-P04535WO10 Application (final).docx 10 ex-vivo sample of genetic material from said subject” does not encompass surgical methods such as the taking of a biopsy. Thus, suitable samples for use in the present invention include, without limitation, ex-vivo samples selected from whole blood, plasma, serum, saliva, urine, stool (feces), tears, any other bodily fluid, 5 tissue samples, and cellular extracts thereof, e.g. red blood cellular extract. A preferred ex-vivo sample is a whole blood sample or a serum sample. The term "subject", as used herein, refers to an individual or patient having been diagnosed with celiac disease, preferably having a risk of refractory celiac disease 10 or having been diagnosed with refractory celiac disease. The subject may be already in treatment of celiac disease or refractory celiac disease, e.g. may receive a therapeutically effective amount of at least one transglutaminase 2 inhibitor to said subject, preferably a therapeutically effective amount of Compound 1 or may receive a pharmaceutical composition comprising a15 therapeutically effective amount of Compound 1. A subject may be herein also an individual with well-controlled celiac disease who participated in the phase IIa,double-blind, randomised, placebo-controlled, dose-finding study on the efficacy and tolerability of a 6-week treatment with Compound 1 capsules vs. placebo insubjects undergoing gluten challenge. However, such a subject who participated20 in the phase IIa, double-blind, randomised, placebo-controlled, dose-finding study on the efficacy and tolerability of a 6-week treatment with Compound 1 capsulesvs. placebo in subjects undergoing gluten challenge herein may be preferably herein used as a comparative subject. 25 The term “human leukocyte antigen class II” or “HLA Class II”, as used herein, refers to a group of genes in the human leukocyte antigen (HLA) system, located within the Major Histocompatibility Complex (MHC) on chromosome 6. These genes encode for proteins that are expressed on the surface of antigen-presenting cells such as dendritic cells, B cells, and macrophages and crucial for the immune 30 system's ability to recognize and present antigens. The term "human leukocyte antigen (HLA) class II genotype", as used herein, refers to the specific combination of alleles (versions of a gene) at the HLA class II loci on chromosome 6 in an individual's genome. 35 The term “haplotype”, as used herein, refers to a group of genes that are located close to each other on the same chromosome within an organism and usually inherited together from a single parent. DFP-P04535WO10 Application (final).docx 11 The term "allele", as used herein, refers to one of two or more versions of a gene that are found at the same place, or locus, on a chromosome. 5 The term “dysregulated gene expression”, as used herein, refers to gluten- induced transcriptomic changes (dependent on the gene, higher or lower RNA level) measurable for patients suffering from celiac disease when challenged with gluten. Gluten-induced transcriptomic changes can preferably be determined by RNA-sequencing analysis of RNA extracts derived from patients suffering from 10 celiac disease. In contrary, gluten-induced transcriptomic changes are not observed in healthy subjects, e.g. subjects that are not suffering from celiac disease. Moreover, for patients suffering from celiac disease on gluten-free diet also no gluten-induced transcriptomic changes should be observable. Thus, the basic transcriptomic level would be e.g. a transcriptomic profile of either healthy 15 subject or patients not challenged with gluten. It has been surprisingly found that the human leukocyte antigen DQ haplotypes of a subject have an impact on the severity of gluten-induced transcriptomic changes for a subject. According to the invention, based on the human leukocyte antigen20 DQ haplotypes of a subject, a subject can be assigned to one of three gluten- sensitive DQ genotype groups. It has been found the gene expression, i.e. the gluten-induced transcriptomic changes is more dysregulated for subjects applyingto the first gluten-sensitive group than for subjects applying to the second or third gluten-sensitive group, and that the gene expression, i.e. the gluten-induced25 transcriptomic changes is more dysregulated for subjects applying to the secondgluten-sensitive group than for subjects applying to the third gluten-sensitive group. Thus, “more dysregulated gene expression” means that more gluten- induced transcriptomic changes (dependent on the gene, higher or lower RNA level) are observed when comparing DQ genotype group (i) (first gluten-sensitive 30 DQ genotype group) with DQ genotype group (ii) (second gluten-sensitive DQ genotype group), and / or when comparing DQ genotype group (ii) (second gluten- sensitive DQ genotype group) with DQ genotype group (iii) (third gluten-sensitive DQ genotype group). Moreover, “more dysregulated gene expression”preferably means that genes related to (encoding proteins for) mature enterocytes 35 and / or cell proliferation and / or inflammation are more up and / or downregulated for patients of DQ genotype group (i) (first gluten-sensitive DQ genotype group) than for patients of DQ genotype group (ii) and (iii) (second and third gluten-sensitive DQ genotype group). Furthermore, “more dysregulated gene expression” DFP-P04535WO10 Application (final).docx 12 preferably means that genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation are more up and / or downregulated for patients of DQ genotype group (ii) (second gluten-sensitive DQ genotype group)than for patients of DQ genotype group (iii) (second and third gluten-sensitive DQ 5 genotype group). Thus, preferably the first gluten-sensitive DQ genotype group has a more dysregulated genexpression than the third gluten-sensitive DQ genotype group, wherein more dysregulated genexpression is characterized by 10 at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are at least 50% more downregulated in the first gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 50% – 90%; and / orat least one, preferably more than one of the genes AGR2, MKI167, and CENPF15 (cell proliferation) are at least 30% more upregulated in the first gluten-sensitiveDQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 33% – 100%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM2 (inflammation) are at least 50% more upregulated in the first gluten-sensitive DQ20 genotype group than in the third gluten-sensitive DQ genotype group, preferablybetween 50% – 100%.Thus, preferably the second gluten-sensitive DQ genotype group has a more dysregulated genexpression than the third gluten-sensitive DQ genotype group,25 wherein more dysregulated genexpression is characterized byat least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are are between 10% – 49% more downregulated in thesecond gluten-sensitive DQ genotype group than in the third gluten-sensitive DQgenotype group; and / or30 at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are between 10% – 29% more upregulated in the secondgluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotypegroup, preferably between 12% – 25%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM235 (inflammation) are between 1% – 49% more upregulated in the second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 5% – 20%.DFP-P04535WO10 Application (final).docx 13 Moreover, preferably the first gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than the thirdgluten-sensitive DQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathway5 is characterized by for transit amplifying cells, genes from the first gluten-sensitive DQ genotype group are on average at least 50% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or for mature enterocytes genes from the first gluten-sensitive DQ genotype group10 are on average at least 200% more downregulated than genes from the third gluten-sensitive DQ genotype group; and / or for immune cells, genes from the first gluten-sensitive DQ genotype group are onaverage at least 100% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or15 for duodenal transporter cells, genes from the first gluten-sensitive DQ genotypegroup are on average at least 200% more upregulated than genes from the thirdgluten-sensitive DQ genotype group. Moreover, preferably the second gluten-sensitive DQ genotype group has a more20 dysregulated group of (at least two) genes of a biological pathway than the thirdgluten-sensitive DQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by for transit amplifying cells, genes from the second gluten-sensitive DQ genotype 25 group are on average at least 20% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for mature enterocytes, genes from the second gluten-sensitive DQ genotypegroup are on average at least 50% more downregulated than genes from the thirdgluten-sensitive DQ genotype group; and / or30 for immune cells, genes from the second gluten-sensitive DQ genotype group areon average at least 5% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the second gluten-sensitive DQgenotype group are on average at least 50% more upregulated than genes from35 the third gluten-sensitive DQ genotype group. The term “first gluten-sensitive DQ genotype group” or “high gluten-sensitivegroup”, as used herein, refers to the group of patients (i.e. subjects) who exhibit a DFP-P04535WO10 Application (final).docx 14 robust gluten-specific T-cell response when exposed to gluten. This immune reaction leads to a decrease in the villous height to crypt depth (VH:CrD) ratio and a marked epithelial response to interferon-gamma (IFNγ) during a six-week gluten challenge. Preferably, the patients (i.e. subjects) of the “first gluten-sensitive5 group” are characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0), particularly preferablybetween -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from GFD. The VH:CrD ratio of the first or high gluten-sensitive group is lower than the VH:CrD ratio of the second or mid gluten-sensitive group. 10 Thus, a subject applying to the “first gluten-sensitive DQ genotype group” ischaracterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0), preferably between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a 15 comparative subject on gluten-free diet. Moreover, a subject applying to the first gluten-sensitive DQ genotype group receiving a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of celiac disease is preferably also characterized by a 20 change in villous height to crypt depth (VH:CrD) ratio between -0.41 to -0.60 (-0.41 ≥ VH:CrD ratio > -0.60) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. As a reference value for the ratio villous height to crypt depth (VH:CrD) ratio of a 25 comparative subject on gluten-free diet a VH:CrD value of about 2.00, a VH:CrD value range between 2.00 – 2.20, or a VH:CrD value 2.11±0.34 may applied. Thecomparative subject on gluten-free diet may be also the subject in case the VH:CrD value of the subject on gluten-free diet is available. 30 The term “second gluten-sensitive DQ genotype group” or “mid gluten- sensitive group”, as used herein, describes patients (i.e. subjects) whodemonstrate a moderate gluten-specific T-cell response after being exposed to gluten. This immune response leads to alterations in the villous height to crypt depth (VH:CrD) ratio and an epithelial response to interferon-gamma (IFNγ) during 35 a six-week gluten challenge, with the severity of these changes falling between those observed in high and low gluten-sensitive individuals. Preferably, thepatients (i.e. subjects) of the “second gluten-sensitive group” are characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3 DFP-P04535WO10 Application (final).docx 15 (-0.1 ≥ VH:CrD ratio > -1.3), particularly preferably between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from GFD. The VH:CrD ratio of the second or mid gluten-sensitive group is lower than the VH:CrD ratio of the third or low gluten-sensitive group. 5 Thus, a subject applying to the second gluten-sensitive DQ genotype group ischaracterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3 (-0.1 ≥ VH:CrD ratio > -1.3), between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject 10 on gluten-free diet. Moreover, a subject applying to the second gluten-sensitive DQ genotype group receiving a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of celiac disease is preferably also characterized by a 15 change in villous height to crypt depth (VH:CrD) ratio between -0.16 to -0.40 (-0.16 ≥ VH:CrD ratio > -0.40) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. As a reference value for the ratio villous height to crypt depth (VH:CrD) ratio of a 20 comparative subject on gluten-free diet a VH:CrD value of about 2.00, a VH:CrD value range between 2.00 – 2.20, or a VH:CrD value 2.11±0.34 may applied. Thecomparative subject on gluten-free diet may be also the subject in case the VH:CrD value of the subject on gluten-free diet is available. 25 The term “third gluten-sensitive DQ genotype group” or “low gluten-sensitive group”, as used herein, refers to the group of patients (i.e. subjects) who exhibit a minimal gluten-specific T-cell response upon gluten exposure. Such immune reaction results in the maintenance of the villous height to crypt depth (VH:CrD) ratio and negligible epithelial response to interferon-gamma (IFNγ) throughout a30 six-week gluten challenge. Preferably, the patients (i.e. subjects) of the “thirdgluten-sensitive group” are characterized by a change in villous height to cryptdepth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7),particularly preferably between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from GFD.35 Thus, a subject applying to the third gluten-sensitive DQ genotype group ischaracterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7), preferably between -0.1 to -0.4 DFP-P04535WO10 Application (final).docx 16 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. Moreover, a subject applying to the third gluten-sensitive DQ genotype group 5 receiving a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of celiac disease is preferably also characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.15 (-0.05 ≥ VH:CrD ratio > -0.15) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 10 As a reference value for the ratio villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet a VH:CrD value of about 2.00, a VH:CrD value range between 2.00 – 2.20, or a VH:CrD value 2.11±0.34 may applied. Thecomparative subject on gluten-free diet may be also the subject in case the15 VH:CrD value of the subject on gluten-free diet is available. As used herein, a “pharmaceutically effective amount” of a transglutaminase 2 inhibitor is the amount or activity effective for achieving the desired physiological result, either in cells treated in vitro or in a patient treated in vivo. Specifically, a20 pharmaceutical effective amount is such an amount which is sufficient for inhibiting, for a certain period of time, one or more of the clinically defined pathological processes associated with transglutaminase 2. The effective amount can vary according to the specific compound of the formula (I) and additionally depends on a plurality of factors and conditions related to the subject to be treated 25 and the severity of the disease. If, for example, an inhibitor is to be administered in vivo, factors such as age, weight and health of the patients as well as dose reaction curves and data regarding toxicity obtained from preclinical animal studies are amongst the data to be considered. If the inhibitor in form of the compound of the formula (I) described herein is to be brought in contact with the cells in vivo, a30 plurality of preclinical in vitro studies would be designed in order to determineparameters such as absorption, half-life, dose, toxicity, etc.. Determining a pharmaceutically effective amount for a given pharmaceutically active ingredient is part of the ordinary skills of the one skilled in the art. 35 The term “more potent TG2 inhibitor” or “stronger TG2 inhibitor”, as used herein, refers to a TG2 inhibitor with a lower half maximal inhibitory concerntration (IC50) when compared to a different TG-2 inhibitor. For instance, treatment of patients of the DQ genotype group (i) (first gluten-sensitive DQ genotype group) DFP-P04535WO10 Application (final).docx 17 can be treated with TG2 inhibitor A (e.g. Compound 1) and patients of the DQ genotype group (ii) (second gluten-sensitive DQ genotype group) can be / are treated with TG2 inhibitor B (e.g. a different TG2 inhibitor than Compound 1 as disclosed herein), whereby TG2 inhibitor A (e.g. Compound 1) has lower IC50 than 5 TG2 inhibitor B (e.g. a different TG2 inhibitor than Compound 1 as disclosed herein). Method for selecting a therapeutic regimen The efficacy of the TG2 inhibitor Compound 1 to attenuate gluten-induced10 mucosal damage was previously reported in a proof-of-concept, randomized, double-blind, placebo-controlled, 6-week trial with a daily 3-g gluten challenge. TG2, the celiac autoantigen, has a pivotal role in gluten-induced pathogenesis,leading to small intestinal mucosal injury, with villus atrophy and crypt hyperplasia,the histological hallmarks of untreated CeD. Here, the inventors sought to assess15 the efficacy of Compound 1 in preventing gluten-induced mucosal damage at thetranscriptomic level (Example 1). Remarkably, a 100 mg daily dose of Compound1 inhibited virtually all the gluten-induced transcriptomic changes (Figure 1B, C).Active CeD is accompanied by compromised enterocyte maturation, crypthyperplasia due to the expansion of transit amplifying cells, immune cell infiltration,20 and decreased expression of duodenal transporters. GSZ scores based onpublished single-cell databases clearly indicated that TG2 inhibition efficiently blocked all the aforementioned gluten-induced intestinal manifestations in patients with CeD (Figure 2D). A recently published molecular histomorphometryregression model based on genome-wide transcriptomics analysis was validated25 in the independent study sample (Example 1). The inventors showed a significantaccordance between this new molecular tool and the traditional, more subjectivebiopsy-based microscopic histomorphometry reading. Overall, the transcriptomicfindings strongly support the results of the clinical trial with Compound 1, which demonstrated that the inhibition of TG2 activity can efficiently and specifically30 prevent gluten-induced mucosal damage. In addition, studies have shown that gluten-derived peptides may have innate immune stimulatory properties, outside the realm of adaptive immunity, which can lead to epithelial stress in CeD. The inventors’ data shows, however, that halting the adaptive immunity pathway inCeD pathogenesis is sufficient to prevent gluten-induced mucosal damage as the 35 inventors did not detect any molecular traces of mucosal damage remaining after the Compound 1 treatment.Gene ontology and reactome analyses indicated that gluten challenge most significantly affected genes related to the immune response, and especially to DFP-P04535WO10 Application (final).docx 18 interferon-mediated defense mechanisms (Figure 2B and 2C). This is inaccordance with previously published transcriptomic analyses of active CeD patients compared to patients on GFD or healthy controls. Notably, IFN-γsecreted by gluten-reactive T cells in the celiac intestine induces TG2 expression 5 and secretion, and thus favors the pathogenic auto-amplificatory loop of enhanced gluten deamidation by TG2, improved antigenic presentation on HLA-DQ2 or -DQ8, and subsequent gluten-specific T cell activation. The study as described in Example 1 confirms the prominent role of interferon signaling in CeDpathogenesis, in line with findings that nearly half of the gluten-induced gene10 expression changes in duodenal biopsies can be recapitulated in human intestinalepithelial organoids treated with IFN-γ (Figure 3A). The inventors also detectedthe suggested auto-amplificatory loop in the patient data, as TG2 expression positively correlated with the epithelial IFN-γ response (Figure 3F). Notably, TG2expression was induced by IFN-γ in human intestinal organoids ex vivo (Figure15 3E), suggesting mutual amplification between these two key players in CeD pathogenesis. The functional relevance of this amplification loop was indeed confirmed in the clinical study in which the inhibition of TG2 activity by Compound 1in patients with CeD significantly inhibited both the (epithelial) IFN-γ response(Figure 3B) and TG2 expression (Figure 3C), resulting in protection from villous20 atrophy and intraepithelial lymphocytosis (Figure 2D). However, even though TG2 inhibition exhibited significant efficacy, according to a comparison of the transcripts of the placebo / gluten challenge and the gluten challenge / Compound 1-treated group, which showed a transcriptome profile similar to the GFD groups, the inventors detected heterogeneity regarding the25 gluten-induced and IFN-γ-dependent cascade of pathogenic events among the Compound 1-treated and gluten-challenged CeD patients. Four of these patients still had a modestly active IFN-γ response, and the majority (three out of four)belonged to the HLA-DQ2.5 homozygous genotype (Figure 3C) (Example 2).HLA-DQ2.5 homozygous individuals have a fivefold higher risk of developing CeD30 compared to HLA-DQ2.5 heterozygous individuals, which has been linked to themore efficient presentation of deamidated gluten peptides to gluten-specific T cells. Moreover, homozygosity for HLA-DQ2 predisposes patients to developingmore rapid and severe villous atrophy and is associatedwith malignant complications such as refractory CeD type II (RCD II) and enteropathy-associated35 T-cell lymphoma (EATL). Along this line, the inventors also found that patientsbelonging to the high gluten-response DQ genotype group (G1) were more sensitive to gluten, as their VH:CrD dropped significantly more compared to patients belonging to the mid- and low-gluten response groups (G2 and G3) duringDFP-P04535WO10 Application (final).docx 19 the gluten challenge, both in the placebo and drug groups (Tables 4 and 6 andFigure 4A and 4B). Thus, even after drug treatment, VH:CrD decreasedsignificantly in the G1 versus G2 and G3 genotype groups after the gluten challenge. This was also evident when molecular histomorphometric features 5were assessed (Figure 9C and 9D). The inventors also have found that PPARsignaling and lipid metabolism, previously reported to be dysregulated in CeD, were less controlled in G1 group (Figure 9C and 9D). As IFN-γ is known to inhibitPPAR and lipid metabolism, it is conceivable that these are consequent of the overactive IFN-γ response in G1 group patients. Nevertheless, duodenal mucosal10 morphology and, especially, intraepithelial lymphocyte infiltration were significantly healthier in the Compound 1-treated group compared to the placebo group, indicating that patients with G1 phenotypes may benefit from a higher dose and / or prolonged treatment with Compound 1. The inventors suggest that theCompound 1 therapy program should include a personalized medicine approach 15 in which HLA-DQ stratification with TG2-inhibitor dose adjusted accordingly may lead to an optimal treatment response and a more thorough abrogation of the IFN- γ-induced mucosal damage. According to the transcriptomic analysis of humanintestinal organoids, Compound 1 does not appear to induce significanttranscriptomic changes in the organoid model (Figure 6), consistent with the20 clinical safety observed in the phase 2 challenge study. In conclusion, the strategy to inhibit TG2 activity as a key upstream effector in gluten-induced immune activation in CeD, which has been proven efficient in the clinical study, was mechanistically buttressed by the inventors’ transcriptomic analysis of the duodenal biopsies of patients treated or untreated with Compound25 1. Importantly, TG2 inhibition prominently prevented the gluten-induced IFN-γ response and further downstream pathways that led to mucosal inflammation, remodeling, and villous atrophy. The inventors analysis also suggested that based on the HLA-DQ 2.5 genetics, the dose or dose interval of Compound 1 should be adjusted for optimal efficacy. Moreover, CeD-associated gene30 expression changes were observable, even on a strict GFD indicating thatcomplete avoidance of gluten is impossible. In fact, a recent meta-analysis found that 15% of foods labeled as gluten-free and 28% labeled as naturally gluten-free contained more than 20 mg / kg of gluten, the cut-off for qualifying as gluten-free. Thus, an adjunctive TG2 inhibition-based therapy accompanied with the GFD 35 would especially benefit patients belonging to a highly gluten-sensitive group, possibly carrying a homozygous HLA-DQ genotype by providing protection against intestinal damage that can occur even in a low gluten environment. DFP-P04535WO10 Application (final).docx 20 Embodiments for Method for selecting a therapeutic regimenThe present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective 5 amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising:10 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to15 (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group,20 wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and25 (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of 30 said subject, with other words wherein the therapy regimen comprises one or more therapeutic measures comprising a dose level of transglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group35 (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, DFP-P04535WO10 Application (final).docx 21 wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, and preferably wherein the HLA-DQ2 haplotypes are selected from the group comprising or 5 consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising or10 consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO.15 Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, 20 wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. In all embodiment of the present invention, the therapy regimen preferably comprises TG2 inhibitor at a daily dose between 0.1 mg – 1000 mg, preferably25 between 0.5 mg – 500 mg, more preferably between 0.75 mg – 250 mg, mostpreferably between 1 mg – 100 mg. In some preferred embodiments, the therapyregimen preferably comprises TG2 inhibitor at a daily dose between 150 mg – 250mg, more preferably between 160 mg – 240 mg, more preferably between 170 mg– 230 mg, more preferably between 180 mg – 220 mg, more preferably between30 190 mg – 210 mg. In some preferred embodiments, the therapy regimenpreferably comprises TG2 inhibitor at a daily dose of (about) 200 mg.More preferably, in all embodiments of the present invention, therapy regimen forthe first gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily35 dose between 25 mg – 1000 mg, preferably between 25 mg – 500 mg, morepreferably between 25 mg – 250 mg, most preferably between 30 mg – 100 mg,and / or DFP-P04535WO10 Application (final).docx 22 wherein the therapy regimen for the second gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 5 mg – 750 mg, more preferablybetween 5 mg – 250 mg, preferably between 5 mg – 75 mg, most preferablybetween 10 mg – 30 mg, and / or5 wherein the therapy regimen for the third gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 0.1 mg – 500 mg, morepreferably between 0.1 mg – 250 mg, preferably between 0.1 mg – 50 mg, mostpreferably between 1 mg – 10 mg.10 In some preferred embodiments, the therapy regimen regimen for the first gluten- sensitive DQ genotype group preferably comprises TG2 inhibitor at a daily dose between 150 mg – 250 mg, more preferably between 160 mg – 240 mg, morepreferably between 170 mg – 230 mg, more preferably between 180 mg – 220 mg,more preferably between 190 mg – 210 mg. In some preferred embodiments, the15 therapy regimen preferably comprises TG2 inhibitor at a daily dose of (about) 200mg. In preferred embodiments of the present invention, the therapy regimen for the firstgluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose20 between 25 mg – 1000 mg, and / orwherein the therapy regimen for the second gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 5 mg – 750 mg, and / orwherein the therapy regimen for the third gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 0.1 mg – 500 mg.25 In further preferred embodiments of the present invention, the therapy regimen forthe first gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 25 mg – 500 mg, and / orwherein the therapy regimen for the second gluten-sensitive DQ genotype group30 comprises TG2 inhibitor at a daily dose between 5 mg – 250 mg, and / orwherein the therapy regimen for the third gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 0.1 mg – 250 mg.In even further preferred embodiments of the present invention, the therapy35 regimen for the first gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 25 mg – 250 mg, and / orwherein the therapy regimen for the second gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 5 mg – 75 mg, and / orDFP-P04535WO10 Application (final).docx 23 wherein the therapy regimen for the third gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 0.1 mg – 50 mg.In even further preferred embodiments of the present invention, the therapy5 regimen for the first gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 150 mg – 250 mg, more preferably between 160 mg – 240mg, more preferably between 170 mg – 230 mg, more preferably between 180 mg– 220 mg, more preferably between 190 mg – 210 mg, most preferably of (about)200 mg, and / or 10 wherein the therapy regimen for the second gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 5 mg – 75 mg, and / orwherein the therapy regimen for the third gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 0.1 mg – 50 mg.15 In some further preferred embodiments of the present invention, the therapy regimen for the first gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 30 mg – 100 mg, and / orwherein the therapy regimen for the second gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 10 mg – 30 mg, and / or20 wherein the therapy regimen for the third gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 1 mg – 10 mg.Preferably, the present invention relates to a computer-implemented method forselecting a therapy regimen for a subject having been diagnosed with celiac 25 disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to30 said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyte35 antigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,DFP-P04535WO10 Application (final).docx 24 wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, 5 wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , 10 wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor, 15 an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group(i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures20 based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, and preferably wherein the HLA-DQ2 haplotypes are selected from the group comprising or 25 consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising or30 consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein for a subject applying to the first gluten-sensitive DQ genotype group (i)35 the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering a more potent TG2 inhibitor than a therapeuticDFP-P04535WO10 Application (final).docx 25 regimen for a subject applying to the mid gluten-sensitive DQ genotype group (ii) or low gluten-sensitive DQ genotype group (iii). A more potent TG2 inhibitor refers to a TG2 inhibitor with a lower half maximal 5 inhibitory concerntration (IC50) when compared to a different TG-2 inhibitor. For instance, treatment of patients of the DQ genotype group (i) (first gluten-sensitive DQ genotype group) can be treated with Compound 1 and patients of the DQgenotype group (ii) or (iii) (second gluten-sensitive DQ genotype group) can be treated with a different TG2 inhibitor as disclosed herein, whereby Compound 110 has lower IC50 than the other TG2 inhibitor as disclosed herein. Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;15 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject.20 Preferably, the present invention relates to a computer-implemented method forselecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein 25 the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyte30 antigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or35 (iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- DFP-P04535WO10 Application (final).docx 26 specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and 5(c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of10 said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group 15 (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA-20 DQ9 haplotypes, at least HLA-DQ2 and HLA-DQ8 haplotypes, an preferablywherein the HLA-DQ2 haplotypes are selected from the group consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and25 wherein the HLA-DQ8 haplotypes are selected from the group consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO.30 Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, 35 wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. DFP-P04535WO10 Application (final).docx 27 Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the 5 treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,10 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,15 (ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- 20 specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQ25 genotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or more30 therapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said 35 subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein for a subject applying to the first gluten-sensitive DQ genotype group (i)the therapeutic regimen comprises one or more of administering the TG2 inhibitor DFP-P04535WO10 Application (final).docx 28 at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering a more potent TG2 inhibitor than a therapeutic regimen for a subject applying to the second gluten-sensitive DQ genotype group(ii) or third gluten-sensitive DQ genotype group (iii),5 wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, at least HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA- DQ2 haplotypes are selected from the group consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; 10 HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one 15 copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO. Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;20 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 25 Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein 30 the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyte35 antigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,DFP-P04535WO10 Application (final).docx 29 (ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, 5 wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and10 (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of15 said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group 20 (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA-25 DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; 30 HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising of consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one35 copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO; wherein step (b) further comprises: DFP-P04535WO10 Application (final).docx 30 identifying said subject as applying to first gluten-sensitive DQ genotype group (i) ifthe HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group 5 (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii)if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy10 of DQA1*05. Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;15 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 20 Preferably, the therapy regimen preferably comprises TG2 inhibitor at a daily dose between 0.1 mg – 1000 mg, preferably between 0.5 mg – 500 mg, more preferablybetween 0.75 mg – 250 mg, most preferably between 1 mg – 100 mg. In somepreferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at adaily dose between 150 mg – 250 mg, more preferably between 160 mg – 24025 mg, more preferably between 170 mg – 230 mg, more preferably between 180 mg– 220 mg, more preferably between 190 mg – 210 mg. In some preferredembodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose of (about) 200 mg.30 More preferably, the therapy regimen for the first gluten-sensitive DQ genotypegroup comprises TG2 inhibitor at a daily dose between 25 mg – 1000 mg,preferably between 25 mg – 500 mg, more preferably between 25 mg – 250 mg,most preferably between 30 mg – 100 mg, and / orwherein the therapy regimen for the second gluten-sensitive DQ genotype group35 comprises TG2 inhibitor at a daily dose between 5 mg – 750 mg, more preferablybetween 5 mg – 250 mg, preferably between 5 mg – 75 mg, most preferablybetween 10 mg – 30 mg, and / orDFP-P04535WO10 Application (final).docx 31 wherein the therapy regimen for the third gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 0.1 mg – 500 mg, morepreferably between 0.1 mg – 250 mg, preferably between 0.1 mg – 50 mg, mostpreferably between 1 mg – 10 mg.5 In some preferred embodiments, the therapy regimen regimen for the first gluten- sensitive DQ genotype group preferably comprises TG2 inhibitor at a daily dose between 150 mg – 250 mg, more preferably between 160 mg – 240 mg, morepreferably between 170 mg – 230 mg, more preferably between 180 mg – 220 mg,10 more preferably between 190 mg – 210 mg. In some preferred embodiments, thetherapy regimen preferably comprises TG2 inhibitor at a daily dose of (about) 200 mg. Preferably, the present invention relates to a computer-implemented method for 15 selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by 20 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject;25 (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,30 wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more 35 dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , DFP-P04535WO10 Application (final).docx 32 wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or more5 therapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said 10 subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein for a subject applying to the first gluten-sensitive DQ genotype group (i) the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer 15 duration of treatment, administering a stronger TG2 inhibitor than a therapeutic regimen for a subject applying to the mid gluten-sensitive DQ genotype group (ii) or low gluten-sensitive DQ genotype group (iii), wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- 20 DQ9 haplotypes, at least HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and25 wherein the HLA-DQ8 haplotypes are selected from the group consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO; wherein step (b) further comprises:30 identifying said subject as applying to first gluten-sensitive DQ genotype group (i) ifthe HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, 35 DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii)if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 DFP-P04535WO10 Application (final).docx 33 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05. Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac 5 disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to10 said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyte15 antigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- 20 specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature25 enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, 30 of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic 35 measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, DFP-P04535WO10 Application (final).docx 34 wherein for a subject applying to the first gluten-sensitive DQ genotype group (i) the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering a more potent TG2 inhibitor than a therapeutic 5regimen for a subject applying to the second gluten-sensitive DQ genotype group(ii) or third gluten-sensitive DQ genotype group (iii),wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, 10 wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and 15 wherein the HLA-DQ8 haplotypes are selected from the group comprising or consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein step (b) further comprises: 20 identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group(ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, 25 DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii)if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05.30 Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, 35 wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. DFP-P04535WO10 Application (final).docx 35 Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the 5 treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,10 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,15 (ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- 20 specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQ25 genotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or more 30 therapeutic measures selected from a dose level of transglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said 35 subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, DFP-P04535WO10 Application (final).docx 36 wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or 5 consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising or 10 consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG2 inhibitor. 15 In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-yl- amino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1). 20 Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subject25 in said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. Preferably, the present invention relates to a computer-implemented method for 30 selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by 35 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,DFP-P04535WO10 Application (final).docx 37 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to 5(i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group,10 wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and15 (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of20 said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group 25 (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA-30 DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; 35 HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising or consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DFP-P04535WO10 Application (final).docx 38 DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein step (b) further comprises: identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, 5 DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group(ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii)10 if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05, wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG2 inhibitor. 15 In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1).20 Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, 25 wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. Preferably, the present invention relates to a method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the 30 therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising:35 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; DFP-P04535WO10 Application (final).docx 39 (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or5 (iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, 10 wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , 15 wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or more therapeutic measures selected from a dose level of transglutaminase 2 inhibitor, 20 an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures25 based on the DQ genotype group of said subject, wherein for a subject applying to the first gluten-sensitive DQ genotype group (i) the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering amore potent TG2 inhibitor than a therapeutic 30 regimen for a subject applying to the second gluten-sensitive DQ genotype group (ii) or third gluten-sensitive DQ genotype group (iii), wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the 35 HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and DFP-P04535WO10 Application (final).docx 40 wherein the HLA-DQ8 haplotypes are selected from the group comprising or consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one 5 copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO; wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG2 inhibitor. In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)-10 methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1). Preferred is a computer-implemented method for selecting a therapy regimen,15 wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of20 human leukocyte antigen DQ alleles and haplotypes of said subject. Preferably, the present invention relates to a method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of 25 at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,30 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,35 (ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, DFP-P04535WO10 Application (final).docx 41 wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature 5 enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, 10 of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic 15 measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein for a subject applying to the first gluten-sensitive DQ genotype group (i)20 the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering amore potent TG2 inhibitor than a therapeuticregimen for a subject applying to the second gluten-sensitive DQ genotype group (ii) or third gluten-sensitive DQ genotype group (iii),25 wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; 30 HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising or consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, 35 DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO; wherein step (b) further comprises: DFP-P04535WO10 Application (final).docx 42 identifying said subject as applying to first gluten-sensitive DQ genotype group (i) ifthe HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group 5 (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii)if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy10 of DQA1*05, wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG2 inhibitor. In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3- 15 ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1). Preferred is a computer-implemented method for selecting a therapy regimen,wherein before step (a) the method further comprises steps (a’) and (a’’):20 (a’) obtaining an ex-vivo sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 25 Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the 30 treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,35 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to DFP-P04535WO10 Application (final).docx 43 (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- 5 specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature10 enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, 15 of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic 20 measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-25 DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; 30 HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one35 copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0) from a DFP-P04535WO10 Application (final).docx 44 villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3 (-0.1 ≥ VH:CrD ratio > -1.3) from a villous 5 height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet; 10 preferably wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or 15 wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth 20 (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’):25 (a’) obtaining a sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 30 Thus, in embodiments wherein wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or 35 wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3 (-0.1 ≥ VH:CrD ratio > -1.3) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or DFP-P04535WO10 Application (final).docx 45 wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet; preferably wherein a subject applying to (i) is characterized by a change of villous 5 height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous10 height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet,15 step b) preferably comprises:(b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or20 (iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0, preferably between -1.0 to -2.7 from a villous height to crypt depth25 (VH:CrD) ratio of a comparative subject on gluten-free diet; wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3, between -0.4 to -1.0 from a villous height to crypt depth (VH:CrD) ratio30 of a comparative subject on gluten-free diet; wherein third gluten-sensitive DQ genotype group has a gluten-specific T cell response characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7, preferably between -0.1 to -0.4 from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, 35 wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation. DFP-P04535WO10 Application (final).docx 46 Moreover, a subject applying to the first gluten-sensitive DQ genotype group receiving a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of celiac disease is preferably also characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.41 to -0.60 5 (-0.41 ≥ VH:CrD ratio > -0.60) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. Moreover, a subject applying to the second gluten-sensitive DQ genotype group receiving a therapeutically effective amount of at least one transglutaminase 2 10 inhibitor in the treatment of celiac disease is preferably also characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.16 to -0.40 (-0.16 ≥ VH:CrD ratio > -0.40) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 15 Moreover, a subject applying to the third gluten-sensitive DQ genotype group receiving a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of celiac disease is preferably also characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.15 (-0.05 ≥ VH:CrD ratio > -0.15) from a villous height to crypt depth (VH:CrD) ratio of20 a comparative subject on gluten-free diet. Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a 25 therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising:30 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to35 (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,DFP-P04535WO10 Application (final).docx 47 wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, 5 wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , 10 wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or more therapeutic measures selected from a dose level of transglutaminase 2 inhibitor, 15 an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures20 based on the DQ genotype group of said subject, wherein a subject applying to (i) receiving a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of celiac disease is characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.41 to -0.60 (-0.41 ≥ VH:CrD ratio > -0.60) from a villous height to crypt depth25 (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) receiving a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of celiac disease is characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.16 to -0.40 (-0.16 ≥ VH:CrD ratio > -0.40) from a villous height to crypt depth30 (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) receiving a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of celiac disease is characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.15 (-0.05 ≥ VH:CrD ratio > -0.15) from a villous height to crypt depth35 (VH:CrD) ratio of a comparative subject on gluten-free diet. Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac DFP-P04535WO10 Application (final).docx 48 disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by 5 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject;10 (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,15 wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more 20 dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, 25 administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 30 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject,35 wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, DFP-P04535WO10 Application (final).docx 49 wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; 5 HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, 10 wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth 15 (VH:CrD) ratio between -0.1 to -1.3 (-0.1 ≥ VH:CrD ratio > -1.3) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7) from a villous20 height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining a sample of genetic material from said subject;25 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 30 Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein 35 the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a’) obtaining an ex-vivo sample of genetic material from said subject;DFP-P04535WO10 Application (final).docx 50 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject, 5(a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to10 (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group,15 wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and20 (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of25 said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group 30 (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA-35 DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: DFP-P04535WO10 Application (final).docx 51 HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising 5 HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0) from a 10 villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3 (-0.1 ≥ VH:CrD ratio > -1.3) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet,15 and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet; preferably 20 wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth 25 (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous30 height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG2 inhibitor. In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)-35 methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1). DFP-P04535WO10 Application (final).docx 52 Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining a sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subject5 in said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. Preferably, the present invention relates to a computer-implemented method for 10 selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by 15 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject;20 (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,25 wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more 30 dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, 35 administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor,DFP-P04535WO10 Application (final).docx 53 an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said 5 subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, 10 wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and 15 wherein the HLA-DQ8 haplotypes are selected from the group comprising HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein step (b) further comprises: 20 identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, 25 DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05, 30 wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth 35 (VH:CrD) ratio between -0.1 to -1.3 (-0.1 ≥ VH:CrD ratio > -1.3) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or DFP-P04535WO10 Application (final).docx 54 wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, preferably 5 wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth 10 (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous15 height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining a sample of genetic material from said subject;20 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 25 Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein 30 the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyte35 antigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,DFP-P04535WO10 Application (final).docx 55 (ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, 5 wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, 10 administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimenselected from one or more therapeutic measures comprising a dose level oftransglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein 15 one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein for a subject applying to the first gluten-sensitive DQ genotype group (i) 20 the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering a more potent TG2 inhibitor than a therapeutic regimen for a subject applying to the second gluten-sensitive DQ genotype group (ii) or third gluten-sensitive DQ genotype group (iii),25 wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA-DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, 30 wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and 35 wherein the HLA-DQ8 haplotypes are selected from the group comprising HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, DFP-P04535WO10 Application (final).docx 56 wherein step (b) further comprises: identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or 5 identifying said subject as applying to second gluten-sensitive DQ genotype group (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 10 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05, wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free15 diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3 (-0.1 ≥ VH:CrD ratio > -1.3) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or 20 wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet; preferably wherein a subject applying to (i) is characterized by a change of villous height to 25 crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous 30 height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 35 Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining a sample of genetic material from said subject;DFP-P04535WO10 Application (final).docx 57 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 5 Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the 10 treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a’) obtaining an ex-vivo sample of genetic material from said subject;15 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject, (a) providing a human leukocyte antigen class II genotype of said subject,20 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,25 (ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten-30 specific T cell response than the third gluten-sensitive DQ genotype group; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, 35 of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase DFP-P04535WO10 Application (final).docx 58 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures 5 based on the DQ genotype group of said subject, wherein for a subject applying to the first gluten-sensitive DQ genotype group (i) the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering a more potent TG2 inhibitor than a therapeutic 10 regimen for a subject applying to the second gluten-sensitive DQ genotype group (ii) or third gluten-sensitive DQ genotype group (iii), wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the 15 HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising 20 HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein step (b) further comprises: identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if 25 the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, DQ8 / DQ2, DQ2.5 / DQ2.2, or 30 identifying said subject as applying to third gluten-sensitive DQ genotype group (iii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05, wherein a subject applying to (i) is characterized by a change of villous height to 35 crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or DFP-P04535WO10 Application (final).docx 59 wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3 (-0.1 ≥ VH:CrD ratio > -1.3) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or 5 wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet; preferably wherein a subject applying to (i) is characterized by a change of villous height to 10 crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous 15 height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, 20 wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG2 inhibitor. In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3- 25 ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1). Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’):30 (a’) obtaining a sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 35 Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a DFP-P04535WO10 Application (final).docx 60 therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to 5 said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyte10 antigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- 15 specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature20 enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, 25 of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic 30 measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-35 DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: DFP-P04535WO10 Application (final).docx 61 HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising 5 HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein the first gluten-sensitive DQ genotype group has a more dysregulated genexpression than the third gluten-sensitive DQ genotype group,10 wherein more dysregulated genexpression is characterized byat least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are at least 50% more downregulated in the first gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 50% – 90%; and / or15 at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are at least 30% more upregulated in the first gluten-sensitiveDQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 33% – 100%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM220 (inflammation) are at least 50% more upregulated in the first gluten-sensitive DQgenotype group than in the third gluten-sensitive DQ genotype group, preferablybetween 50% – 100%; andwherein the second gluten-sensitive DQ genotype group has a more dysregulatedgenexpression than the third gluten-sensitive DQ genotype group,25 wherein more dysregulated genexpression is characterized byat least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are between 10% – 49% more downregulated in thesecond gluten-sensitive DQ genotype group than in the third gluten-sensitive DQgenotype group; and / or30 at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are between 10% – 29% more upregulated in the secondgluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotypegroup, preferably between 12% – 25%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM235 (inflammation) are between 1% – 49% more upregulated in the second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 5% – 20%.DFP-P04535WO10 Application (final).docx 62 Preferably, the therapy regimen preferably comprises TG2 inhibitor at a daily dose between 0.1 mg – 1000 mg, preferably between 0.5 mg – 500 mg, more preferablybetween 0.75 mg – 250 mg, most preferably between 1 mg – 100 mg. In somepreferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at 5a daily dose between 150 mg – 250 mg, more preferably between 160 mg – 240mg, more preferably between 170 mg – 230 mg, more preferably between 180 mg– 220 mg, more preferably between 190 mg – 210 mg. In some preferredembodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose of (about) 200 mg. 10 More preferably, the therapy regimen for the first gluten-sensitive DQ genotypegroup comprises TG2 inhibitor at a daily dose between 25 mg – 1000 mg,preferably between 25 mg – 500 mg, more preferably between 25 mg – 250 mg,most preferably between 30 mg – 100 mg, and / or15 wherein the therapy regimen for the second gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 5 mg – 750 mg, more preferablybetween 5 mg – 250 mg, preferably between 5 mg – 75 mg, most preferablybetween 10 mg – 30 mg, and / orwherein the therapy regimen for the third gluten-sensitive DQ genotype group20 comprises TG2 inhibitor at a daily dose between 0.1 mg – 500 mg, morepreferably between 0.1 mg – 250 mg, preferably between 0.1 mg – 50 mg, mostpreferably between 1 mg – 10 mg.In some preferred embodiments, the therapy regimen regimen for the first gluten- 25 sensitive DQ genotype group preferably comprises TG2 inhibitor at a daily dose between 150 mg – 250 mg, more preferably between 160 mg – 240 mg, morepreferably between 170 mg – 230 mg, more preferably between 180 mg – 220 mg,more preferably between 190 mg – 210 mg. In some preferred embodiments, thetherapy regimen preferably comprises TG2 inhibitor at a daily dose of (about) 20030 mg. Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining a sample of genetic material from said subject;35 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. DFP-P04535WO10 Application (final).docx 63 Preferably, wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0 (-0.7 ≥ VH:CrD ratio ≥ -3.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject 5 on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -1.3 (-0.1 ≥ VH:CrD ratio > -1.3) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or 10 wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.05 to -0.7 (-0.05 ≥ VH:CrD ratio > -0.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet; preferably wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio 15 ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villousheight to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet,20 and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 25 Preferred is a method, wherein the first gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than thethird gluten-sensitive DQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by 30 for transit amplifying cells, genes from the first gluten-sensitive DQ genotype group are on average at least 50% more upregulated than genes fromthe third gluten-sensitive DQ genotype group, and / or for mature enterocytes genes from the first gluten-sensitive DQ genotypegroup are on average at least 200% more downregulated than genes from the35 third gluten-sensitive DQ genotype group; and / or for immune cells, genes from the first gluten-sensitive DQ genotype groupare on average at least 100% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or DFP-P04535WO10 Application (final).docx 64 for duodenal transporter cells, genes from the first gluten-sensitive DQgenotype group are on average at least 200% more upregulated than genes fromthe third gluten-sensitive DQ genotype group; wherein the second gluten-sensitive DQ genotype group has a more dysregulated 5group of (at least two) genes of a biological pathway than the third gluten-sensitiveDQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by for transit amplifying cells, genes from the second gluten-sensitive DQ 10 genotype group are on average at least 20% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for mature enterocytes, genes from the second gluten-sensitive DQgenotype group are on average at least 50% more downregulated than genesfrom the third gluten-sensitive DQ genotype group; and / or15 for immune cells, genes from the second gluten-sensitive DQ genotypegroup are on average at least 5% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the second gluten-sensitive DQgenotype group are on average at least 50% more upregulated than genes from20 the third gluten-sensitive DQ genotype group. Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a 25 therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising:30 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to35 (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,DFP-P04535WO10 Application (final).docx 65 wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, 5 wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , 10 wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor, 15 an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures20 based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: 25 HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, 30 DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein the first gluten-sensitive DQ genotype group has a more dysregulated genexpression than the third gluten-sensitive DQ genotype group, wherein 35 more dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are at least 50% more downregulated in the first gluten-DFP-P04535WO10 Application (final).docx 66 sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 50% – 90%; and / orat least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are at least 30% more upregulated in the first gluten-sensitive5 DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 33% – 100%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM2 (inflammation) are at least 50% more upregulated in the first gluten-sensitive DQgenotype group than in the third gluten-sensitive DQ genotype group, preferably10 between 50% – 100%; andwherein the second gluten-sensitive DQ genotype group has a more dysregulatedgenexpression than the third gluten-sensitive DQ genotype group, wherein stronger dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF415 (mature enterocytes) are are between 10% – 49% more downregulated in thesecond gluten-sensitive DQ genotype group than in the third gluten-sensitive DQgenotype group; and / or at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are between 10% – 29% more upregulated in the second20 gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotypegroup, preferably between 12% – 25%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM2 (inflammation) are between 1% – 49% more upregulated in the second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,25 preferably between 5% – 20%.wherein the TG2 inhibitor is a reversible TG2inhibitor or an irreversible TG2 inhibitor. Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’):30 (a’) obtaining a sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 35 Preferably, wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 DFP-P04535WO10 Application (final).docx 67 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous 5 height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 10 Preferred is a method, wherein the first gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than thethird gluten-sensitive DQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathway15 is characterized by for transit amplifying cells, genes from the first gluten-sensitive DQ genotype group are on average at least 50% more upregulated than genes fromthe third gluten-sensitive DQ genotype group, and / or for mature enterocytes genes from the first gluten-sensitive DQ genotype20 group are on average at least 200% more downregulated than genes from the third gluten-sensitive DQ genotype group; and / or for immune cells, genes from the first gluten-sensitive DQ genotype groupare on average at least 100% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or25 for duodenal transporter cells, genes from the first gluten-sensitive DQgenotype group are on average at least 200% more upregulated than genes fromthe third gluten-sensitive DQ genotype group; wherein the second gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than the third gluten-sensitive30 DQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by for transit amplifying cells, genes from the second gluten-sensitive DQ genotype group are on average at least 20% more upregulated than genes from35 the third gluten-sensitive DQ genotype group, and / or for mature enterocytes, genes from the second gluten-sensitive DQgenotype group are on average at least 50% more downregulated than genesfrom the third gluten-sensitive DQ genotype group; and / or DFP-P04535WO10 Application (final).docx 68 for immune cells, genes from the second gluten-sensitive DQ genotypegroup are on average at least 5% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the second gluten-sensitive DQ5 genotype group are on average at least 50% more upregulated than genes from the third gluten-sensitive DQ genotype group. In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3- 10 ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1). Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac 15 disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to20 said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyte25 antigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- 30 specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature35 enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , DFP-P04535WO10 Application (final).docx 69 wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or more5 therapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said 10 subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the 15 HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising 20 HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein step (b) further comprises: identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if 25 the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, DQ8 / DQ2, DQ2.5 / DQ2.2, or 30 identifying said subject as applying to third gluten-sensitive DQ genotype group (iii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05, wherein the first gluten-sensitive DQ genotype group has a stronger dysregulated35 genexpression than the third gluten-sensitive DQ genotype group, wherein stronger dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are at least 50% more downregulated in the first gluten-DFP-P04535WO10 Application (final).docx 70 sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 50% – 90%; and / orat least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are at least 30% more upregulated in the first gluten-sensitive5 DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 33% – 100%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM2 (inflammation) are at least 50% more upregulated in the first gluten-sensitive DQgenotype group than in the third gluten-sensitive DQ genotype group, preferably10 between 50% – 100%; andwherein the second gluten-sensitive DQ genotype group has a stronger dysregulated genexpression than the third gluten-sensitive DQ genotype group, wherein stronger dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF415 (mature enterocytes) are are between 10% – 49% more downregulated in thesecond gluten-sensitive DQ genotype group than in the third gluten-sensitive DQgenotype group; and / or at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are between 10% – 29% more upregulated in the second20 gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotypegroup, preferably between 12% – 25%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM2 (inflammation) are between 1% – 49% more upregulated in the second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,25 preferably between 5% – 20%.Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining a sample of genetic material from said subject;30 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 35 Preferably, wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or DFP-P04535WO10 Application (final).docx 71 wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or 5 wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. Preferred is a method, wherein the first gluten-sensitive DQ genotype group has a10 more dysregulated group of (at least two) genes of a biological pathway than thethird gluten-sensitive DQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by for transit amplifying cells, genes from the first gluten-sensitive DQ15 genotype group are on average at least 50% more upregulated than genes fromthe third gluten-sensitive DQ genotype group, and / or for mature enterocytes genes from the first gluten-sensitive DQ genotypegroup are on average at least 200% more downregulated than genes from the third gluten-sensitive DQ genotype group; and / or20 for immune cells, genes from the first gluten-sensitive DQ genotype groupare on average at least 100% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the first gluten-sensitive DQgenotype group are on average at least 200% more upregulated than genes from25 the third gluten-sensitive DQ genotype group; wherein the second gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than the third gluten-sensitiveDQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathway30 is characterized by for transit amplifying cells, genes from the second gluten-sensitive DQ genotype group are on average at least 20% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for mature enterocytes, genes from the second gluten-sensitive DQ35 genotype group are on average at least 50% more downregulated than genesfrom the third gluten-sensitive DQ genotype group; and / or DFP-P04535WO10 Application (final).docx 72 for immune cells, genes from the second gluten-sensitive DQ genotypegroup are on average at least 5% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the second gluten-sensitive DQ5 genotype group are on average at least 50% more upregulated than genes from the third gluten-sensitive DQ genotype group. In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3- 10 ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1). Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac 15 disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to20 said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyte25 antigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- 30 specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature35 enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , DFP-P04535WO10 Application (final).docx 73 wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or more5 therapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said 10 subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein for a subject applying to the first gluten-sensitive DQ genotype group (i) the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer 15 duration of treatment, administering a more potent TG2 inhibitor than a therapeutic regimen for a subject applying to the second gluten-sensitive DQ genotype group (ii) or third gluten-sensitive DQ genotype group (iii), wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- 20 DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and 25 wherein the HLA-DQ8 haplotypes are selected from the group comprising HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein step (b) further comprises: 30 identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, 35 DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 DFP-P04535WO10 Application (final).docx 74 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05, wherein the first gluten-sensitive DQ genotype group has a stronger dysregulated genexpression than the third gluten-sensitive DQ genotype group, 5 wherein stronger dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are at least 50% more downregulated in the first gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 50% – 90%; and / or10 at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are at least 30% more upregulated in the first gluten-sensitiveDQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 33% – 100%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM215 (inflammation) are at least 50% more upregulated in the first gluten-sensitive DQgenotype group than in the third gluten-sensitive DQ genotype group, preferablybetween 50% – 100%; andwherein the second gluten-sensitive DQ genotype group has a stronger dysregulated genexpression than the third gluten-sensitive DQ genotype group,20 wherein stronger dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are are between 10% – 49% more downregulated in thesecond gluten-sensitive DQ genotype group than in the third gluten-sensitive DQgenotype group; and / or25 at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are between 10% – 29% more upregulated in the secondgluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotypegroup, preferably between 12% – 25%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM230 (inflammation) are between 1% – 49% more upregulated in the second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 5% – 20%.Preferred is a method, wherein before step (a) the method further comprises steps35 (a’) and (a’’): (a’) obtaining a sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, DFP-P04535WO10 Application (final).docx 75 wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. Preferably, wherein a subject applying to (i) is characterized by a change of villous 5 height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous 10 height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 15 Preferred is a method, wherein the first gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than thethird gluten-sensitive DQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by 20 for transit amplifying cells, genes from the first gluten-sensitive DQ genotype group are on average at least 50% more upregulated than genes fromthe third gluten-sensitive DQ genotype group, and / or for mature enterocytes genes from the first gluten-sensitive DQ genotypegroup are on average at least 200% more downregulated than genes from the25 third gluten-sensitive DQ genotype group; and / or for immune cells, genes from the first gluten-sensitive DQ genotype groupare on average at least 100% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the first gluten-sensitive DQ30 genotype group are on average at least 200% more upregulated than genes fromthe third gluten-sensitive DQ genotype group; wherein the second gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than the third gluten-sensitiveDQ genotype group,35 wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by DFP-P04535WO10 Application (final).docx 76 for transit amplifying cells, genes from the second gluten-sensitive DQ genotype group are on average at least 20% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for mature enterocytes, genes from the second gluten-sensitive DQ5 genotype group are on average at least 50% more downregulated than genesfrom the third gluten-sensitive DQ genotype group; and / or for immune cells, genes from the second gluten-sensitive DQ genotypegroup are on average at least 5% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or10 for duodenal transporter cells, genes from the second gluten-sensitive DQgenotype group are on average at least 50% more upregulated than genes from the third gluten-sensitive DQ genotype group. Preferably, the present invention relates to a computer-implemented method for 15 selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by 20 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject;25 (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,30 wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more 35 dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , DFP-P04535WO10 Application (final).docx 77 wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or more5 therapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said 10 subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, 15 wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and 20 wherein the HLA-DQ8 haplotypes are selected from the group comprising HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein step (b) further comprises: 25 identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or identifying said subject as applying to second gluten-sensitive DQ genotype group (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, 30 DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half heterodimer, DQ2.2 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05, 35 wherein the first gluten-sensitive DQ genotype group has a more dysregulated genexpression than the third gluten-sensitive DQ genotype group, wherein more dysregulated genexpression is characterized by DFP-P04535WO10 Application (final).docx 78 at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are at least 50% more downregulated in the first gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 50% – 90%; and / or5 at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are at least 30% more upregulated in the first gluten-sensitiveDQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 33% – 100%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM210 (inflammation) are at least 50% more upregulated in the first gluten-sensitive DQgenotype group than in the third gluten-sensitive DQ genotype group, preferablybetween 50% – 100%; andwherein the second gluten-sensitive DQ genotype group has a more dysregulated genexpression than the third gluten-sensitive DQ genotype group, 15 wherein more dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are are between 10% – 49% more downregulated in thesecond gluten-sensitive DQ genotype group than in the third gluten-sensitive DQgenotype group; and / or20 at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are between 10% – 29% more upregulated in the secondgluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotypegroup, preferably between 12% – 25%; and / orat least one, preferably more than one of the genes STAT1, GBP1 and TGM225 (inflammation) are between 1% – 49% more upregulated in the second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 5% – 20%,wherein the TG2 inhibitor is a reversible TG2inhibitor or an irreversible TG2 inhibitor. 30 Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining a sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, 35 wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. DFP-P04535WO10 Application (final).docx 79 Preferably, wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or 5 wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or wherein a subject applying to (iii) is characterized by a villous height to crypt depth 10 (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. Preferred is a method, wherein the first gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than the15 third gluten-sensitive DQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by for transit amplifying cells, genes from the first gluten-sensitive DQ genotype group are on average at least 50% more upregulated than genes from20 the third gluten-sensitive DQ genotype group, and / or for mature enterocytes genes from the first gluten-sensitive DQ genotypegroup are on average at least 200% more downregulated than genes from the third gluten-sensitive DQ genotype group; and / or for immune cells, genes from the first gluten-sensitive DQ genotype group25 are on average at least 100% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the first gluten-sensitive DQgenotype group are on average at least 200% more upregulated than genes fromthe third gluten-sensitive DQ genotype group; 30 wherein the second gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than the third gluten-sensitiveDQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by 35 for transit amplifying cells, genes from the second gluten-sensitive DQ genotype group are on average at least 20% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or DFP-P04535WO10 Application (final).docx 80 for mature enterocytes, genes from the second gluten-sensitive DQgenotype group are on average at least 50% more downregulated than genesfrom the third gluten-sensitive DQ genotype group; and / or for immune cells, genes from the second gluten-sensitive DQ genotype5 group are on average at least 5% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the second gluten-sensitive DQgenotype group are on average at least 50% more upregulated than genes from the third gluten-sensitive DQ genotype group. 10 In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1). 15 Preferably, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the 20 treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,25 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,30 (ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- 35 specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and DFP-P04535WO10 Application (final).docx 81 (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, 5 of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic 10 measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, wherein for a subject applying to the first gluten-sensitive DQ genotype group (i) 15 the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering a more potent TG2 inhibitor than a therapeutic regimen for a subject applying to the second gluten-sensitive DQ genotype group (ii) or third gluten-sensitive DQ genotype group (iii),20 wherein the human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA- DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; 25 HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one30 copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO, wherein the first gluten-sensitive DQ genotype group has a more dysregulated genexpression than the third gluten-sensitive DQ genotype group, wherein more dysregulated genexpression is characterized by 35 at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are at least 50% more downregulated in the first gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 50% – 90%; and / orDFP-P04535WO10 Application (final).docx 82 at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are at least 30% more upregulated in the first gluten-sensitiveDQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 33% – 100%; and / or5 at least one, preferably more than one of the genes STAT1, GBP1 and TGM2 (inflammation) are at least 50% more upregulated in the first gluten-sensitive DQgenotype group than in the third gluten-sensitive DQ genotype group, preferablybetween 50% – 100%; andwherein the second gluten-sensitive DQ genotype group has a more dysregulated 10 genexpression than the third gluten-sensitive DQ genotype group, wherein more dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 (mature enterocytes) are are between 10% – 49% more downregulated in thesecond gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ15 genotype group; and / or at least one, preferably more than one of the genes AGR2, MKI167, and CENPF(cell proliferation) are between 10% – 29% more upregulated in the secondgluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotypegroup, preferably between 12% – 25%; and / or20 at least one, preferably more than one of the genes STAT1, GBP1 and TGM2 (inflammation) are between 1% – 49% more upregulated in the second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 5% – 20%,wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG225 inhibitor. Preferred is a method, wherein before step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining a sample of genetic material from said subject;30 (a’’) determining the human leukocyte antigen class II genotype of said subjectin said sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject. 35 Preferably, wherein a subject applying to (i) is characterized by a change of villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or DFP-P04535WO10 Application (final).docx 83 wherein a subject applying to (ii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.4 to -1.0 (-0.4 ≥ VH:CrD ratio > -1.0) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet, and / or 5 wherein a subject applying to (iii) is characterized by a villous height to crypt depth (VH:CrD) ratio between -0.1 to -0.4 (-0.1 ≥ VH:CrD ratio > -0.4) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. Preferred is a method, wherein the first gluten-sensitive DQ genotype group has a10 more dysregulated group of (at least two) genes of a biological pathway than thethird gluten-sensitive DQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathwayis characterized by for transit amplifying cells, genes from the first gluten-sensitive DQ15 genotype group are on average at least 50% more upregulated than genes fromthe third gluten-sensitive DQ genotype group, and / or for mature enterocytes genes from the first gluten-sensitive DQ genotypegroup are on average at least 200% more downregulated than genes from the third gluten-sensitive DQ genotype group; and / or20 for immune cells, genes from the first gluten-sensitive DQ genotype groupare on average at least 100% more upregulated than genes from the third gluten- sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the first gluten-sensitive DQgenotype group are on average at least 200% more upregulated than genes from25 the third gluten-sensitive DQ genotype group; wherein the second gluten-sensitive DQ genotype group has a more dysregulated group of (at least two) genes of a biological pathway than the third gluten-sensitiveDQ genotype group, wherein a more dysregulated group of (at least two) genes of a biological pathway30 is characterized by for transit amplifying cells, genes from the second gluten-sensitive DQ genotype group are on average at least 20% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for mature enterocytes, genes from the second gluten-sensitive DQ35 genotype group are on average at least 50% more downregulated than genesfrom the third gluten-sensitive DQ genotype group; and / or DFP-P04535WO10 Application (final).docx 84 for immune cells, genes from the second gluten-sensitive DQ genotypegroup are on average at least 5% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the second gluten-sensitive DQ5 genotype group are on average at least 50% more upregulated than genes from the third gluten-sensitive DQ genotype group. In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-yl-10 amino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Comp.1).The present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective 15 amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising:20 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to25 (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group,30 wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and35 (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, DFP-P04535WO10 Application (final).docx 85 of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor,an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 5 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject, 10 wherein step b) further comprises identifying said subject, at least based on the determined human leukocyte antigen DQ haplotypes of said subject, as applying to the first gluten-sensitive DQ genotype group, if the subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease. 15 Preferably, a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease is characterized by a changeof villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a20 comparative subject on gluten-free diet. The present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective 25 amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising:30 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as applying to35 (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,DFP-P04535WO10 Application (final).docx 86 wherein the first gluten-sensitive DQ genotype group has a stronger gluten- specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype group has a stronger gluten- specific T cell response than the third gluten-sensitive DQ genotype group, 5 wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to (encoding proteins for) mature enterocytes and / or cell proliferation and / or inflammation; and (c) selecting or adjusting a therapy regimen for said subject based on the DQgenotype group (i), (ii), or (iii) of said subject , 10 wherein one or more therapeutic measures comprising dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, duration of treatment, of the therapy regimen differ based on the DQ genotype group (i), (ii), or (iii) of said subject, with other words wherein the therapy regimen comprises one or moretherapeutic measures selected from a dose level of transglutaminase 2 inhibitor, 15 an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures20 based on the DQ genotype group of said subject, wherein a subject applying to the first gluten-sensitive DQ genotype group is a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease. 25 Preferably, a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease is characterized by a change of villousheight to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 30 Thus, the present invention relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the 35 treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: DFP-P04535WO10 Application (final).docx 87 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyte5 antigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject hasbeen identified having a risk for refractory coeliac diseases or suffering from refractory coeliac diseases , 10 wherein the therapy regimen comprises one or more therapeutic measures selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment. The present invention further relates to a computer-implemented method for 15 selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by 20 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject;25 (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject hasbeen identified having a risk for refractory coeliac diseases or suffering from30 refractory coeliac diseases, wherein the therapy regimen comprises one or more therapeutic measures selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment, wherein the therapy regimen comprises TG2 inhibitor at a daily dose between35 0.1 mg – 1000 mg, preferably between 0.5 mg – 500 mg, more preferably between0.75 mg – 250 mg, most preferably between 1 mg – 100 mg.DFP-P04535WO10 Application (final).docx 88 Preferably, a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease is characterized by a change of villousheight to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject 5 on gluten-free diet. The present invention further relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a 10 therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising:15 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory20 coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject hasbeen identified having a risk for refractory coeliac diseases or suffering from refractory coeliac diseases , wherein the therapy regimen comprises one or more therapeutic measures 25 selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment, wherein the therapy regimen comprises TG2 inhibitor at a daily dose between 25 mg – 1000 mg, preferably between 25 mg – 500 mg, more preferably between 25mg – 250 mg, most preferably between 30 mg – 100 mg.30 In some preferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose between 150 mg – 250 mg, more preferably between 160mg – 240 mg, more preferably between 170 mg – 230 mg, more preferablybetween 180 mg – 220 mg, more preferably between 190 mg – 210 mg. In some35 preferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose of (about) 200 mg. DFP-P04535WO10 Application (final).docx 89 Preferably, a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease is characterized by a changeof villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a 5 comparative subject on gluten-free diet. The present invention further relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a 10 therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising:15 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory20 coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject hasbeen identified having a risk for refractory coeliac diseases or suffering from refractory coeliac disease, wherein the therapy regimen comprises one or more therapeutic measures 25 selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment, wherein for a subject having a risk for refractory coeliac disease or suffering from refractory coeliac disease the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at 30 higher frequency, longer duration of treatment, administering a stronger TG2 inhibitor than a therapeutic regimen for a subject not suffering from refractory coeliac disease. Preferably, a subject having a risk for refractory coeliac disease or a subject35 suffering from refractory coeliac disease is characterized by a change of villousheight to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. DFP-P04535WO10 Application (final).docx 90 The present invention further relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a 5 therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising:10 (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory15 coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject hasbeen identified having a risk for refractory coeliac diseases or suffering from refractory coeliac disease, wherein the therapy regimen comprises one or more therapeutic measures 20 selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment, wherein the human leukocyte antigen DQ haplotypes include one or more ofHLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA-DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes. 25 Preferably, a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease is characterized by a change of villousheight to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject30 on gluten-free diet. The present invention further relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a 35 therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by DFP-P04535WO10 Application (final).docx 91 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyte5 antigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject has10 been identified having a risk for refractory coeliac diseases or suffering from refractory coeliac disease, wherein the therapy regimen comprises one or more therapeutic measures selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment, 15 wherein the therapy regimen comprises TG2 inhibitor at a daily dose between 0.1 mg – 1000 mg, preferably between 0.5 mg – 500 mg, most preferably between1 mg – 100 mg, preferably wherein the therapy regimen comprises TG2 inhibitor ata daily dose between 25 mg – 1000 mg, preferably between 25 mg – 500 mg,more preferably between 25 mg – 250 mg, most preferably between 30 mg – 10020 mg; wherein the human leukocyte antigen DQ haplotypes include one or more ofHLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA-DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes. 25 In some preferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose between 150 mg – 250 mg, more preferably between 160mg – 240 mg, more preferably between 170 mg – 230 mg, more preferablybetween 180 mg – 220 mg, more preferably between 190 mg – 210 mg. In somepreferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at30 a daily dose of (about) 200 mg. The present invention further relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a 35 therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by DFP-P04535WO10 Application (final).docx 92 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyte5 antigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject has10 been identified having a risk for refractory coeliac diseases or suffering from refractory coeliac disease, wherein the therapy regimen comprises one or more therapeutic measures selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment, 15 wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA-DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and 20 wherein the HLA-DQ8 haplotypes are selected from the group comprising or consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO. 25 Preferably, a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease is characterized by a changeof villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a30 comparative subject on gluten-free diet. The present invention further relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a 35 therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by DFP-P04535WO10 Application (final).docx 93 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise human leukocyte5 antigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject has10 been identified having a risk for refractory coeliac disease or suffering from refractory coeliac disease, wherein the therapy regimen comprises one or more therapeutic measures selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment, 15 wherein step b) further comprises identifying said subject as subject having a risk for refractory coeliac disease or suffering from refractory coeliac disease if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02. 20 Preferably, a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease is characterized by a change of villousheight to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 25 The present invention further relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the 30 treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,35 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; DFP-P04535WO10 Application (final).docx 94 (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject has5 been identified having a risk for refractory coeliac disease or suffering from refractory coeliac disease, wherein the therapy regimen comprises one or more therapeutic measures selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment, 10 wherein the therapy regimen comprises TG2 inhibitor at a daily dose between 0.1 mg – 1000 mg, preferably between 0.5 mg – 500 mg, most preferably between1 mg – 100 mg, preferably wherein the therapy regimen comprises TG2 inhibitor ata daily dose between 25 mg – 1000 mg, preferably between 25 mg – 500 mg,more preferably between 25 mg – 250 mg, most preferably between 30 mg – 10015 mg; wherein step b) further comprises identifying said subject as subject having a risk for refractory coeliac disease or suffering from refractory coeliac disease if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02. 20 In some preferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose between 150 mg – 250 mg, more preferably between 160mg – 240 mg, more preferably between 170 mg – 230 mg, more preferablybetween 180 mg – 220 mg, more preferably between 190 mg – 210 mg. In some25 preferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose of (about) 200 mg. Preferably, a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease is characterized by a change30 of villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. The present invention further relates to a computer-implemented method for 35 selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein DFP-P04535WO10 Application (final).docx 95 the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,5 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease;10 (c) selecting or adjusting a therapy regimen for said subject if the subject hasbeen identified having a risk for refractory coeliac disease or suffering from refractory coeliac disease, wherein the therapy regimen comprises one or more therapeutic measures selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor,15 type of TG2 inhibitor, and duration of treatment, wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG2 inhibitor. Preferably, a subject having a risk for refractory coeliac disease or a subject20 suffering from refractory coeliac disease is characterized by a change of villousheight to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 25 In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-yl- amino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Comp.1).The present invention further relates to a computer-implemented method for 30 selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by 35 administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,DFP-P04535WO10 Application (final).docx 96 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory 5 coeliac disease or a subject suffering from refractory coeliac disease; (c) selecting or adjusting a therapy regimen for said subject if the subject hasbeen identified having a risk for refractory coeliac disease or suffering from refractory coeliac disease, wherein the therapy regimen comprises one or more therapeutic measures 10 selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor, type of TG2 inhibitor, and duration of treatment, wherein the therapy regimen comprises TG2 inhibitor at a daily dose between 0.1 mg – 1000 mg, preferably between 0.5 mg – 500 mg, most preferably between1 mg – 100 mg, preferably wherein the therapy regimen comprises TG2 inhibitor at15 a daily dose between 25 mg – 1000 mg, preferably between 25 mg – 500 mg,more preferably between 25 mg – 250 mg, most preferably between 30 mg – 100mg; wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG2 inhibitor. 20 In some preferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose between 150 mg – 250 mg, more preferably between 160mg – 240 mg, more preferably between 170 mg – 230 mg, more preferablybetween 180 mg – 220 mg, more preferably between 190 mg – 210 mg. In some25 preferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose of (about) 200 mg. Preferably, a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease is characterized by a change of villous30 height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)-35 methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-yl- amino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Comp.1).DFP-P04535WO10 Application (final).docx 97 The present invention further relates to a computer-implemented method for selecting a therapy regimen for a subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the 5 treatment of the celiac disease of said subject, or formulated differently wherein the therapy regimen comprises at least the treatment of celiac disease by administering a therapeutically effective amount of at least one TG2 inhibitor to said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,10 wherein the human leukocyte antigen class II genotype comprise human leukocyteantigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined human leukocyteantigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or a subject suffering from refractory coeliac disease;15 (c) selecting or adjusting a therapy regimen for said subject if the subject hasbeen identified having a risk for refractory coeliac disease or suffering from refractory coeliac disease, wherein the therapy regimen comprises one or more therapeutic measures selected from dose level of TG2 inhibitor, administration interval of TG2 inhibitor,20 type of TG2 inhibitor, and duration of treatment, wherein the therapy regimen comprises TG2 inhibitor at a daily dose between 0.1 mg – 1000 mg, preferably between 0.5 mg – 500 mg, most preferably between1 mg – 100 mg, preferably wherein the therapy regimen comprises TG2 inhibitor ata daily dose between 25 mg – 1000 mg, preferably between 25 mg – 500 mg,25 more preferably between 25 mg – 250 mg, most preferably between 30 mg – 100mg; wherein the TG2 inhibitor is a reversible TG2 inhibitor or an irreversible TG2 inhibitor, wherein step b) further comprises 30 identifying said subject as subject having a risk for refractory coeliac disease or suffering from refractory coeliac disease if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02. In some preferred embodiments, the therapy regimen preferably comprises TG235 inhibitor at a daily dose between 150 mg – 250 mg, more preferably between 160mg – 240 mg, more preferably between 170 mg – 230 mg, more preferablybetween 180 mg – 220 mg, more preferably between 190 mg – 210 mg. In someDFP-P04535WO10 Application (final).docx 98 preferred embodiments, the therapy regimen preferably comprises TG2 inhibitor at a daily dose of (about) 200 mg. Preferably, a subject having a risk for refractory coeliac disease or a subject 5suffering from refractory coeliac disease is characterized by a change of villousheight to crypt depth (VH:CrD) ratio between -1.0 to -2.7 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet. 10 In particular preferred embodiments, the transglutaminase 2 inhibitor is (S,E)- methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1). 15 TG2 Inhibitor The TG2 inhibitor may be a reversible TG2 inhibitor or an irreversible TG2 inhibitor. In some preferred embodiments, the TG2 inhibitor is a reversible TG2inhibitor. In some preferred embodiments, the TG2 inhibitor is an irreversible TG2inhibitor. 20 Reversible TG2 Inhibitors 1) Reversible Inhibitors In some preferred embodiments the TG2 inhibitor is a reversible TG2 inhibitor. In some further preferred embodiments, the reversible TG2 inhibitor is a compound25 of the general formula (Irev): wherein L represents –L1– or –L1-L2–; preferably –L1-L2–; L1represents –CH2–, –CH2CH2–, –CH2CH2CH2–, –CH2CO–, or –CH2CH2CO–; 30 L2represents a bond, –NRN1–, –NRN1CH2–, –NRN1CH2CH2–, or –NRN1CH(CH3)–; DFP-P04535WO10 Application (final).docx 99 5 10 DFP-P04535WO10 Application (final).docx 100 ,, , ,, , ,, ,, ,, , ,, , ,DFP-P04535WO10 Application (final).docx 101 DFP-P04535WO10 Application (final).docx 102 DFP-P04535WO10 Application (final).docx 103 wherein the unsubstituted bicyclic residues can be substituted with 1 to 5 of the substituents R9 – R14 and RN ; and preferably with 1 to 3 of the substituents R11 –R13; 5 R3represents bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.2]nonyl, bicyclo[3.3.2]decyl, bicyclo[3.3.3]undecyl, 4-homoisotwistyl, adamantyl, diamantyl, hexamethylenetetraminyl and the afore-mentioned residues optionally contain one 10 or more C=C double bond(s) and / or are optionally substituted by one or more of Ra, Rb, Rc, Rd, and Re; Ra, Rb, Rc, Rd, and Rerepresent independently of each other –H, –F, –Cl, –Br, –CN, –OH, –CH3, –CH2CH3, –CH2CH2CH3, –CH(CH3)2, –CHF2, –CF3, 15 –CH2CF3, –COCH3, –COCH2CH3, –CO2H, –CO2CH3, –CO2C2H5, –CONH2, –CONHCH3, –CON(CH3)2, –CONHC2H5, –CH2CO2H, –CH2CO2CH3, –CH2CO2C2H5, –CH2CONH2, –CH2CONHCH3, –CH2CON(CH3)2, –CH2CONHC2H5, –NHCOCH3, –NHCOC2H5, –NHCOCF3, –NHCOCH2CF3, –NHSO2CH3, –NHSO2C2H5, –NHSO2CHF2, –NHSO2CF3, or –NHSO2CH2CF3; 20 R4represents –NR6R7; R6and R7represent independently of each other –H, –CH3, –CH2CH3, 25 –CH2CH=C(CH3)2, –CH2CH=CHCH2CH3, –cyclo-C3H5, –cyclo-C4H7, DFP-P04535WO10 Application (final).docx 104 –cyclo-C5H9, –cyclo-C6H11, –CH2–cyclo-C3H5, –CH2–cyclo-C4H7, –CH2–cyclo- C5H9, –CH2–cyclo-C6H11, –Ph, –CH2–Ph, –CH2OCH3, –CH2OCH2CH3, –CH2CH2OCH3, –CH2CH2OCH2CH3, –CH2CH2NHCH3, or –CH2CH2N(CH3)2, or –NR6R7 is –N(C2H5)2, 5 R8, R9, R10, R11, R12, R13, and R14represent independently of each other –H, –F, –Cl, –Br, –I, –OH, ^CN, –NO2, ^CH3, ^C2H5, ^C3H7, ^CH(CH3)2, ^C4H9, ^CH2^CH(CH3)2, ^CH(CH3)^C2H5,^C(CH3)3, ^cyclo-C3H5, ^CH2^cyclo^C3H5, –CH2OH, ^CH2F, ^CHF2, ^CF3, ^CH2Cl, 10 ^CH2Br, ^CH2I, ^CH2^CH2F, ^CH2^CHF2, ^CH2^CF3, ^CH2^CH2Cl, ^CH2^CH2Br, ^CH2^CH2I, –OCH3, –OC2H5, –OC3H7, –OCH(CH3)2, –OC(CH3)3, –OC4H9, –OCHF2, –OCF3, −OCH2CF3, –OC2F5, −OCH2OCH3, –O-cyclo-C3H5, –OCH2-cyclo-C3H5, –O–C2H4-cyclo-C3H5, –CHO, –COCH3, –COCF3, –COC2H5, –COC3H7, –COCH(CH3)2, –COC(CH3)3, 15 –COOH, –COOCH3, –COOC2H5, –COOC3H7, –COOCH(CH3)2, –COOC(CH3)3, –OOC–CH3, –OOC–CF3, –OOC–C2H5, –OOC–C3H7, –OOC–CH(CH3)2, –OOC–C(CH3)3, –NH2, –NHCH3, –NHC2H5, –NHC3H7, –NHCH(CH3)2, –NHC(CH3)3, –N(CH3)2, –N(C2H5)2, –N(C3H7)2, –N[CH(CH3)2]2, –N[C(CH3)3]2, –NHCOCH3, –NHCOCF3, –NHCOC2H5, –NHCOC3H7, –NHCOCH(CH3)2, 20 –NHCOC(CH3)3, –CONH2, –CONHCH3, –CONHC2H5, –CONHC3H7, –CONHCH(CH3)2, –CONH^cyclo-C3H5, –CONHC(CH3)3, –CON(CH3)2, –CON(C2H5)2, –CON(C3H7)2, –CON[CH(CH3)2]2, –CON[C(CH3)3]2, –SO2NH2, –SO2NHCH3, –SO2NHC2H5, –SO2NHC3H7, –SO2NHCH(CH3)2, –SO2NH^cyclo-C3H5, –SO2NHC(CH3)3, –SO2N(CH3)2, –SO2N(C2H5)2, 25 30 or R8and R9or R9and R10can form together one of the following five- membered or six-membered rings: DFP-P04535WO10 Application (final).docx 105 , or R12and R13or R13and R14can form together one of the following five- 5 membered or six-membered rings: RNrepresents –H, ^CH3, ^C2H5, ^C3H7, ^CH(CH3)2, ^C4H9, ^CH2^CH(CH3)2, ^CH(CH3)^C2H5, ^C(CH3)3, ^cyclo-C3H5, ^cyclo-C4H7, 10 ^cyclo-C5H9, ^CH2^cyclo^C3H5, ^CH2^cyclo-C4H7, ^CH2^cyclo-C5H9, ^CH2F, ^CHF2, ^CF3, ^CH2Cl, ^CH2Br, ^CH2I, ^CH2^CH2F, ^CH2^CHF2, ^CH2^CF3, ^CH2^CH2Cl, ^CH2^CH2Br, ^CH2^CH2I, ^CH2^CH=CH2, ^CH2-C≡CH, –CHO, –COCH3, –COC2H5, –COC3H7, –COCH(CH3)2, –COC(CH3)3, ^CO^cyclo^C3H5, ^CO^cyclo-C4H7, ^CO^cyclo-C5H9, –COOCH3, 15 –COOC2H5, –COOC3H7, –COOCH(CH3)2, –COOC(CH3)3, –COOCH2Ph, –SO2CH3, –SO2CF3, –SO2C2H5, –SO2C3H7, –SO2CH(CH3)2, –SO2^cyclo^C3H5, or –SO2C(CH3)3; RN1represents –H, –CH3, or –CH2CH3; 20 or a diastereomer, an enantiomer, a mixture of diastereomers, a mixture of enantiomers, a racemate, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof. 25 More preferably, the reversible TG2 inhibitor is a compound of the general formula (Irev), wherein R2represents , , DFP-P04535WO10 Application (final).docx 106 5 DFP-P04535WO10 Application (final).docx 107 DFP-P04535WO10 Application (final).docx 108 ,, ,,, ,,,, ,,, , , , ,, , , , ,DFP-P04535WO10 Application (final).docx 109 wherein the unsubstituted bicyclic residues can be substituted with 1 to 5 of the substituents R9 – R14 and RN ; and preferably with 1 to 3 of the substituents R11 –R13 and the substituents R9 – R14 and RN have the meanings as defined herein for5 compound of general formula (Irev). DFP-P04535WO10 Application (final).docx 110 More preferably, the reversible TG2 inhibitor is a compound of the general formula (Irev), wherein R2represents 5 10 DFP-P04535WO10 Application (final).docx 111 , , wherein the unsubstituted bicyclic residues can be substituted with 1 to 5 of the substituents R9 – R14 and RN ; and preferably with 1 to 3 of the substituents R11 –R13 and the substituents R9 – R14 and RN have the meanings as defined herein fora compound of the general formula (Irev). 5 More preferably, the reversible TG2 inhibitor is a compound of the general formula (Irev), wherein the compound has the formula (Ibrev) wherein 10 L represents –L1– or –L1-L2–; preferably –L1-L2–; L1represents –CH2–, –CH2CH2–, –CH2CH2CH2–, –CH2CO–, or –CH2CH2CO–; L2represents a bond, –NRN1–, –NRN1CH2–, –NRN1CH2CH2–, or –NRN1CH(CH3)–; DFP-P04535WO10 Application (final).docx 112 5 10 , DFP-P04535WO10 Application (final).docx 113 R3represents bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, 5 bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.2]nonyl, bicyclo[3.3.2]decyl, bicyclo[3.3.3]undecyl, 4-homoisotwistyl, adamantyl, diamantyl, hexamethylenetetraminyl, and the afore-mentioned residues optionally contain one or more C=C double bond(s) and / or are substituted by one or more of Ra, Rb, Rc, Rd, and Re; 10 Ra, Rb, Rc, Rd, and Rerepresent independently of each other –H, –F, –Cl, –Br, –CN, –OH, –CH3, –CH2CH3, –CH2CH2CH3, –CH(CH3)2, –CHF2, –CF3, –CH2CF3, –COCH3, –COCH2CH3, –CO2H, –CO2CH3, –CO2C2H5, –CONH2, –CONHCH3, –CON(CH3)2, –CONHC2H5, –CH2CO2H, –CH2CO2CH3, 15 –CH2CO2C2H5, –CH2CONH2, –CH2CONHCH3, –CH2CON(CH3)2, –CH2CONHC2H5, –NHCOCH3, –NHCOC2H5, –NHCOCF3, –NHCOCH2CF3, –NHSO2CH3, –NHSO2C2H5, –NHSO2CHF2, –NHSO2CF3, or –NHSO2CH2CF3; R4represents –NR6R7; 20 R6and R7represent independently of each other –H, –CH3, –CH2CH3, –CH2CH2CH3, –CH(CH3)2, –CH2CH2CH2CH3, –CH2CH2CH2CH2CH3, –CH2CH(CH3)2, –C(CH3)3, –CH2CH=CH2, –CH2CH=CH(CH3), –CH2CH=C(CH3)2, –CH2CH=CHCH2CH3, –cyclo-C3H5, –cyclo-C4H7,25 –cyclo-C5H9, –cyclo-C6H11, –CH2–cyclo-C3H5, –CH2–cyclo-C4H7, –CH2–cyclo- C5H9, –CH2–cyclo-C6H11, –Ph, –CH2–Ph, –CH2OCH3, –CH2OCH2CH3, –CH2CH2OCH3, –CH2CH2OCH2CH3, –CH2CH2NHCH3, –CH2CH2N(CH3)2, 30 RNrepresents –H, ^CH3, ^C2H5, ^C3H7, ^CH(CH3)2, ^C4H9, ^CH2^CH(CH3)2, ^CH(CH3)^C2H5, ^C(CH3)3, ^cyclo-C3H5, ^cyclo-C4H7, ^cyclo-C5H9, ^CH2^cyclo^C3H5, ^CH2F, ^CHF2, ^CF3, ^CH2Cl, ^CH2Br, ^CH2I, ^CH2^CH2F, ^CH2^CHF2, ^CH2^CF3, ^CH2^CH2Cl, ^CH2^CH2Br, DFP-P04535WO10 Application (final).docx 114 ^CH2^CH2I, ^CH2^CH=CH2, ^CH2-C≡CH, –CHO, –COCH3, –COC2H5, –COC3H7, –COCH(CH3)2, –COC(CH3)3, –COOCH3, –COOC2H5, –COOC3H7, –COOCH(CH3)2, –COOC(CH3)3, –COOCH2Ph, –SO2CH3, –SO2CF3, –SO2C2H5, –SO2C3H7, –SO2CH(CH3)2, or –SO2C(CH3)3; 5 RN1represent –H, –CH3, or –CH2CH3; and R8 – R14 have the meanings as defined in formula (Irev);or a diastereomer, an enantiomer, a mixture of diastereomers, a mixture of enantiomers, a racemate, a solvate, a hydrate, or a pharmaceutically acceptable10 salt thereof. More preferably, the reversible TG2 inhibitor is a compound of the general formula (Irev), wherein L1represents –CH2–, or –CH2CO–; 15 L2represents a bond, –NRN1–, –NRN1CH2–, or –NRN1CH(CH3)–; R3represents bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, 4-homoisotwistyl, adamantyl, or diamantyl, and the afore-mentioned residues optionally contain one or more C=C double bond(s) and / or are substituted by one or more of Ra, Rb, Rc, Rd, and Re; 20 and Ra, Rb, Rc, Rd, Reand RN1have the same meanings as defined herein for compound of the general formula (Irev). More preferably, the reversible TG2 inhibitor is a compound of the general formula (Irev), wherein R2represents 25 , DFP-P04535WO10 Application (final).docx 115 5 general formula (Irev). More preferably, the reversible TG2 inhibitor is a compound of the general formula (Irev), wherein the compound has any one of the formulae (IV-arev) – (IV-orev) and(V-arev) – (V-drev):10 DFP-P04535WO10 Application (final).docx 116 (V-crev) DFP-P04535WO10 Application (final).docx 117 have the samemeanings as defined herein for a reversible TG2 inhibitor is a compound of the general formula (Irev). 5 More preferably, the reversible TG2 inhibitor is a compound of the general formula (Irev), wherein R2represents 10 , DFP-P04535WO10 Application (final).docx 118 5 10 DFP-P04535WO10 Application (final).docx 119 R6represents –H, –CH3, –CH2CH3, –CH(CH3)2, –CH2CH2CH3, –CH2CH=CH2, –CH2CH2CH2CH3, –CH2CH(CH3)2, –C(CH3)3, –CH2CH2CH2CH2CH3, –cyclo-C3H5, –cyclo-C5H9, –cyclo-C6H11 or –CH2–cyclo-C3H5. 5 In some preferred embodiments, the reversible TG2 inhibitor is a compound of the general formula (Irev) selected from the group consisting of: DFP-P04535WO10 Application (final).docx 120 DFP-P04535WO10 Application (final).docx 121 DFP-P04535WO10 Application (final).docx 122 DFP-P04535WO10 Application (final).docx 123 DFP-P04535WO10 Application (final).docx 124 DFP-P04535WO10 Application (final).docx 125 DFP-P04535WO10 Application (final).docx 126 DFP-P04535WO10 Application (final).docx 127 DFP-P04535WO10 Application (final).docx 128 DFP-P04535WO10 Application (final).docx 129 DFP-P04535WO10 Application (final).docx 130 DFP-P04535WO10 Application (final).docx 131 or a pharmaceutically acceptable salt thereof. In some other preferred embodiments, the reversible TG2 inhibitor is a compound of the general formula (Irev) selected from the group consisting of: DFP-P04535WO10 Application (final).docx 132 DFP-P04535WO10 Application (final).docx 133 DFP-P04535WO10 Application (final).docx 134 DFP-P04535WO10 Application (final).docx 135 DFP-P04535WO10 Application (final).docx 136 DFP-P04535WO10 Application (final).docx 137 DFP-P04535WO10 Application (final).docx 138 DFP-P04535WO10 Application (final).docx 139 DFP-P04535WO10 Application (final).docx 140 DFP-P04535WO10 Application (final).docx 141 or a pharmaceutically acceptable salt thereof. Irreversible TG2 Inhibitors 5 1) Irreversible Inhibitors In some preferred embodiments the TG2 inhibitor is an irreversible TG2 inhibitor. In some further preferred embodiments, the irreversible TG2 inhibitor is compound of the general formula (Iirr): 10 wherein E1, E2represent independently of each other –CO– or –SO2–, R* represents one of the following rests –H, ^CH3, ^C2H5, ^C3H7,15 ^CH(CH3)2or ^C4H9, R#represents one of the following rests –NYY’, ^OH, ^OY, –NH–CH2–COOH, –NH–CH(CH3)–COOH, –NH–CH(CH2CH2SCH3)–COOH, –NH–CH(CH2OH)– COOH, –NH–CH(CH2SH)–COOH, –NH–CH(CH2CONH2)–COOH, 20 –NH–CH(CH2CH2CONH2)–COOH, , –NH–CH(CH2CH(CH3)2)–CH2COOH, –NH–CH(CH2Ph)–COOH, –NH–CH(CH2COOH)–COOH, –NH–CH(CH2CH2COOH)–COOH, –NH–CH(COOH)–CH(CH3)2, –NH–CH(COOH)–CH2CH(CH3)2, –NH–CH2–COOY’, –NH–CH(CH3)–COOY’, –NH–CH(CH2CH2SCH3)–COOY’, –NH–CH(CH2OH)–COOY’, 25 –NH–CH(CH2SH)–COOY’, –NH–CH(CH2CONH2)–COOY’, –NH–CH(CH2CH2CONH2)–COOY’, –NH–CH(CH2CH(CH3)2)–CH2COOY’, –NH– CH(CH2Ph)–COOY’, –NH–CH(CH2COOH)–COOY’, –NH–CH(CH2COOY’)– DFP-P04535WO10 Application (final).docx 142 DFP-P04535WO10 Application (final).docx 143 Yrepresents one of the following residues:–CH2R1, –CHR1–CH2R2, –CHR1–CHR2–CH2R3, –CHR1–CHR2–CHR3–CH2R4, –CHR1–CHR2–CHR3–CHR4–CH2R5, –CHR1–CHR2–CHR3–CHR4–CHR5–CH2R65 Y’, R17to R20are selected independently of each other from: –H, ^CH3, ^C2H5, ^C3H7, ^CH(CH3)2, ^C4H9, ^CH2^CH(CH3)2, ^CH(CH3)^C2H5, ^C(CH3)3, ^C5H11, ^CH(CH3)–C3H7, –CH2–CH(CH3)–C2H5, –CH(CH3)–CH(CH3)2, –C(CH3)2–C2H5, –CH2–C(CH3)3, –CH(C2H5)2 and –C2H4–CH(CH3)2;10 X represents –CR7R8R9, –CH2R7, –CHR7–CH2R8, –O–CH2R7, –O–CR7R8R9,–O–CHR7–CH2R8 DFP-P04535WO10 Application (final).docx 144 DFP-P04535WO10 Application (final).docx 145 ,DFP-P04535WO10 Application (final).docx 146 7 DFP-P04535WO10 Application (final).docx 147 7 , , ,Z represents: ^CH3, –C2H5, ^C3H7, –CH(CH3)2, ^C4H9, ^Ph, ^CH2^Ph,–OCH3, –OC2H5, –OC3H7, –OCH(CH3)2, –OC4H9, ^OPh, ^OCH2^Ph, ^OCH=CH2 or ^OCH2^CH=CH2; 5 R1to R10represent independently of each other the following groups: –H, –OH, –OCH3, –OC2H5, –OC3H7, –O–cyclo-C3H5, –OCH(CH3)2, –OC(CH3)3, –OC4H9, ^OPh, ^OCH2^Ph, ^OCPh3, –SH, –NO2, –F, –Cl, –Br, –I, –N3, –CN, –OCN, –NCO, –SCN, –NCS, –CHO, –COCH3, 10 –COC2H5, –COC3H7, –CO–cyclo-C3H5, –COCH(CH3)2, –COC(CH3)3, –COOH, –COCN, –COOCH3, –COOC2H5, –COOC3H7, –COO–cyclo-C3H5, –COOCH(CH3)2, –COOC(CH3)3, –CONH2, –CONHCH3, –CONHC2H5, –CONHC3H7, –CONH–cyclo-C3H5, –CONH[CH(CH3)2], –CONH[C(CH3)3], –CON(CH3)2, –CON(C2H5)2, –CON(C3H7)2, –CON(cyclo-C3H5)2, 15 –CON[CH(CH3)2]2, –CON[C(CH3)3]2, –NHCOCH3, –NHCOC2H5, –NHCOC3H7, –NHCO–cyclo-C3H5, –NHCO–CH(CH3)2, –NHCO–C(CH3)3, –NHCO–OCH3, –NHCO–OC2H5, –NHCO–OC3H7, –NHCO–O–cyclo-C3H5, –NHCO–OCH(CH3)2, –NHCO–OC(CH3)3, –NH2, –NHCH3, –NHC2H5, –NHC3H7, –NH–cyclo-C3H5, –NHCH(CH3)2, –NHC(CH3)3, –N(CH3)2, 20 –N(C2H5)2, –N(C3H7)2, –N(cyclo-C3H5)2, –N[CH(CH3)2]2, –N[C(CH3)3]2, –SOCH3, –SOC2H5, –SOC3H7, –SO–cyclo-C3H5, –SOCH(CH3)2, –SOC(CH3)3, –SO2CH3, –SO2C2H5, –SO2C3H7, –SO2–cyclo-C3H5, –SO2CH(CH3)2, –SO2C(CH3)3, –SO3H, –SO3CH3, –SO3C2H5, –SO3C3H7, –SO3–cyclo-C3H5, –SO3CH(CH3)2, –SO3C(CH3)3, –SO2NH2, –OCF3, –OC2F5, DFP-P04535WO10 Application (final).docx 148 –O–COOCH3, –O–COOC2H5, –O–COOC3H7, –O–COO–cyclo-C3H5, –O–COOCH(CH3)2, –O–COOC(CH3)3, –NH–CO–NH2, –NH–CO–NHCH3, –NH–CO–NHC2H5, –NH–CO–NHC3H7, –NH–CO–NH–cyclo-C3H5, –NH–CO–NH[CH(CH3)2], –NH–CO–NH[C(CH3)3], –NH–CO–N(CH3)2, 5 –NH–CO–N(C2H5)2, –NH–CO–N(C3H7)2, –NH–CO–N(cyclo-C3H5)2, –NH–CO–N[CH(CH3)2]2, –NH–CO–N[C(CH3)3]2, –NH–CS–NH2, –NH–CS–NHCH3, –NH–CS–NHC2H5, –NH–CS–NHC3H7, –NH–CS–NH–cyclo-C3H5, –NH–CS–NH[CH(CH3)2], –NH–CS–NH[C(CH3)3], –NH–CS–N(CH3)2, –NH–CS–N(C2H5)2, –NH–CS–N(C3H7)2, 10 –NH–CS–N(cyclo-C3H5)2, –NH–CS–N[CH(CH3)2]2, –NH–CS–N[C(CH3)3]2, –NH2*HOOCCF3, ^CH2F, ^CF2Cl, ^CHF2, ^CF3, ^CH2Cl, ^CH2Br, ^CH2I, ^CH2^CH2F, ^CH2^CHF2, ^CH2^CF3, ^CH2^CH2Cl, ^CH2^CH2Br, ^CH2^CH2I, cyclo-C3H5, cyclo-C4H7, cyclo-C5H9, cyclo-C6H11, cyclo-C7H13, cyclo-C8H15, ^Ph, ^CH2^Ph, ^CPh3, 15 20 25 30 DFP-P04535WO10 Application (final).docx 149 ,DFP-P04535WO10 Application (final).docx 150 DFP-P04535WO10 Application (final).docx 151 , DFP-P04535WO10 Application (final).docx 152 ,, ,, N N N N N N N NN N N N N, , ,, N N N N N N N N N N N N N ,,N,, DFP-P04535WO10 Application (final).docx 153 90 ,, , ;the rests R11to R16represent independently of each other the following groups: –H, –NH2, –OH, –OCH3, –OC2H5, –OC3H7, –OCF3, ^CF3, –F, –Cl, –Br, –I, ^CH3, ^C2H5, ^C3H7, ^CH(CH3)2, ^Ph and –CN; 5 as well as stereoisomeric forms, E / Z isomers, enantiomers, mixtures of enantiomers, diastereomers, mixtures of diastereomers, racemates, tautomers, anomers, keto-enol-forms, betaine forms, prodrugs, solvates, hydrates, and pharmaceutically acceptable salts of the above mentioned compounds. 10 In some further preferred embodiments, the irreversible TG2 inhibitor is compound of the general formula (Iirr), wherein DFP-P04535WO10 Application (final).docx 154 Zrepresents –OCH3, –OCH2CH3, –OCH(CH3)2 or ^OCH2^Ph,R* represents one of the following rests: ^H or ^CH3,R#represents –NHY, Yhas the meaning as defined herein for a compound of the general formula (Iirr).5 More preferably, the irreversible TG2 inhibitor is a compound of the generalformula (Iirr), wherein Yrepresents –CH2R1, –CHR1–CH2R2, –CHR1–CHR2–CH2R3,–CHR1–CHR2–CHR3–CH2R4or –CHR1–CHR2–CHR3–CHR4–CH2R5and10 R1 to R5 represent independently of each other:–COOH, –COOCH3, –N(CH3)2, –N(C2H5)2, ^Ph, ^CH3, ^C2H5, ^CH2^CH(CH3)2, ^C(CH3)3, , , More preferably, the irreversible TG2 inhibitor is a compound of the general15 formula (Iirr), wherein Yrepresents ^CH3, , .–CH(CH3)–CH2–CH(CH3)2, –CH2–CH(C2H5)2, –CH2–CH(CH3)–C2H5, –C2H4–C(CH3)3or –C2H4–CH(C2H5)2. 20 More preferably, the irreversible TG2 inhibitor is a compound of the general formula (Iirr), wherein . DFP-P04535WO10 Application (final).docx 155 More preferably, the irreversible TG2 inhibitor is a compound of the general formula (Iirr), wherein Zrepresents –OCH3, –OCH2CH3 or ^OCH2^Ph,5 E1represents –CO– or –SO2–, E2represents –CO– R* represents one of the following rests: ^H or ^CH3,R#represents one of the following rests: –NYY’,10 R1 to R5 represent independently of each other: –H, ^CH3, ^C2H5, ^Ph,^CH2^CH(CH3)2, –N(CH3)2, –N(C2H5)2, –COOH, –COOCH3, ^C(CH3)3, , ; R11 to R13 represent independently of each other –H, ^CH3, –C2H5 or ^CF3,15 R19is –C2H5, Xrepresents –CH2R7, –CHR7–CH2R8, –O–CH2R7,DFP-P04535WO10 Application (final).docx 156 R7 to R10 represent independently of each other –H, –OH, –COOH, –SO2NH2,^CH3, ^CF3, –NH–CO–NH2, –NH2*HOOCCF3or –NH2, , R14 to R16 represent independently of each other –H, –Cl or ^CH3, andR17and R20represent ^CH3. 5 More preferably, the irreversible TG2 inhibitor is a compound of the general formula (IIirr), wherein wherein X, Y and Z have the meaning as defined herein for a compound of thegeneral formula (Iirr). 10 DFP-P04535WO10 Application (final).docx 157 In some embodiment the irreversible TG2 inhibitor is selected from the group consisting of: (S,E)-ethyl 6-(benzyloxycarbonylamino)-7-oxo-7-(2-oxo-1-(2-oxo-2-(2,4,6- trimethylphenethylamino)ethyl)-1,2-dihydropyridin-3-ylamino)hept-2-enoate (S,E)-ethyl 6-(benzyloxycarbonylamino)-7-(1-(2-(isopentylamino)-2-oxoethyl)-6- methyl-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 6-(benzyloxycarbonylamino)-7-(1-(2-(isopentylamino)-2-oxoethyl)-2- oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-6-methyl-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate 3-(2-(3-((S,E)-2-(benzyloxycarbonylamino)-7-ethoxy-7-oxohept-5-enamido)-6- methyl-2-oxopyridin-1(2H)-yl)acetamido)-5-methylhexanoic acid (S,E)-isopropyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-di- hydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 7-(6-methyl-2-oxo-1-(2-oxo-2-(phenethylamino)ethyl)-1,2- dihydropyridin-3-ylamino)-6-(nicotinamido)-7-oxohept-2-enoate (S,E)-ethyl 6-((4-chlorophenyl)methylsulfonamido)-7-(1-(2-(isopentylamino)-2- oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 6-benzamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 6-(furan-3-carboxamido)-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo- 1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-7-oxo-6-(thiophene-3-carboxamido)hept-2-enoate (S,E)-ethyl 6-(furan-3-sulfonamido)-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-7-oxo-6-(4-sulfamoylbenzamido)hept-2-enoate (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(5-methylthiazole-4-carboxamido)-7-oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(nicotinamido)-7-oxohept-2-enoate (S,E)-ethyl 6-(3,5-bis(trifluoromethyl)benzamido)-7-(1-(2-(isopentylamino)-2- oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate DFP-P04535WO10 Application (final).docx 158 (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-7-oxo-6-(4-(piperidin-1-yl)benzamido)hept-2-enoate (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(4-(4-methylpiperazin-1-yl)benzamido)-7-oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-carboxamido)-7- oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-7-oxo-6-(phenylsulfonamido)hept-2-enoate (S,E)-5-(N-(7-ethoxy-1-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin- 3-ylamino)-1,7-dioxohept-5-en-2-yl)sulfamoyl)-2-hydroxybenzoic acid (S,E)-4-(7-ethoxy-1-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-1,7-dioxohept-5-en-2-ylamino)-4-oxobutanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-(2-(diethylamino)ethylamino)-2-oxoethyl)-2-oxo- 1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-4-(1-(1-(2-(2-(diethylamino)ethylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin- 3-ylamino)-7-ethoxy-1,7-dioxohept-5-en-2-ylamino)-4-oxobutanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-(2-(dimethylamino)ethylamino)-2-oxoethyl)-2-oxo- 1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-methyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-methyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-4-(7-ethoxy-1-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin- 3-ylamino)-1,7-dioxohept-5-en-2-ylamino)-4-oxobutanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-((S)-1-methoxy-4-methyl-1-oxopentan-2-ylamino)- 2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate 4-((S,E)-7-ethoxy-1-(1-(2-((S)-1-methoxy-4-methyl-1-oxopentan-2-ylamino)-2- oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-1,7-dioxohept-5-en-2-ylamino)-4- oxobutanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-((R)-1-methoxy-4-methyl-1-oxopentan-2-ylamino)- 2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate 4-((S,E)-7-ethoxy-1-(1-(2-((R)-1-methoxy-4-methyl-1-oxopentan-2-ylamino)-2- oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-1,7-dioxohept-5-en-2-ylamino)-4- DFP-P04535WO10 Application (final).docx 159 oxobutanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-((2S,3R)-1-methoxy-3-methyl-1-oxopentan-2- ylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate 4-((S,E)-7-ethoxy-1-(1-(2-((2S,3R)-1-methoxy-3-methyl-1-oxopentan-2-ylamino)-2- oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-1,7-dioxohept-5-en-2-ylamino)-4- oxobutanoic acid (S,E)-4-(7-ethoxy-1,7-dioxo-1-(2-oxo-1-(2-oxo-2-(4- (trifluoromethyl)benzylamino)ethyl)-1,2-dihydropyridin-3-ylamino)hept-5-en-2- ylamino)-4-oxobutanoic acid (S,E)-4-(1-(1-(2-(3,3-dimethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-7-ethoxy-1,7-dioxohept-5-en-2-ylamino)-4-oxobutanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-(3,3-dimethylbutylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 6-acetamido-7-(1-(2-((S)-1-methoxy-4,4-dimethyl-1-oxopentan-2- ylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate 4-((S,E)-7-ethoxy-1-(1-(2-((S)-1-methoxy-4,4-dimethyl-1-oxopentan-2-ylamino)-2- oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-1,7-dioxohept-5-en-2-ylamino)-4- oxobutanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-(3-ethylpentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-4-(7-ethoxy-1-(1-(2-(3-ethylpentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-1,7-dioxohept-5-en-2-ylamino)-4-oxobutanoic acid (S,E)-4-(7-ethoxy-1,7-dioxo-1-(2-oxo-1-(2-oxo-2-(2- (trifluoromethyl)benzylamino)ethyl)-1,2-dihydropyridin-3-ylamino)hept-5-en-2- ylamino)-4-oxobutanoic acid (S,E)-4-(7-ethoxy-1,7-dioxo-1-(2-oxo-1-(2-oxo-2-(4-(trifluoromethyl)piperidine-1- yl)ethyl)-1,2-dihydropyridin-3-ylamino)hept-5-en-2-ylamino)-4-oxobutanoic acid (S,E)-ethyl 6-acetamido-7-oxo-7-(2-oxo-1-(2-oxo-2-(2-(pyrrolidine-1- yl)ethylamino)ethyl)-1,2-dihydropyridin-3-ylamino)hept-2-enoate (S,E)-4-(7-ethoxy-1,7-dioxo-1-(2-oxo-1-(2-oxo-2-(2-(thiophen-2- yl)ethylamino)ethyl)-1,2-dihydropyridin-3-ylamino)hept-5-en-2-ylamino)-4- oxobutanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-((1-ethylpiperidin-4-yl)methylamino)-2-oxoethyl)-2- oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-4-(7-ethoxy-1,7-dioxo-1-(2-oxo-1-(2-oxo-2-(2-(2-oxoimidazolidin-1- yl)ethylamino)ethyl)-1,2-dihydropyridin-3-ylamino)hept-5-en-2-ylamino)-4- DFP-P04535WO10 Application (final).docx 160 oxobutanoic acid (6S,E)-ethyl 6-acetamido-7-(1-(2-(2-methylbutylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate 4-((2S,E)-7-ethoxy-1-(1-(2-(2-methylbutylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-1,7-dioxohept-5-en-2-ylamino)-4-oxobutanoic acid (6S,E)-ethyl 6-acetamido-7-(1-(2-(3-methylpiperidin-1-yl)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (2S,3R)-2-(2-(3-((S,E)-7-ethoxy-2-(1-methyl-1H-imidazole-5-carboxamido)-7- oxohept-5-enamido)-2-oxopyridin-1(2H)-yl)acetamido)-3-methylpentanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-(isobutylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (6S,E)-ethyl 6-acetamido-7-(1-(2-(3-methylbutan-2-ylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-7-oxo-6-(3-ureidopropanamido)hept-2-enoate (S,E)-ethyl 6-acetamido-7-(1-(2-((S)-1-methoxy-3-methyl-1-oxobutan-2-ylamino)-2- oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (2S,3R)-2-(2-(3-((S,E)-2-benzamido-7-ethoxy-7-oxohept-5-enamido)-2-oxopyridin- 1(2H)-yl)acetamido)-3-methylpentanoic acid (2S,3R)-2-(2-(3-((S,E)-7-methoxy-2-(1-methyl-1H-imidazole-5-carboxamido)-7- oxohept-5-enamido)-2-oxopyridin-1(2H)-yl)acetamido)-3-methylpentanoic acid (2S,3R)-2-(2-(3-((S,E)-2-benzamido-7-methoxy-7-oxohept-5-enamido)-2- oxopyridin-1(2H)-yl)acetamido)-3-methylpentanoic acid (S,E)-ethyl 6-acetamido-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-methyl 7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (6S,E)-methyl 6-acetamido-7-(1-(2-(3-methylpiperidin-1-yl)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-methyl 6-acetamido-7-oxo-7-(2-oxo-1-(2-oxo-2-(4-(trifluoromethyl)piperidin-1- yl)ethyl)-1,2-dihydropyridin-3-ylamino)hept-2-enoate (6S,E)-methyl 6-acetamido-7-oxo-7-(2-oxo-1-(2-oxo-2-(3-(trifluoromethyl)piperidin- 1-yl)ethyl)-1,2-dihydropyridin-3-ylamino)hept-2-enoate DFP-P04535WO10 Application (final).docx 161 (S,E)-methyl 7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(nicotinamido)-7-oxohept-2-enoate (6S,E)-methyl 6-(2-aminopropanamido)-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2- oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate 2,2,2-trifluoroacetate (S,E)-methyl 6-(2-aminoacetamido)-7-(3-((2-(2-ethylbutylamino)-2- oxoethyl)(methyl)amino)-3-oxoprop-1-en-2-ylamino)-7-oxohept-2-enoate 2,2,2- trifluoroacetate (S,E)-methyl 6-(2-aminobenzamido)-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo- 1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate 2,2,2-trifluoroacetate (S,E)-methyl 6-(3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthene]-5-ylcarboxamido)-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-methyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (2S,3R)-2-(2-(3-((S,E)-2-benzamido-7-methoxy-7-oxohept-5-enamido)-2- oxopyridin-1(2H)-yl)acetamido)-3-methylpentanoic acid (R,E)-methyl 7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (S,E)-2-acetamido-N-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- yl)-6-(methylsulfonyl)hex-5-enamide (S,E)-benzyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate (S,E)-methyl 6-acetamido-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxohept-2-enoate 2) Improved Michael Acceptors In some preferred embodiments the TG2 inhibitor is an irreversible TG2 inhibitor. In some further preferred embodiments, the irreversible TG2 inhibitor is a5 compound of the general formula (Iimp): DFP-P04535WO10 Application (final).docx 162 wherein L represents –L1– or –L1-L2–; and preferably –L1-L2–; L1represents –CH2–, –CH2CH2–, –CH2CH2CH2–, –CH2CO–, or –CH2CH2CO–; 5 L2represents a bond, –NRN1–, –NRN1CH2–, –NRN1CH2CH2–, or –NRN1CH(CH3)–; 10 , DFP-P04535WO10 Application (final).docx 163 DFP-P04535WO10 Application (final).docx 164 DFP-P04535WO10 Application (final).docx 165 ,, , , ,, , , , ,, , , , ,, , , , ,, , , , ,DFP-P04535WO10 Application (final).docx 166 wherein the unsubstituted bicyclic residues can be substituted with 1 to 5 of the substituents R9 –R14, RN; and preferably with 1 to 3 of the substituents R11 – R13;R3represents bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, 5 bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.2]nonyl, bicyclo[3.3.2]decyl, bicyclo[3.3.3]undecyl, 4-homoisotwistyl, adamantyl, diamantyl, hexamethylenetetraminyl and the afore-mentioned residues optionally contain one or more C=C double bond(s) and / or are substituted by one or more of Ra, Rb, Rc, Rd, and Re; 10 Ra, Rb, Rc, Rd, and Rerepresent independently of each other –H, –F, –Cl, –Br, –CN, –OH, –CH3, –CH2CH3, –CH2CH2CH3, –CH(CH3)2, –CHF2, –CF3, –CH2CF3, –COCH3, –COCH2CH3, –CO2H, –CO2CH3, –CO2C2H5, –CONH2, DFP-P04535WO10 Application (final).docx 167 –CONHCH3, –CON(CH3)2, –CONHC2H5, –CH2CO2H, –CH2CO2CH3, –CH2CO2C2H5, –CH2CONH2, –CH2CONHCH3, –CH2CON(CH3)2, –CH2CONHC2H5, –NHCOCH3, –NHCOC2H5, –NHCOCF3, –NHCOCH2CF3, –NHSO2CH3, –NHSO2C2H5, –NHSO2CHF2, –NHSO2CF3, or –NHSO2CH2CF3; 5 R4represents –R5, –OR5or –NR6R7; R5represents –H, –CH3, –CH2CH3, –CH2CH2CH3, –CH(CH3)2, –CH2CH2CH2CH3, –CH2CH(CH3)2, –C(CH3)3, –CH2CH2CH2CH2CH3, 10 –CH2CH=CH2, –CH2CH=CH(CH3), –CH2CH=C(CH3)2, –CH2CH=CHCH2CH3, –cyclo-C3H5, –cyclo-C4H7, –cyclo-C5H9, –cyclo-C6H11, –CH2–cyclo-C3H5, –CH2–cyclo-C4H7, –CH2–cyclo-C5H9, –CH2–cyclo-C6H11, –Ph, –CH2–Ph, –CH2OCH3, –CH2OCH2CH3, –CH2CH2OCH3, or –CH2CH2OCH2CH3; 15 R6and R7represent independently of each other –H, –CH3, –CH2CH3, 20 ;25 R8, R9, R10, R11, R12, R13, and R14represent independently of each other –H, –F, –Cl, –Br, –I, –OH, ^CN, –NO2, ^CH3, ^C2H5, ^C3H7, ^CH(CH3)2, ^C4H9, ^CH2^CH(CH3)2, ^CH(CH3)^C2H5,^C(CH3)3, ^cyclo-C3H5, ^CH2^cyclo^C3H5, ^CH2OH, ^CH2F, ^CHF2, ^CF3, ^CH2Cl, ^CH2Br, ^CH2I, ^CH2^CH2F, ^CH2^CHF2, ^CH2^CF3, ^CH2^CH2Cl, 30 ^CH2^CH2Br, ^CH2^CH2I, –OCH3, –OC2H5, –OC3H7, –OCH(CH3)2, –OC(CH3)3, –OC4H9, –OCHF2, –OCF3, −OCH2CF3, –OC2F5, −OCH2OCH3, –O-cyclo-C3H5, –OCH2-cyclo-C3H5, –O–C2H4-cyclo-C3H5, –CHO, –COCH3, –COCF3, –COC2H5, –COC3H7, –COCH(CH3)2, –COC(CH3)3, –COOH, –COOCH3, –COOC2H5, –COOC3H7, –COOCH(CH3)2, –COOC(CH3)3, 35 –OOC–CH3, –OOC–CF3, –OOC–C2H5, –OOC–C3H7, –OOC–CH(CH3)2, –OOC–C(CH3)3, –NH2, –NHCH3, –NHC2H5, –NHC3H7, –NHCH(CH3)2, –NHC(CH3)3, –N(CH3)2, –N(C2H5)2, –N(C3H7)2, –N[CH(CH3)2]2, –N[C(CH3)3]2, DFP-P04535WO10 Application (final).docx 168 –NHCOCH3, –NHCOCF3, –NHCOC2H5, –NHCOC3H7, –NHCOCH(CH3)2, –NHCOC(CH3)3, –CONH2, –CONHCH3, –CONHC2H5, –CONHC3H7, –CONHCH(CH3)2, –CONH^cyclo-C3H5, –CONHC(CH3)3, –CON(CH3)2, –CON(C2H5)2, –CON(C3H7)2, –CON[CH(CH3)2]2, –CON[C(CH3)3]2, –SO2NH2, 5 –SO2NHCH3, –SO2NHC2H5, –SO2NHC3H7, –SO2NHCH(CH3)2, –SO2NH^cyclo-C3H5, –SO2NHC(CH3)3, –SO2N(CH3)2, –SO2N(C2H5)2, 10 15 20 25 30 DFP-P04535WO10 Application (final).docx 169 –SO2CH3, –SO2CF3, –SO2C2H5, –SO2C3H7, –SO2CH(CH3)2, –SO2^cyclo^C3H5, or –SO2C(CH3)3; RN1represents –H, –CH3, or –CH2CH3; 5 or a diastereomer, an enantiomer, a mixture of diastereomers, a mixture of enantiomers, a racemate, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof. 10 In some further preferred embodiments, the irreversible TG2 inhibitor is a compound of the general formula (Iimp), wherein wherein L represents –L1– or –L1–L2–; and preferably –L1-L2–; 15 L1represents –CH2–, –CH2CH2–, –CH2CH2CH2–, –CH2CO–, or –CH2CH2CO–; L2represents a bond, –NRN1–, –NRN1CH2–, –NRN1CH2CH2–, or –NRN1CH(CH3)–; R1 represents ; R2represents 20 DFP-P04535WO10 Application (final).docx 170 5 DFP-P04535WO10 Application (final).docx 171 DFP-P04535WO10 Application (final).docx 172 DFP-P04535WO10 Application (final).docx 173 R3represents bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.2]nonyl, bicyclo[3.3.2]decyl, bicyclo[3.3.3]undecyl, 4-homoisotwistyl, adamantyl, diamantyl, or hexamethylenetetraminyl and the afore-mentioned residues optionally contain 5 one or more C=C double bond(s) and / or are optionally substituted by one or more of Ra, Rb, Rc, Rd, and Re; Ra, Rb, Rc, Rd, and Rerepresent independently of each other –H, –F, –Cl, –Br, –CN, –OH, –CH3, –CH2CH3, –CH2CH2CH3, –CH(CH3)2, –CHF2, –CF3, 10 –CH2CF3, –COCH3, –COCH2CH3, –CO2H, –CO2CH3, –CO2C2H5, –CONH2, –CONHCH3, –CON(CH3)2, –CONHC2H5, –CH2CO2H, –CH2CO2CH3, –CH2CO2C2H5, –CH2CONH2, –CH2CONHCH3, –CH2CON(CH3)2, –CH2CONHC2H5, –NHCOCH3, –NHCOC2H5, –NHCOCF3, –NHCOCH2CF3, –NHSO2CH3, –NHSO2C2H5, –NHSO2CHF2, –NHSO2CF3, or –NHSO2CH2CF3; 15 R4represents –R5, –OR5or –NR6R7; DFP-P04535WO10 Application (final).docx 174 R5represents –H, –CH3, –CH2CH3, –CH2CH2CH3, –CH(CH3)2, –CH2CH2CH2CH3, –CH2CH(CH3)2, –C(CH3)3, –CH2CH2CH2CH2CH3, –CH2CH=CH2, –CH2CH=CH(CH3), –CH2CH=C(CH3)2, –CH2CH=CHCH2CH3, –cyclo-C3H5, –cyclo-C4H7, –cyclo-C5H9, –cyclo-C6H11, –CH2–cyclo-C3H5, 5 –CH2–cyclo-C4H7, –CH2–cyclo-C5H9, –CH2–cyclo-C6H11, –CH2–Ph, –CH2OCH3, –CH2OCH2CH3, –CH2CH2OCH3, or –CH2CH2OCH2CH3; R6and R7represent independently of each other –H, –CH3, –CH2CH3, 10 15 , , ;R8, R9, R10, R11, R12, R13, and R14represent independently of each other –H, –F, –Cl, –Br, –I, –OH, ^CN, –NO2, ^CH3, ^C2H5, ^C3H7, ^CH(CH3)2, ^C4H9, ^CH2^CH(CH3)2, ^CH(CH3)^C2H5,^C(CH3)3, 20 ^cyclo-C3H5, ^CH2^cyclo^C3H5, ^CH2F, ^CHF2, ^CF3, ^CH2Cl, ^CH2Br, ^CH2I, ^CH2^CH2F, ^CH2^CHF2, ^CH2^CF3, ^CH2^CH2Cl, ^CH2^CH2Br, ^CH2^CH2I, –OCH3, –OC2H5, –OC3H7, –OCH(CH3)2, –OC(CH3)3, –OC4H9, –OCHF2, –OCF3, −OCH2CF3, –OC2F5, −OCH2OCH3, –O-cyclo-C3H5, –OCH2-cyclo-C3H5, –O–C2H4-cyclo-C3H5, –CHO, 25 –COCH3, –COCF3, –COC2H5, –COC3H7, –COCH(CH3)2, –COC(CH3)3, –COOH, –COOCH3, –COOC2H5, –COOC3H7, –COOCH(CH3)2, –COOC(CH3)3, –OOC–CH3, –OOC–CF3, –OOC–C2H5, –OOC–C3H7, –OOC–CH(CH3)2, –OOC–C(CH3)3, –NH2, –NHCH3, –NHC2H5, –NHC3H7, –NHCH(CH3)2, –NHC(CH3)3, –N(CH3)2, –N(C2H5)2, –N(C3H7)2, –N[CH(CH3)2]2, –N[C(CH3)3]2, 30 –NHCOCH3, –NHCOCF3, –NHCOC2H5, –NHCOC3H7, –NHCOCH(CH3)2, –NHCOC(CH3)3, –CONH2, –CONHCH3, –CONHC2H5, –CONHC3H7, –CONHCH(CH3)2, –CONH^cyclo-C3H5, –CONHC(CH3)3, –CON(CH3)2, –CON(C2H5)2, –CON(C3H7)2, –CON[CH(CH3)2]2, –CON[C(CH3)3]2, –SO2NH2, –SO2NHCH3, –SO2NHC2H5, –SO2NHC3H7, –SO2NHCH(CH3)2, 35 –SO2NH^cyclo-C3H5, –SO2NHC(CH3)3, –SO2N(CH3)2, –SO2N(C2H5)2, –SO2N(C3H7)2, –SO2N[CH(CH3)2]2, –SO2N[C(CH3)3]2, –NHSO2CH3, –NHSO2CF3, –NHSO2C2H5, –NHSO2C3H7, –NHSO2CH(CH3)2, DFP-P04535WO10 Application (final).docx 175 5 or R8and R9or R9and R10can form together one of the following five- membered or six-membered rings: 10 15 20 RN1represents –H, –CH3, or –CH2CH3; 25 or a diastereomer, an enantiomer, a mixture of diastereomers, a mixture of enantiomer, a racemate, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof. DFP-P04535WO10 Application (final).docx 176 In some further preferred embodiments, the irreversible TG2 inhibitor is a compound of the general formula (Iimp), wherein 5 10 DFP-P04535WO10 Application (final).docx 177 5 wherein the unsubstituted bicyclic residues can be substituted with 1 to 5 of the substituents R9–R14, and RN; and preferably with 1 to 3 of the substituents R11 – R13, and R5 – R14 and RN have the meanings as defined herein forcompound of the general formula (Iimp). 10 In some further preferred embodiments, the irreversible TG2 inhibitor is a compound of the general formula (Iimp), wherein R2represents 15 , DFP-P04535WO10 Application (final).docx 178 DFP-P04535WO10 Application (final).docx 179 DFP-P04535WO10 Application (final).docx 180 ,DFP-P04535WO10 Application (final).docx 181 wherein the unsubstituted bicyclic residues can be substituted with 1 to 5 of the substituents R9 – R14, RN; and preferably with 1 to 3 of the substituents R11 – R13and the substituents R9–R14, and RNhave the meanings as defined herein for a compound of the general formula (Iimp). 5 In some further preferred embodiments, the irreversible TG2 inhibitor is a compound of the general formula (Iimp), wherein DFP-P04535WO10 Application (final).docx 182 L1represents –CH2–, or –CH2CO–; L2represents a bond, –NRN1–, –NRN1CH2–, or –NRN1CH(CH3)–; R3represents bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, 4-homoisotwistyl, 5 adamantyl, or diamantyl and the afore-mentioned residues optionally contain one or more C=C double bond(s) and / or are substituted by one or more of Ra, Rb, Rc, Rd, and Re; and R5, R6, R7, Ra, Rb, Rc, Rd, Reand RN1have the same meanings as defined herein for a compound of the general formula (Iimp). 10 In some further preferred embodiments, the irreversible TG2 inhibitor is a compound of the general formula (Iimp), wherein the compound has any one of the formulae (VI-aimp) – (Vl-limp), (VII-aimp) – (VII-limp), (VIII-aimp) – (VIIl-limp), (IX-aimp)– (IX-dimp), (X-aimp) – (X-dimp), and (XI-aimp) – (XI-dimp):15 DFP-P04535WO10 Application (final).docx 183 DFP-P04535WO10 Application (final).docx 184 (VIII-aimp) (VIII-bimp) DFP-P04535WO10 Application (final).docx 185 (VIII-gimp) (VIII-himp)(( DFP-P04535WO10 Application (final).docx 186 DFP-P04535WO10 Application (final).docx 187 and R2, R3, R5, R6, R7, R8, R9, R10, R11, R12, R13, Ra, Rb, Rc, Rd and L2 have thesame meanings as defined herein for a compound of the general formula (Iimp).In some further preferred embodiments, the irreversible TG2 inhibitor is a 5 compound of the general formula (Iimp), wherein 10 15 , DFP-P04535WO10 Application (final).docx 188 5 10 In some further preferred embodiments, the irreversible TG2 inhibitor is a compound of the general formula (Iimp), wherein 15 R3represents DFP-P04535WO10 Application (final).docx 189 5 In some further preferred embodiments, the irreversible TG2 inhibitor selected10 from the group consisting of: DFP-P04535WO10 Application (final).docx 190 DFP-P04535WO10 Application (final).docx 191 DFP-P04535WO10 Application (final).docx 192 DFP-P04535WO10 Application (final).docx 193 DFP-P04535WO10 Application (final).docx 194 DFP-P04535WO10 Application (final).docx 195 DFP-P04535WO10 Application (final).docx 196 (6S,E)-methyl 7-(1-(2-((1R,2R,4S)-bicyclo[2.2.1]heptan-2-ylamino)-2- III-98: oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-6-(4-methyl-2- (trifluoromethyl)thiazole-5-carboxamido)-7-oxohept-2-enoate (S,E)-ethyl 7-(1-(2-(2-adamantylamino)-2-oxoethyl)-2-oxo-1,2- III-99: dihydropyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7- oxohept-2-enoate (S,E)-N-(1-(1-(2-(2-adamantylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3- III- ylamino)-6-(methylsulfonyl)-1-oxohex-5-en-2-yl)-1-methyl-1H-imidazole-5- 100: carboxamide III- (S,E)-methyl 7-(1-(2-(2-adamantylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxo-6-(2H-1,2,3-triazole-4-carboxamido)hept-2- 101: enoate III- (S,E)-methyl 7-(1-(2-(2-adamantylamino)-2-oxoethyl)-2-oxo-1,2- dihydropyridin-3-ylamino)-7-oxo-6-(1H-1,2,3-triazole-4-carboxamido)hept-2- 102: enoate DFP-P04535WO10 Application (final).docx 197 DFP-P04535WO10 Application (final).docx 198 DFP-P04535WO10 Application (final).docx 199 DFP-P04535WO10 Application (final).docx 200 DFP-P04535WO10 Application (final).docx 201 DFP-P04535WO10 Application (final).docx 202 or a pharmaceutically acceptable salt thereof. Particularly preferred TG2 Inhibitors A herein particularly preferred TG2 inhibitor is (S,E)-methyl-7-(1-(2-(2-5 ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H- imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1): DFP-P04535WO10 Application (final).docx 203 Compound 1 Pharmaceutical Composition & Medical Use 5The compounds of general formula (Irev), (Iirr), and (Iimp) as described herein,preferably Compound 1, may be administered themselves or in form of apharmacologically acceptable salt. The compounds of general formula (Irev), (Iirr), and (Iimp) as described herein, 10 preferably Compound 1, may form of a pharmacologically acceptable salt with organic or inorganic acids or bases. Examples of suitable acids for such acid addition salt formation are hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, oxalic acid, malonic acid, salicylic acid, p- aminosalicylic acid, malic acid, fumaric acid, succinic acid, ascorbic acid, maleic 15 acid, sulfonic acid, phosphonic acid, perchloric acid, nitric acid, formic acid, propionic acid, gluconic acid, lactic acid, tartaric acid, hydroxymaleic acid, pyruvic acid, phenylacetic acid, benzoic acid, p-aminobenzoic acid, p-hydroxybenzoic acid, methanesulfonic acid, ethanesulfonic acid, nitrous acid, hydroxyethanesulfonic acid, ethylenesulfonic acid, p-toluenesulfonic acid, 20 naphthylsulfonic acid, sulfanilic acid, camphorsulfonic acid, china acid, mandelic acid, o-methylmandelic acid, hydrogen-benzenesulfonic acid, picric acid, adipic acid, d-o-tolyltartaric acid, tartronic acid, (o, m, p)-toluic acid, naphthylamine sulfonic acid, trifluoroacetic acid, and other mineral or carboxylic acids well known to those skilled in the art. The salts are prepared by contacting the free base form 25 with a sufficient amount of the desired acid to produce a salt in the conventional manner. Preferred is the mesylate salt, hydrochloride salt and the trifluoroacetate salt and especially preferred is the trifluoroacetate salt and the hydrochloride salt. In the case the compounds of general formula (Irev), (Iirr), and (Iimp) as described 30 herein, preferably Compound 1, bear acidic groups, salts could also be formed with inorganic or organic bases. Examples for suitable inorganic or organic bases are, for example, NaOH, KOH, NH4OH, tetraalkylammonium hydroxide, lysine or arginine and the like. Salts may be prepared in a conventional manner using DFP-P04535WO10 Application (final).docx 204 methods well known in the art, for example by treatment of a solution of the compounds of general formula (Irev), (Iirr), and (Iimp) as described herein, preferably Compound 1, with a solution of an acid, selected out of the group mentioned above. 5 Furthermore, the compounds of general formula (Irev), (Iirr), and (Iimp) as describedherein, preferably Compound 1, as described herein may be administered in form of a pharmaceutical composition comprising at least one of the compounds ofgeneral formula (Irev), (Iirr), and (Iimp) as described herein, preferably Compound10 1, as described herein as an active ingredient or a pharmacologically acceptablesalts thereof as an active ingredient, together with at least one pharmacologically acceptable carrier, excipient and / or diluent. Furthermore, the compounds of general formula (Irev), (Iirr), and (Iimp) as described 15 herein, preferably Compound 1, as described herein can be administered in form of their pharmaceutically active salts, optionally using essentially non-toxic pharmaceutically acceptable carriers, adjuvants or extenders. Medications are prepared in a known manner in a conventional solid or fluid carrier or in extenders and a conventional pharmaceutically acceptable adjuvant / expedient in a suitable 20 dose. The preferred preparations are provided in an administrable form suitable for oral application, such as pills, tablets, film tablets, coated tablets, capsules and powders. Tablets, film tablets, coated tablets, gelatin capsules and opaque capsules are the 25 preferred pharmaceutical formulations. Any pharmaceutical compositions contains at least one compound of the general formula (I), and / or pharmaceutically acceptable salts thereof in an amount of 5 mg to 500 mg, preferably 10 mg to 250 mg and most preferred in an amount of 10 to 100 mg per formulation. 30 Besides, the object of the present invention also includes pharmaceutical preparations for oral, parenteral, dermal, intradermal, intragastric, intracutaneous, intravascular, intravenous, intramuscular, intraperitoneal, intranasal, intravaginal, intrabuccal, percutaneous, rectal, subcutaneous, sublingual, topic, transdermal or inhalative application, containing, in addition to typical vehicles and extenders, a 35 compound of the general formula (I), and / or a pharmaceutically acceptable salt thereof as active component. The pharmaceutical compositions of the present invention contain one of the compounds of general formula (Irev), (Iirr), and (Iimp) as described herein, preferably DFP-P04535WO10 Application (final).docx 205 Compound 1, disclosed herein as active component, typically mixed with suitable carrier materials, selected with respect to the intended form of administration, i.e. tablets to be administered orally, capsules (filled either with a solid, a semi-solid or a liquid), powders, orally administrable gels, elixirs, dispersible granulates, syrups, 5 suspensions and the like in accordance with conventional pharmaceutical practices. For example, the compound of the formula (I) can as active agent component be combined with any oral, non-toxic, pharmaceutically acceptable, inert carrier, such as lactose, starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, talc, mannitol, ethyl alcohol (liquid forms) 10 and the like for the oral administration in form of tablets or capsules. Moreover, suitable binders, lubricants, disintegrants and colorants can be added to the mixture if required. Powders and tablets can consist of said inert carriers to an extent from about 5% per weight to about 95% per weight of the pharmaceutical composition. 15 Suitable binders include starch, gelatin, natural sugars, sweeteners made of corn, natural and synthetic gums, such as acacia gum, sodium alginate, carboxymethylcellulose, polyethylene glycol and waxes. Possible lubricants for the use in said dosage forms include boric acid, sodium benzoate, sodium acetate, 20 sodium chloride and the like. Disintegrants include starch, methylcellulose, cyclodextrins, guar gum and the like. If required, sweeteners and flavor additives and preservatives can also be included. Some of the terms used above, namely disintegrants, extenders, lubricants, binders and the like are discussed in greater detail below. 25 Additionally, the compositions of the present invention can be formulated in a form with sustained release to provide a controlled release rate of any one or more components or active components, in order to optimize the therapeutic effect, i.e. the inhibitory activity and the like. Suitable dosage forms for sustained release 30 include layered tablets containing layers with varying degradation rates or controlled release polymeric matrices impregnated with the active components and in the form of a tablet or capsule containing such impregnated or encapsulated porous polymeric matrices. 35 Preparations in fluid form include solutions, suspensions and emulsions. Exemplarily mentioned are water or water propylene glycol solutions for parenteral injections or the addition of sweeteners and opacifiers for oral solutions, suspensions and emulsions. DFP-P04535WO10 Application (final).docx 206 Aerosol preparations suitable for inhalation may include solutions and solids in the form of powders which can be combined with a pharmaceutically acceptable carrier, such as a compressed inert gas, e.g. nitrogen. 5 For the preparation of suppositories a low melting wax, such as a mixture of fatty acid glycerides, e.g. cocoa butter, is melted firstly and the active component is homogenously dispersed therein by stirring or similar mixing operations. The melted homogenous mixture is then poured in fitting forms, cooled and thus hardened. 10 Further preparations in solid form which are to be converted into preparations in fluid form for either oral or parenteral administration shortly before use are included. Such fluid forms include solutions, suspensions and emulsions. 15 Furthermore, the compounds of the present invention may be administered via transdermal application. The transdermal compositions can have the form of crèmes, lotions, aerosols and / or emulsions. The term capsule refers to a special container or casing composed of 20 methylcellulose, polyvinyl alcohols or denatured gelatins or starches, in which the active agents can be enclosed. Typically, hard shell capsules are prepared from mixtures of bones and porcine skin gelatins having comparatively high gel strength. The capsule itself can contain small amounts of colorants, opacifiers, softening agents and preservatives. 25 Tablet means a compressed or cast solid dosage form containing the active components with suitable extenders. The tablet can be produced by compressing mixtures or granulates obtained by wet granulation, dry granulation or compaction, which are known to the one skilled in the art. 30 Oral gels refer to the active components dispersed or solubilized in a hydrophilic semi-solid matrix. Powders for compositions refer to powder mixtures containing the active35 components and suitable extenders which can be suspended in water or juices. Suitable extenders are substances which usually form the largest part of the composition or dosage form. Suitable extenders include sugars such as lactose, sucrose, mannitol and sorbitol; starches derived from wheat, corn, rice and DFP-P04535WO10 Application (final).docx 207 potatoes; and celluloses such as microcrystalline cellulose. The amount of extenders in the composition can range from about 5 to about 95% per weight of the total composition, preferably form about 25 to about 75% per weight and further preferred from about 30 to about 60% per weight. 5 The term disintegrants refers to materials added to the composition in order to support disintegration and release of the medicinal substance. Suitable disintegrants include starches, modified starches which are soluble in cold water, such as sodium carboxymethyl starch; natural and synthetic gums such as locust 10 bean gum, caraya, guar gum, tragacanth and agar; cellulose derivatives such as methylcellulose and sodium carboxymethylcellulose, microcrystalline celluloses and crosslinked microcrystalline celluloses such as croscarmellose sodium; alginates such as alginic acid and sodium alginate; clays such as bentonites and foaming mixtures. The amount of disintegrants used in the composition can range 15 from about 2 to 20% per weight of the composition and further preferred from about 5 to about 10% per weight. Binders characterize substances binding or "gluing" powders to each other and they consequently serve as "glue" in the formulation. Binders add a cohesion 20 starch which is already available in the extenders or the disintegrant. Suitable binders include sugar, such as sucrose; starches derived from wheat, corn, rice and potatoes; natural gums such as acacia gum, gelatin and tragacanth; derivatives of sea weed such as alginic acid, sodium alginate and ammonium calcium alginate, cellulose materials such as methyl cellulose and sodium 25 carboxymethylcellulose and hydroxypropyl methylcellulose, polyvinylpyrrolidone and inorganic compounds, such as magnesium aluminum silicate. The amount of binders in the composition can range from about 2 to about 20% per weight of the total composition, preferably form about 3 to about 10% per weight and further preferred from about 3 to about 6% per weight. 30 The term lubricant refers to a substance added to the dosage form in order to allow for the tablet, granulate, etc. to be released from the casting mold or pressing mold, after compression, by reducing the friction. Suitable lubricants include metallic stearates such as magnesium stearate, calcium stearate or 35 potassium stearate; stearic acid; waxes with high melting points and water soluble lubricants such as sodium chloride, sodium benzoate, sodium acetate, sodium oleate, polyethylene glycols and D,L-leucine. Due to the fact that lubricants have to be present on the surface of the granulates as well as between the granulates DFP-P04535WO10 Application (final).docx 208 and parts of the tablet press they are typically added during the last step prior to compression. The amount of lubricants in the composition can range from about 0.2 to about 5% per weight of the total composition, preferably form about 0.5 to about 2% per weight and further preferred from about 0.3 to about 1.5 % per5 weight. Lubricants are materials preventing caking and improving the flow characteristics of granulates so that the flow is smooth and uniform. Suitable lubricants include silicon dioxide and talc. The amount of lubricants in the composition can range10 from about 0.1 to about 5 % per weight of the total composition, preferably formabout 0.5 to about 2 % per weight.Colorants are adjuvants coloring the composition or dosage form. Such adjuvants can include colorants having food quality which are adsorbed on a suitable 15 adsorption means, such as clay or aluminum oxide. The amount of the colorant used can vary from about 0.1 to about 5% per weight of the composition and preferably from about 0.1 to about 1% per weight. The term “systemic formulation” refers to a pharmaceutical composition suitable 20 for administration such that a drug or active agent is administered systemically throughout the body of an organism, e.g. a form of medication for the circulatory system so that the entire body is affected. Administration can take place via enteral administration (abso...

Claims

250 Claims 1. A computer-implemented method for selecting a therapy regimen for a5 subject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at least one transglutaminase 2 inhibitor in the treatment of celiac disease of said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,10 wherein the human leukocyte antigen class II genotype comprisehuman leukocyte antigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined humanleukocyte antigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,15 (ii) a second gluten-sensitive DQ genotype group, or(iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten-specific T-cell response than the second gluten-sensitive DQ genotype group, wherein the second gluten-sensitive DQ genotype 20 group has a stronger gluten-specific T cell response than the third gluten-sensitive DQ genotype group, wherein stronger gluten-specific T-cell response is characterized by a more dysregulated genexpression of genes related to mature enterocytes and / or cell proliferation and / or inflammation; and25 (c) selecting or adjusting a therapy regimen for said subject based on theDQ genotype group (i), (ii), or (iii) of said subject , wherein the therapy regimen comprises one or more therapeutic measures selected from a dose level of transglutaminase 2 inhibitor, an administration interval of transglutaminase 2 inhibitor, type of transglutaminase 2 inhibitor, 30 and duration of treatment, wherein one or more of the therapeutic measures vary depending on whether said subject applying to DQ genotype group (i), (ii), or (iii), and wherein selecting or adjusting a therapy regimen for said subject comprises selecting or adjusting one or more of the therapeutic measures based on the DQ genotype group of said subject35 wherein the human leukocyte antigen DQ haplotypes include one or moreof HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA- DQ8, and HLA-DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, and preferably DFP-P04535WO10 Application (final).docx251 wherein the HLA-DQ2 haplotypes are selected from the group comprising or consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA- DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising or consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of 10 DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO.

2. The computer-implemented method according to claim 1, wherein before15 step (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;(a’’) determining the human leukocyte antigen class II genotype of saidsubject in said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one 20 or more of human leukocyte antigen DQ alleles and haplotypes of said subject.

3. The computer-implemented method according to claim 1 or 2, wherein for asubject applying to the first gluten-sensitive DQ genotype group (i) the 25 therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering a more potent TG2 inhibitor thana therapeutic regimen for a subject applying to the second gluten-sensitive DQ genotype group (ii) or third gluten-sensitive DQ genotype group (iii). 30 4. The method according to any one of the claims 1 – 3, wherein the humanleukocyte antigen DQ haplotypes include at least HLA-DQ2 and HLA-DQ8 haplotypes, and wherein the HLA-DQ2 haplotypes are selected from the group comprising or 35 consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA- DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 DFP-P04535WO10 Application (final).docx252 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and wherein the HLA-DQ8 haplotypes are selected from the group comprising or consisting of: 5 HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO.10 5. The computer-implemented method according to any one of the claims 1 – 4,wherein step (b) further comprises: identifying said subject as applying to first gluten-sensitive DQ genotype group (i) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02, or 15 identifying said subject as applying to second gluten-sensitive DQ genotype group (ii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2.2 HOMO, DQ8 HOMO, DQ8 / DQ2, DQ2.5 / DQ2.2, or identifying said subject as applying to third gluten-sensitive DQ genotype group (iii) if the HLA-DQ2 and HLA-DQ8 haplotypes are DQ2 half 20 heterodimer, DQ2.2 HETERO, DQ2.5 HETERO, DQ2.5 TrHETERO, DQ8 HETERO, DQ2.5 / one copy of DQA1*05.

6. The computer-implemented method according to any one of the claims 1 – 5,wherein a subject applying to the first gluten-sensitive DQ genotype group is25 characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0, preferably between -1.0 to -2.7 from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet.

7. The computer-implemented method according to any one of the claims 1 – 6,30 wherein a subject applying to the second gluten-sensitive DQ genotype group is characterized by a change in villous height to crypt depth (VH:CrD)ratio between -0.1 to -1.3, between -0.4 to -1.0 from a villous height to cryptdepth (VH:CrD) ratio of a comparative subject on gluten-free diet.35 8. The computer-implemented method according to any one of the claims 1 – 7,wherein a subject applying to the third gluten-sensitive DQ genotype group ischaracterized by a change in villous height to crypt depth (VH:CrD) ratio DFP-P04535WO10 Application (final).docx253 between -0.05 to -0.7, preferably between -0.1 to -0.4 from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet.

9. The computer-implemented method according to any one of the claims 1 – 8,5 wherein step b) comprises: (b) identifying said subject, at least based on the determined humanleukocyte antigen DQ haplotypes of said subject, as applying to (i) a first gluten-sensitive DQ genotype group,(ii) a second gluten-sensitive DQ genotype group, or10 (iii) a third gluten-sensitive DQ genotype group,wherein the first gluten-sensitive DQ genotype group has a stronger gluten-specific T-cell response than the second gluten-sensitive DQ genotype group characterized by a change in villous height to crypt depth (VH:CrD) ratio between -0.7 to -3.0, preferably between -1.0 to 15 -2.7 from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet; wherein the second gluten-sensitive DQ genotype group has a stronger gluten-specific T cell response than the third gluten-sensitive DQ genotype group characterized by a change in villous height to crypt20 depth (VH:CrD) ratio between -0.1 to -1.3, between -0.4 to -1.0 from avillous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet; wherein third gluten-sensitive DQ genotype group has a gluten-specific T cell response characterized by a change in villous height to crypt 25 depth (VH:CrD) ratio between -0.05 to -0.7, preferably between -0.1 to -0.4 from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet wherein stronger gluten-specific T-cell response is characterized by amore dysregulated genexpression of genes related to mature30 enterocytes and / or cell proliferation and / or inflammation.

10. The computer-implemented method according to any one of the claims1 – 9, wherein the first gluten-sensitive DQ genotype group has a moredysregulated genexpression than the third gluten-sensitive DQ genotype 35 group, wherein more dysregulated genexpression is characterized byat least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 are at least 50% more downregulated in the first gluten-DFP-P04535WO10 Application (final).docx254 sensitive DQ genotype group than in the third gluten-sensitive DQ genotypegroup, preferably between 50% – 90%; and / orat least one, preferably more than one of the genes AGR2, MKI167,and CENPF are at least 30% more upregulated in the first gluten-sensitive5 DQ genotype group than in the third gluten-sensitive DQ genotype group,preferably between 33 -100%; and / or at least one, preferably more than one of the genes STAT1, GBP1 and TGM2 are at least 50% more upregulated in the first gluten-sensitiveDQ genotype group than in the third gluten-sensitive DQ genotype group,10 preferably between 50% – 100%.

11. The computer-implemented method according to any one of the claims1 – 10, wherein the second gluten-sensitive DQ genotype group has a moredysregulated genexpression than the third gluten-sensitive DQ genotype 15 group, wherein more dysregulated genexpression is characterized by at least one, preferably more than one of the genes APOB, APOA1, and TM4SF4 are are between 10% – 49% more downregulated in thesecond gluten-sensitive DQ genotype group than in the third gluten-20 sensitive DQ genotype group; and / or at least one, preferably more than one of the genes AGR2, MKI167,and CENPF are between 10% – 29% more upregulated in the secondgluten-sensitive DQ genotype group than in the third gluten-sensitive DQgenotype group, preferably between 12% – 25%; and / or25 at least one, preferably more than one of the genes STAT1, GBP1 and TGM2 are between 1% – 49% more upregulated in the second gluten-sensitive DQ genotype group than in the third gluten-sensitive DQ genotypegroup, preferably between 5% – 20%.30 12. The computer-implemented method according to any one of the claims1 – 11, wherein the first gluten-sensitive DQ genotype group has a moredysregulated group of genes of a biological pathway than the third gluten-sensitive DQ genotype group, wherein a more dysregulated group of genes of a biological pathway is35 characterized by for transit amplifying cells, genes from the first gluten-sensitive DQ genotype group are on average at least 50% more upregulated than genesfrom the third gluten-sensitive DQ genotype group, and / or DFP-P04535WO10 Application (final).docx255 for mature enterocytes genes from the first gluten-sensitive DQgenotype group are on average at least 200% more downregulated than genes from the third gluten-sensitive DQ genotype group, and / or for immune cells, genes from the first gluten-sensitive DQ genotype5 group are on average at least 100% more upregulated than genes from thethird gluten-sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the first gluten-sensitiveDQ genotype group are on average at least 200% more upregulated thangenes from the third gluten-sensitive DQ genotype group. 10 13. The computer-implemented method according to any one of the claims1 – 12, wherein the second gluten-sensitive DQ genotype group has a moredysregulated group of genes of a biological pathway than the third gluten-sensitive DQ genotype group,15 wherein a more dysregulated group of genes of a biological pathway ischaracterized by for transit amplifying cells, genes from the second gluten-sensitive DQ genotype group are on average at least 20% more upregulated than genes from the third gluten-sensitive DQ genotype group, and / or20 for mature enterocytes, genes from the second gluten-sensitive DQgenotype group are on average at least 50% more downregulated thangenes from the third gluten-sensitive DQ genotype group, and / orfor immune cells, genes from the second gluten-sensitive DQgenotype group are on average at least 5% more upregulated than genes25 from the third gluten-sensitive DQ genotype group, and / or for duodenal transporter cells, genes from the second gluten-sensitive DQ genotype group are on average at least 50% more upregulated than genes from the third gluten-sensitive DQ genotype group.30 14. The computer-implemented method according to any one of the claims1 – 13, wherein the therapy regimen comprises TG2 inhibitor at a daily dosebetween 0.1 mg – 1000 mg, preferably between 0.5 mg – 500 mg, morepreferably between 25 mg – 250 mg, most preferably between 1 mg – 100mg. 35 15. The computer-implemented method according to any one of the claims1 – 14, wherein the therapy regimen comprises TG2 inhibitor at a daily dosebetween 150 mg – 250 mg, more preferably between 160 mg – 240 mg,DFP-P04535WO10 Application (final).docx256 more preferably between 170 mg – 230 mg, more preferably between 180mg – 220 mg, more preferably between 190 mg – 210 mg, preferably for thefirst gluten-sensitive DQ genotype.

516. The computer-implemented method according to any one of the claims1 – 15, wherein the therapy regimen for the first gluten-sensitive DQgenotype group comprises TG2 inhibitor at a daily dose between 25 mg – 1000 mg, preferably between 25 mg – 500 mg, more preferably between 25mg – 250 mg, most preferably between 30 mg – 100 mg, and / or10 wherein the therapy regimen for the second gluten-sensitive DQ genotype group comprises TG2 inhibitor at a daily dose between 5 mg – 750 mg,more preferably between 5 mg – 250 mg, preferably between 5 mg – 75mg, most preferably between 10 mg – 30 mg, and / orwherein the therapy regimen for the third gluten-sensitive DQ genotype15 group comprises TG2 inhibitor at a daily dose between 0.1 mg – 500 mg,more preferably between 0.1 mg – 250 mg, preferably between 0.1 mg – 50mg, most preferably between 1 mg – 10 mg.

17. The computer-implemented method according to any one of the claims20 1 – 16, wherein the therapy regimen for the first gluten-sensitive DQgenotype group comprises TG2 inhibitor at a daily dose between 150 mg –250 mg, more preferably between 160 mg – 240 mg, more preferablybetween 170 mg – 230 mg, more preferably between 180 mg – 220 mg,more preferably between 190 mg – 210 mg most preferably at a daily dose25 of (about) 200 mg.

18. The computer-implemented method according to any one of the claims1 – 17, wherein step b) further comprisesidentifying said subject, at least based on the determined human leukocyte 30 antigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or as a subject suffering from refractory coeliac disease; and applying said subject to the first gluten-sensitive DQ genotypegroup.35 19. A computer-implemented method for selecting a therapy regimen for asubject having been diagnosed with celiac disease, wherein the therapy regimen comprises at least the use of a therapeutically effective amount of at DFP-P04535WO10 Application (final).docx257 least one transglutaminase 2 inhibitor in the treatment of the celiac disease of said subject, the method comprising: (a) providing a human leukocyte antigen class II genotype of said subject,wherein the human leukocyte antigen class II genotype comprise5 human leukocyte antigen DQ haplotypes of said subject; (b) identifying said subject, at least based on the determined humanleukocyte antigen DQ haplotypes of said subject, as a subject having a risk for refractory coeliac disease or as a subject suffering from refractory coeliac disease;10 (c) selecting or adjusting a therapy regimen for said subject if the subjecthas been identified having a risk for refractory coeliac diseases or suffering from refractory coeliac diseases , wherein the therapy regimen comprises one or more therapeutic measures selected from dose level of TG2 inhibitor, administration interval of TG215 inhibitor, type of TG2 inhibitor, and duration of treatment.

20. The computer-implemented method according to claim 19, wherein beforestep (a) the method further comprises steps (a’) and (a’’): (a’) obtaining an ex-vivo sample of genetic material from said subject;20 (a’’) determining the human leukocyte antigen class II genotype of saidsubject in said ex-vivo sample of genetic material, wherein the human leukocyte antigen class II genotype comprises one or more of human leukocyte antigen DQ alleles and haplotypes of said subject.25 21. The computer-implemented method according to Claims 19 or 20, whereinthe human leukocyte antigen DQ haplotypes include one or more of HLA-DQ2, HLA-DQ3, HLA-DQ4, HLA-DQ5, HLA-DQ6, HLA-DQ7, HLA-DQ8, and HLA-DQ9 haplotypes, preferably HLA-DQ2 and HLA-DQ8 haplotypes, and preferably, 30 wherein the HLA-DQ2 haplotypes are selected from the group consisting of: HLA-DQ2.2 / HLA-DQ2.2, HLA-DQ2.3 / HLA-DQ2.3, HLA-DQ2.5 / HLA- DQ2.5; HLA-DQ2.2 homodimer, HLA-DQ2.3 homodimer, HLA-DQ2.5 homodimer; HLA-DQ2.2 heterodimer, HLA-DQ2.3 heterodimer, HLA-DQ2.5 heterodimer; and 35 wherein the HLA-DQ8 haplotypes are selected from the group consisting of: HLA-DQ8 homodimer, HLA-DQ8 heterodimer, DQ2.5 / one copy of DQB1*02, DQ2.5 / DQ2.3, DQ2.5 / DQ2.2, DQ8 / DQ2, DQ2 half DFP-P04535WO10 Application (final).docx258 heterodimer, DQ2.5 / one copy of DQA1*05, DQ2 half heterodimer, and DQ2.5 TrHETERO.

22. The computer-implemented method according to any one of the claims5 19 – 21, wherein step (b) further comprises:identifying said subject as a as a subject having a risk for refractory coeliac disease or as a subject suffering from refractory coeliac disease if the HLA- DQ2 and HLA-DQ8 haplotypes are DQ2.5 / DQ2.5, DQ2.5 / DQ2.3, DQ2.5 / one copy of DQB1*02. 10 23. The computer-implemented method according to any one of the claims19 – 22, wherein a subject having a risk for refractory coeliac disease or asubject suffering from refractory coeliac disease is characterized by a changeof villous height to crypt depth (VH:CrD) ratio between -1.0 to -2.7 15 (-1.0 ≥ VH:CrD ratio ≥ -2.7) from a villous height to crypt depth (VH:CrD) ratio of a comparative subject on gluten-free diet.

24. The computer-implemented method according to any one of the claims19 – 23, wherein for a subject having a risk for refractory coeliac disease or20 suffering from refractory coeliac disease the therapeutic regimen comprises one or more of administering the TG2 inhibitor at a higher dose, administering the TG2 inhibitor at higher frequency, longer duration of treatment, administering a more potent TG2 inhibitor than a therapeuticregimen for a subject not suffering from refractory coeliac disease. 25 25. The computer-implemented method according to any one of the claims19 – 24, wherein the therapy regimen comprises TG2 inhibitor at a dailydose between 25 mg – 1000 mg, more preferably between 25 mg – 250mg, preferably between 25 mg – 500 mg, most preferably between30 30 mg – 100 mg.

26. The computer-implemented method according to any one of the claims19 – 25, wherein the therapy regimen preferably comprises TG2 inhibitor ata daily dose between 150 mg – 250 mg, more preferably between 160 mg –35 240 mg, more preferably between 170 mg – 230 mg, more preferablybetween 180 mg – 220 mg, more preferably between 190 mg – 210 mg,most preferably comprises TG2 inhibitor at a daily dose of 200 mg.DFP-P04535WO10 Application (final).docx259 27. The computer-implemented method according to any one of the claims1 – 26, wherein the transglutaminase 2 inhibitor is a reversibletransglutaminase 2 inhibitor or an irreversible transglutaminase 2 inhibitor. 5 28. The computer-implemented method according to any one of the claims1 – 27, wherein the transglutaminase 2 inhibitor is (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1- methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate (Compound 1): 10Compound 1 29. The computer-implemented method according to any one of the claims15 1 – 28, wherein the therapy regimen comprises at least the use of apharmaceutical composition comprising the TG2 inhibitor as an activeingredient, together with at least one pharmaceutically acceptable carrier, excipient and / or diluent in the treatment of celiac disease of said subject,preferably wherein the pharmaceutical composition is a systemic formulation.20 DFP-P04535WO10 Application (final).docx

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