Method for identifying and characterizing an Anti-modified protein antibody associated with a pathological condition related to or caused by inflammation or a dysregulated immune system

Abstract

The invention pertains to a method for identifying, or characterizing specific autoantibodies, associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, comprising: preparing modified protein neo-structure fragments, wherein specific protein neo-structure fragment and the specific antibody are connected to the inflammation or the dysregulated immune system are identified. Also provided are antibodies specifically binding to a modified protein neo-structure associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, a pharmaceutical composition, a method of diagnosing a pathological condition, a method of stimulating an immune response, a method of inhibiting a pathological immune response, a method for modulating an inflammatory response, a method of treating a pathological condition and a method for treating a disease by administering said antibody.

Description

[0001] METHOD FOR IDENTIFYING AND CHARACTERIZING AN ANTI-MODIFIED PROTEIN ANTIBODY ASSOCIATED WITH A PATHOLOGICAL CONDITION RELATED TO OR CAUSED BY INFLAMMATION OR A DYSREGULATED IMMUNE SYSTEM Field of the Invention This invention pertains in general to the field of characterization of modified proteins / neo-structures. In particular, immunoregulatory modified protein neo-structures generated by proteolytic degradation or denaturation of proteins in inflammatory conditions. Further, a method for identifying and characterizing anti-modified protein antibodies (AMPA) associated with a pathological condition. Background of the Invention Several disease conditions are characterized by a pathogenic, inflammatory activation of the immune system, e.g. inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), psoriasis and other so-called chronic inflammatory diseases or autoimmune diseases. In addition, a dysregulated inflammatory activity of major importance for disease development and maintenance is found in cancer, severe infections (sepsis and septic shock), type 2 diabetes, the metabolic syndrome, neurodegenerative diseases and cardiovascular disease. The understanding of regulation of the immune system in these conditions is far from complete, which complicates the development of effective treatment methods. The crucial dysregulatory immune mechanisms which need to be controlled are largely still unknown. It thus seems as if known, normal direct cellular interaction of immune cells or their production of cytokines or chemokines is not enough to explain the type of dysregulation of the immune system seen in the diseases mentioned above. Thus, it seems there is a need for understanding of regulation of the immune system in disease conditions characterized by a pathogenic, inflammatory activation. Summary of the Invention Accordingly, the present invention preferably seeks to mitigate, alleviate or eliminate one or more of the above-identified deficiencies in the art and disadvantages singly or in any combination and solves at least the above mentioned problems by providing a method for identifying, or characterizing specific autoantibodies, associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, comprising - preparing modified protein neo-structure fragments, - incubating a body fluid sample from a healthy individual (control) with said modified protein neo-structure fragments, -identifying, characterizing, and / or quantifying any autoantibodies binding to the modified protein neo-structure fragments, - incubating a body fluid sample from a patient with inflammation or a dysregulated immune system with the same modified protein neo-structure fragments, - identifying, characterizing and / or quantifying any specific autoantibodies binding to the modified protein neo- structure fragments, and - correlating or comparing the levels or amount or type or sequence of the captured autoantibodies for healthy individuals with the levels or amount or type or sequence of the captured autoantibodies from patients with inflammation or a dysregulated immune system for each protein neo-structure fragment, wherein different or altered specific autoantibody levels or amount or type or sequence of the captured autoantibodies between the healthy individual and a patient with normal or dysregulated immune system or inflammation indicates that both the specific protein neo-structure fragment and the specific antibody are connected to the inflammation or the dysregulated immune system. In a further aspect of the invention, the method, optionally further comprises the step of affinity purifying the captured specific autoantibodies connected to the inflammation or the dysregulated immune system, incubating a body fluid from a patient with inflammation or a dysregulated immune system with said affinity purified specific autoantibodies, and identifying, characterizing and / or quantifying any modified protein neo-structure fragments binding to said specific autoantibodies, wherein the identified specific protein neo-structure fragment can be connected to the inflammation or the dysregulated immune system. In a further aspect of the invention, the specific autoantibodies are anti- modified protein antibodies (AMPA). In a further aspect of the invention, the modified protein neo-structure fragments are albumin neo-structures. In one further aspect of the invention. the modified protein neo-structure fragments are the result of enhanced proteolytic fragmentation and / or denaturing in an inflammatory tissue and / or a malignant tumour, resulting in a conformational change of a normally occurring serum protein. In one further aspect of the invention, the modified protein neo-structure fragments are from an immune cell surface binding modified protein. In one further aspect of the invention, the modified protein neo-structure fragments are derived from human serum albumin and can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cell. In a further aspect of the invention, the body fluid sample is selected from or derived from whole blood or fractions thereof, blood plasma, blood serum, lymph fluid, urine, cerebrospinal fluid, saliva, exudates such as synovial fluid, ascites or pleural effusions or tissues including biopsies / samples from infectious or inflamed tissues, lymph nodes, or tumours including the tissue microenvironment. In a further aspect of the invention, the body fluid sample is heat inactivated before the incubation, whereby any autoantibodies that are part of immune complexes (IC) are released and become free / unbound autoantibodies into the body fluid sample. In a further aspect of the invention, the heat activation uses a temperature of between 50 to 70oC and an incubation time of between 5 to 60 minutes, such as a temperature of 50 to 60oC and an incubation time of 15 to 45 minutes. In one further aspect of the invention, one or more of the methods described above utilize protein G beads to capture any IgG and immune complexes in the body fluid sample. In a further aspect of the invention, the pathological condition related to or caused by inflammation or a dysregulated immune system is an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or a cancer, such as a colorectal cancer or a head and neck cancer. In one further aspect of the invention, the pathological condition related to or caused by inflammation or a dysregulated immune system is an infectious diseases selected from the group consisting of: a severe infection caused by any microbe, sepsis, septic shock and a severe viral infection, such as Covid-19. In one further aspect of the invention, the modified protein neo-structure fragments and autoantibodies have the capacity to dysregulate or normalize the function of the immune system and thereby cause or alleviate severe symptoms or play a pathogenic role in the pathological condition. In one further aspect of the invention, the modified protein neo-structure fragment has an amino acid sequence of between 10 to 100 AA length, such as 15 to 50 AA length and comprises (or comprises a fragment of) or is selected from, SEQ ID NO: 1 (FSALEVDETYVPKEFNAETFTFHAC) or SEQ ID NO: 2 (VFDEFKPLVEEPQNLIK), or an amino acid sequence having a % sequence identity (SI) of at least 80%, such as at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% SI to SEQ ID NO: 1 or SEQ ID NO: 2 or an amino acid sequence having the sequence of SEQ ID NO: 1 or 2, wherein any one, two, three, or four amino acids are substituted, preferably with a conservative amino acid substitution. Also provided is an antibody or binding fragment thereof which specifically binds to a modified protein neo-structure associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, preferably an antibody isolated or obtained using any one of the aforementioned methods described above. In one further aspect of the invention, the antibody or binding fragment thereof blocks, inhibits, eliminates or decreases immunoregulatory activity of said modified protein neo-structure fragment. In one further aspect of the invention, the antibody or binding fragment thereof is a monoclonal antibody, recombinant monoclonal antibody or a recombinant polyclonal antibody. Further, a monoclonal antibody, recombinant monoclonal antibody or a recombinant polyclonal antibody, or binding fragment thereof wherein the antibody or binding fragment thereof is an anti-modified protein human or humanized antibody or binding fragment thereof, which blocks, eliminates or decreases the activity of an immunoregulatory anti-modified protein associated with a pathological condition related to or caused by inflammation or a dysregulated immune system in a subject is provided. In one further aspect of the invention, the immunoregulatory anti-modified protein is an immune cell surface binding modified protein. In one further aspect of the invention, the immunoregulatory anti-modified protein is derived from a human serum albumin, which can modify cytokine production, expression of cell surface structures or immune cell function. In one further aspect of the invention, the immunoregulatory modified protein is derived from a human serum albumin, which can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cells. Also provided is a pharmaceutical composition comprising the antibody or binding fragment thereof and a pharmaceutically acceptable carrier, excipient or stabilizer. Further, a method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein in a body fluid sample from a patient, modified proteins and / or autoantibodies that have been linked to a specific pathological condition using the methods describe above are identified and determined, whereby the presence of such a modified protein neo-structure fragment and / or autoantibody binding to the modified protein neo-structure fragment is used to identify that the patient suffers from a specific pathological condition, such as a cancer, inflammation or a dysregulated immune system. In one further aspect of the invention, the occurrence of a modified protein neo-structure fragment and / or an autoantibody binding to the modified protein neo- structure fragment is used to establish the prognosis of the patient suffering from a specific pathological condition, such as a cancer, preferably a colorectal cancer or a head and neck cancer. Also provided is a method of stimulating an immune response in a subject, comprising administering to a subject in need thereof an antibody or a binding fragment thereof, such as an scFv domain, which can be presented on a cell (e.g., a chimeric antigen receptor T cell) or a support or a pharmaceutical composition comprising said antibody or binding fragment thereof in an amount effective to stimulate or control the immune response, wherein the antibody and / or the binding fragment thereof is identified, characterized, and / or generated using one or more of the procedures described herein. Further embodiments include methods of inhibiting a pathological immune response in a subject, comprising administering to a subject in need thereof an antibody or a binding fragment thereof such as an scFv domain, which can be presented on a cell (e.g., a chimeric antigen receptor T cell) or a support in an amount effective to inhibit the immune response, wherein the antibody and / or the binding fragment thereof is, preferably identified, characterized, and / or generated using one or more of the procedures described herein. Also, contemplated are methods for modulating an inflammatory response in a subject, comprising administering to the subject an effective amount of an antibody or binding fragment thereof such as an scFv domain, which can be presented on a cell (e.g., a chimeric antigen receptor T cell) or a support, wherein the antibody or binding fragment thereof is a human or humanized antibody or binding fragment thereof, which blocks, inhibits, eliminates or decreases the activity of an immunoregulatory modified protein neo-structure fragment in the subject and, wherein the antibody and / or the binding fragment thereof is preferably identified, characterized, and / or generated using one or more of the procedures described herein. Further embodiments concern methods of treating, inhibiting, or ameliorating a pathological condition related to or caused by inflation or a dysregulated immune system, such as a cancer (e.g., a colorectal cancer or a head and neck cancer), comprising administering to a subject in need thereof an antibody or binding fragment thereof such as an scFv domain, which can be presented on a cell (e.g., a chimeric antigen receptor T cell) or a support or a pharmaceutical composition comprising said antibody or binding fragment thereof in an amount effective to treat or inhibit a pathological condition related to or caused by a dysregulated immune system, wherein the antibody and / or the binding fragment thereof is, preferably identified, characterized, and / or generated using one or more of the procedures described herein. Also, a method for treating, inhibiting, or ameliorating a disease, such as a cancer, e.g., a colorectal cancer or head and neck cancer, by blocking, inhibiting, eliminating or decreasing the activity of an immunoregulatory modified protein neo- structure fragment in a subject, by administering to the subject an effective amount of a monoclonal or a recombinant polyclonal antibody or binding fragment thereof such as an scFv domain, which can be presented on a cell (e.g., a chimeric antigen receptor T cell) or a support or a pharmaceutical composition comprising said antibody or binding fragment thereof, wherein the antibody and / or the binding fragment thereof is preferably identified, characterized, and / or generated using one or more of the procedures described herein. Further is provided a method for identifying and characterizing immune parameters related to an autoantibody binding to a modified protein neo-structure fragment, or a modified protein neo-structure fragment, wherein in an isolated sample of immune cells from a patient with a pathological condition; the isolated immune cells are divided into two cell portions; the first immune cell portion is incubated with antibodies with the same specificity as autoantibodies associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, in order to remove cell bound modified protein neo-structures; the first and second immune cell portion are cultured separately in a medium for at least one day, and the production of cytokines in the medium or the expression of cell surface markers or the function of each immune cell portion is determined. Also provided is a method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein immune parameters related to a modified protein neo-structure fragment are identified and characterized in an isolated sample of immune cells from a patient with a pathological condition, whereby it can be determined which modified protein neo-structures are involved in immunoregulation in the patient. Further, is provided a method for identifying and characterizing surface cell receptor expression related to an autoantibody or modified protein neo-structure, wherein in an isolated sample of immune cells from a patient with a pathological condition; the isolated immune cells are divided into two cell portions, where the second immune cell portion is incubated with antibodies with the same specificity as autoantibodies associated with a pathological condition related to or caused by a dysregulated immune system, in order to remove cell bound modified protein neo- structures; cells from the first and the second immune cell portion are harvested; and expression of surface cell markers are determined for the harvested cells from the first immune cell portion and for the second immune cell portion, or the first and second immune cell portion are cultured separately in a medium for at least one day, and expression of surface cell markers are determined for these cells from the first immune cell portion and for the second immune cell portion, whereby any change in expression of surface cell receptors between the harvested immune cells of the first cell portion, comprising cell bound modified protein neo-structures, and the harvested immune cells of the second portion, where autoantibodies has removed cell bound modified protein neo-structures, can be determined. Additional embodiments are provided in the alternatives set forth below. 1. A method for identifying, or characterizing specific autoantibodies, associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, comprising: - preparing modified protein neo-structure fragments, - incubating a body fluid sample from a healthy individual (control) with said modified protein neo-structure fragments, - identifying, characterizing, and / or quantifying any autoantibodies binding to the modified protein neo-structure fragments, - incubating a body fluid sample from a patient with inflammation or a dysregulated immune system with the same modified protein neo-structure fragments, - identifying, characterizing and / or quantifying any specific autoantibodies binding to the modified protein neo-structure fragments, and - correlating or comparing the levels or amount or type or sequence of the captured autoantibodies for healthy individuals and with the levels or amount or type or sequence of the captured autoantibodies from patients with inflammation or a dysregulated immune system for each protein neo-structure fragment, wherein different or altered specific autoantibody level or amount or type or sequence of the captured autoantibodies between the healthy individual and a patient with a normal or dysregulated immune system or inflammation indicates that both the specific protein neo-structure fragment and the specific antibody are connected to the inflammation or the dysregulated immune system. 2. The method according to alternative 1, wherein the method further comprises: affinity purifying the captured specific autoantibodies connected to the inflammation or the dysregulated immune system, incubating a body fluid from a patient with inflammation or a dysregulated immune system with said affinity purified specific autoantibodies, and identifying, characterizing and quantifying any modified protein neo-structure fragments binding to said specific autoantibodies, wherein the identified specific protein neo-structure fragment can be connected to the inflammation or the dysregulated immune system. 3. The method according to alternative 1 or 2, wherein the specific autoantibodies are anti-modified protein antibodies (AMPA). 4. The method according to any one of alternatives 1 to 3, wherein the modified protein neo-structure fragments are albumin neo-structures. 5. The method according to any one of alternatives 1 to 4, wherein the protein neo-structure fragments may be bound to chips, beads ELISA plates or peptide arrays. 6. The method for according to any one of alternatives 1 to 5, wherein the body fluid sample is selected from or derived from whole blood or fractions thereof, blood plasma, blood serum, lymph fluid, urine, cerebrospinal fluid, saliva, exudates such as synovial fluid, ascites or pleural effusions or tissues including biopsies / samples from infectious or inflamed tissues, lymph nodes, or tumours including the tissue microenvironment. 7. The method according to any one of alternatives 1 to 6, wherein the body fluid sample is a blood plasma, sera or urine sample. 8. The method according to any one of alternatives 1 to 7, wherein the body fluid sample is heat inactivated before the incubation, whereby any autoantibodies that are part of immune complexes (IC) are released and become free / unbound autoantibodies into the body fluid sample. 9. The method according to alternative 8, wherein the heat activation uses a temperature of between 50 to 70oC and an incubation time of between 5 to 60 minutes, such as a temperature of 50 to 60oC and an incubation time of 15 to 45 minutes. 10. The method according to any one of alternatives 1 to 9, wherein protein G beads are used to capture any IgG and immune complexes in the body fluid sample. 11. The method according to alternative 10, wherein, wherein any autoantibodies part of any IgG and immune complexes are released by acidic elution and then captured by a surplus of modified protein neo-structures bound to beads during neutralization of the eluate. 12. The method according to any one of alternatives 1 to 11, the modified protein neo-structure fragments are the result of enhanced proteolytic fragmentation and / or denaturing in an inflammatory tissue and / or a malignant tumour, resulting in a conformational change of a normally occurring serum protein. 13. The method according to any one of alternatives 1 to 12, wherein the modified protein neo-structure fragments is derived from any protein that after modification bind to cellular receptors, e.g. albumin, fibrinogen or extracellular matrix (ECM) proteins. 14. The method according to any one of alternatives 1 to 13, wherein the modified protein neo-structure fragments are from a immune cell surface binding modified protein. 15. The method according to any one of alternatives 1 to 14, wherein the modified protein neo-structure fragments are derived from human serum albumin. 16. The method according to any one of alternatives 1 to 15, wherein the modified protein neo-structure fragments are derived from human serum albumin and can modify cytokine production, expression of cell surface structures or immune cell function. 17. The method according to any one of alternatives 1 to 16, wherein the modified protein neo-structure fragments are derived from human serum albumin and can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cells. 18. A method according to alternative 17, wherein the IL-6 production is determined using one or more standard tests. 19. The method according to any one of alternatives 1 to 18, wherein the pathological condition related to or caused by inflammation or a dysregulated immune system is an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or a cancer, such as a colorectal cancer or a head and neck cancer, such as cancer types associated with IL-6, such as Hematological Cancers or Solid Tumor Cancers, such as multiple myeloma, leukemia (such as Acute myeloid leukemia (AML)), Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Lymphoma (such as Hodgkin lymphoma or Non-Hodgkin lymphoma), Breast cancer, Prostate cancer, Lung cancer (such as Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC)), Colorectal cancer, Pancreatic cancer, Ovarian cancer, Liver cancer (Hepatocellular carcinoma), Renal cell carcinoma, Gastric cancer, Bladder cancer, Head and neck cancers (such as Oral cancer, Pharyngeal cancer, Laryngeal cancer), and Sarcomas (such as Osteosarcoma, Ewing sarcoma or Soft tissue sarcoma). 20. The method according to any one of alternatives 1 to 19, wherein the pathological condition related to or caused by inflammation or a dysregulated immune system is an infectious diseases selected from: severe infection caused by any microbe, sepsis, septic shock or severe viral infection, such as Covid-19. 21. The method according to any one of alternatives 1 to 20, wherein the modified protein neo-structure fragments and autoantibodies have the capacity to dysregulate or normalize the function of the immune system and thereby cause or alleviate severe symptoms or play a pathogenic role in the pathological condition. 22. The method for according to any one of alternatives 1 to 21, wherein the dysregulation of the immune system is characterized by immune overstimulation / hyperstimulation, including a cytokine storm, and / or any type of immune suppression. 23. The method according to any one of alternatives 1 to 22, wherein the modified protein neo-structure fragment is an albumin neo-structure with known amino acid sequence. 24. The method according to any one of alternatives 1 to 23, wherein the modified protein neo-structure fragments has an amino acid sequence of between 10 to 100 AA length, such as 15 to 50 AA length and comprises (or comprises a fragment of) or is selected from SEQ ID NO: 1 (FSALEVDETYVPKEFNAETFTFHAC) or SEQ ID NO: 2 (VFDEFKPLVEEPQNLIK), or having a % sequence identity (SI) of at least 80%, such as at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with SEQ ID NO: 1 or SEQ ID NO: 2, an amino acid sequence having the sequence of SEQ ID NO: 1 or 2, wherein any one, two, three, or four amino acids are substituted, preferably with a conservative amino acid substitution. 25. An antibody or binding fragment thereof, which specifically binds to a modified protein neo-structure fragment associated with a pathological condition related to or caused by inflammation or a dysregulated immune system according to any one of alternatives 1 to 24. 26. The antibody or binding fragment thereof according to alternative 25, wherein the antibody or binding fragment thereof blocks, inhibits, eliminates or decreases immunoregulatory activity of said modified protein neo-structure fragment. 27. The antibody or binding fragment thereof according to alternative 25 or 26, wherein the antibody or binding fragment thereof is a monoclonal antibody or binding fragment thereof, a recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof. 28. A monoclonal antibody, recombinant monoclonal antibody or a recombinant polyclonal antibody, or a binding fragment thereof, wherein the antibody or binding fragment thereof is an anti-modified protein human or humanized antibody or binding fragment thereof, which blocks, eliminates or decreases the activity of an immunoregulatory anti-modified protein associated with a pathological condition related to or caused by inflammation or a dysregulated immune system in a subject. 29. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof according to alternative 28, wherein the immunoregulatory anti-modified protein is an immune cell surface binding modified protein. 30. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof according to alternative 28 or 29, wherein the immunoregulatory anti-modified protein is derived from a human serum albumin, which can modify cytokine production, expression of cell surface structures or immune cell function. 31. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof according to any one of alternatives alternative 28 to 30, wherein the immunoregulatory modified protein is derived from a human serum albumin, which can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cells. 32. A pharmaceutical composition comprising the antibody or binding fragment thereof according to any of alternatives 25 to 31 and a pharmaceutically acceptable carrier, excipient or stabilizer. 33. A method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein in a body fluid sample from a patient, modified proteins and / or autoantibodies that have been linked to a specific pathological condition using the method of alternatives 1 to 24 are identified and determined, whereby the presence of such a modified protein neo-structure fragment and / or autoantibody binding to the modified protein neo-structure fragment is used to identify that the patient suffers from the specific pathological condition, such as a cancer, inflammation or a dysregulated immune system. 34. The method according to alternative 33, wherein the occurrence of a modified protein neo-structure fragment and / or an autoantibody binding to the modified protein neo-structure fragment is used to establish the prognosis of the patient suffering from the specific pathological condition, such as a cancer, preferably a colorectal cancer or a head and neck cancer. 35. A method of stimulating an immune response in a subject, comprising administering to a subject in need thereof an antibody or a binding fragment thereof, according to any of alternatives 25 to 31, or a pharmaceutical composition comprising said antibody or binding fragment thereof according to alternative 32, in an amount effective to stimulate or control the immune response. . A method of inhibiting a pathological immune response in a subject, comprising administering to a subject in need thereof an antibody or binding fragment thereof according to any of alternatives 25 to 31, in an amount effective to inhibit the immune response. . A method for modulating an inflammatory response in a subject, comprising administering to the subject an effective amount of an antibody or binding fragment thereof according to any of alternatives 25 to 31, wherein the antibody or binding fragment thereof is a human or humanized antibody or binding fragment thereof, which blocks, inhibits, eliminates or decreases the activity of an immunoregulatory modified protein neo-structure fragment in the subject. . A method of treating or inhibiting a pathological condition related to or caused by inflation or a dysregulated immune system, comprising administering to a subject in need thereof an antibody or binding fragment thereof of any of alternatives 25 to 31, or a pharmaceutical composition according to alternative 32, in an amount effective to treat a pathological condition related to or caused by a dysregulated immune system. . The method according to alternative 38 wherein the pathological condition related to or caused by inflammation or a dysregulated immune system is an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or a cancer, such as a colorectal cancer or a head and neck cancer, such as cancer types associated with IL-6, such as Hematological Cancers or Solid Tumor Cancers, such as multiple myeloma, leukemia (such as Acute myeloid leukemia (AML)), Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Lymphoma (such as Hodgkin lymphoma or Non-Hodgkin lymphoma), Breast cancer, Prostate cancer, Lung cancer (such as Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC)), Colorectal cancer, Pancreatic cancer, Ovarian cancer, Liver cancer (Hepatocellular carcinoma), Renal cell carcinoma, Gastric cancer, Bladder cancer, Head and neck cancers (such as Oral cancer, Pharyngeal cancer, Laryngeal cancer), and Sarcomas (such as Osteosarcoma, Ewing sarcoma or Soft tissue sarcoma). 40. The method according to any one of alternatives 38 to 39, wherein the pathological condition is and infectious diseases selected from severe infection caused by any microbe, in particular sepsis, septic shock or severe viral infection, such as Covid-19. 41. The method according to any one of alternatives 38 to 40, wherein the antibody or binding fragment thereof specifically binds to an immunoregulatory albumin neo-structure. 42. A method for treating or inhibiting, or ameliorating a disease by blocking, inhibiting, eliminating or decreasing the activity of an immunoregulatory modified protein neo-structure fragment in a subject, by administering to the subject an effective amount of a monoclonal or a recombinant polyclonal antibody or binding fragment thereof according to any one of alternatives 25 to 31 or a pharmaceutical composition according to alternative 32. 43. A method for identifying and characterizing immune parameters related to an autoantibody binding to a modified protein neo-structure fragment, or a modified protein neo-structure fragment, wherein in an isolated sample of immune cells from a patient with a pathological condition; the isolated immune cells are divided into two cell portions; the first immune cell portion is incubated with antibodies with the same specificity as autoantibodies associated with a pathological condition related to or caused by inflammation or a dysregulated immune system according to any one of alternatives 1 to 24, in order to remove cell bound modified protein neo-structures; the first and second immune cell portion are cultured separately in a medium for at least one day, and the production of cytokines in the medium or the expression of cell surface markers or the function of each immune cell portion is determined. 44. The method according to alternative 43, wherein epitope specific autoantibodies or antibodies with the same specificity are used to remove cell bound modified protein neo-structure fragments, whereby the immune parameter related to only one neo-structure will be analyzed. 45. The method according to alternative 43 or 44, wherein total, all types of AMPA including all released antibodies in the serum or antibodies with the corresponding specificities are used to remove cell bound modified protein neo-structure fragments, whereby the total dysregulation by immunogenic immunoregulatory neo-structure fragments in that particular patient will be analyzed. 46. The method according to alternative 45, wherein the antibodies are produced as recombinant polyclonal antibodies. 47. A method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein immune parameters related to a modified protein neo-structure fragment are identified and characterized in an isolated sample of immune cells from a patient with a pathological condition using the method according to any one of alternatives 43 to 46, whereby it can be determined which modified protein neo-structures are involved in immunoregulation in the patient. 48. A method for identifying and characterizing surface cell receptor expression related to an autoantibody or modified protein neo-structure, wherein in an isolated sample of immune cells from a patient with a pathological condition; the isolated immune cells are divided into two cell portions, where the second immune cell portion is incubated with antibodies with the same specificity as autoantibodies associated with a pathological condition related to or caused by a dysregulated immune system according to any one of alternatives 1 to 24, in order to remove cell bound modified protein neo-structures; cells from the first and the second immune cell portion are harvested; and expression of surface cell markers are determined for the harvested cells from the first immune cell portion and for the second immune cell portion, or the first and second immune cell portion are cultured separately in a medium for at least one day, and expression of surface cell markers are determined for these cells from the first immune cell portion and for the second immune cell portion, whereby any change in expression of surface cell receptors between the harvested immune cells of the first cell portion, comprising cell bound modified protein neo-structures, and the harvested immune cells of the second portion, where antibodies has removed cell bound modified protein neo-structures, can be determined. . The method according to alternative 48, wherein the expression of cell surface markers is determined using Flow Cytometry. . The method according to alternative 48 or 49, wherein epitope specific antibodies with the same specificity as autoantibodies are used to remove cell bound modified protein neo-structures, or total autoantibodies including all released antibodies in the serum are used to remove cell bound modified protein neo-structures. . A method for identifying, isolating, characterizing or quantifying autoantibodies specific for one or more modified protein neo-structure fragments associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, comprising: - preparing one or more modified protein neo-structure fragments, - incubating a body fluid sample from a healthy individual (control) with said one or more modified protein neo-structure fragments, and - identifying, isolating, characterizing, or quantifying autoantibodies from the body fluid sample from the healthy individual binding to the one or more modified protein neo-structure fragments, or - incubating a body fluid sample from a patient having inflammation or a dysregulated immune system with said one or more modified protein neo-structure fragments, and - identifying, isolating, characterizing or quantifying autoantibodies from the body fluid sample from the patient having inflammation or a dysregulated immune system, which bind to the one or more modified protein neo-structure fragments, - optionally, comparing the levels of captured autoantibodies for healthy individuals and patients having inflammation or a dysregulated immune system for each one or more modified protein neo-structure fragment, wherein a different / altered specific autoantibody level between the healthy individual and a patient having inflammation, or a dysregulated immune system indicates that both the modified protein neo-structure fragment and the isolated antibody are associated with a pathological condition related to or caused by inflammation or a dysregulated immune system. The method according to alternative 1, wherein the method further comprises: - affinity purifying the autoantibodies from the healthy individuals and / or the patients with inflammation or a dysregulated immune system, which bind to the one or more modified protein neo-structure fragments and, - optionally, incubating a body fluid from a patient with inflammation or a dysregulated immune system with said affinity purified specific autoantibodies and, - optionally, identifying, isolating, characterizing and / or quantifying the modified protein neo-structure fragments binding to said affinity purified specific autoantibodies. The method according to alternative 51 or 52, wherein the specific autoantibodies are anti-modified protein antibodies (AMPA). The method according to any one of alternatives 51 to 53, wherein the modified protein neo-structure fragments are albumin neo-structures. The method according to any one of alternatives 51 to 54, wherein the modified protein neo-structure fragments are bound to chips, beads ELISA plates or peptide arrays. The method for according to any one of alternatives 51 to 55, wherein the body fluid sample is selected from or derived from whole blood or fractions thereof, blood plasma, blood serum, lymph fluid, urine, cerebrospinal fluid, saliva, exudates such as synovial fluid, ascites or pleural effusions or tissues including biopsies / samples from infectious or inflamed tissues, lymph nodes, or tumours including the tissue microenvironment. The method according to any one of alternatives 51 to 56, wherein the body fluid sample is a blood plasma, sera or urine sample. The method according to any one of alternatives 51 to 57, wherein the body fluid sample is heat inactivated before the incubation under conditions sufficient to release autoantibodies that are part of immune complexes (IC) so as to produce free / unbound autoantibodies in the body fluid sample. The method according to alternative 58, wherein the conditions sufficient to release autoantibodies that are part of immune complexes (IC) comprise heat activation at temperature of between 50 to 70oC and an incubation time of between 5 to 60 minutes, such as a temperature of 50 to 60oC and an incubation time of 15 to 45 minutes. The method according to any one of alternatives 51 to 59, wherein protein G beads are used to capture IgG and immune complexes in the body fluid sample. The method according to alternative 60, wherein, wherein autoantibodies, which are part of IgG and immune complexes are released by acidic elution and captured with modified protein neo-structures bound to beads, preferably during neutralization of the eluate. The method according to any one of alternatives 51 to 61, wherein the modified protein neo-structure fragments are produced by enhanced proteolytic fragmentation and / or denaturing in an inflammatory tissue and / or a malignant tumour, resulting in a conformational change of a serum protein. The method according to any one of alternatives 51 to 62, wherein the modified protein neo-structure fragments are derived from a protein that after modification binds to cellular receptors, e.g. albumin, fibrinogen or one or more extracellular matrix (ECM) proteins. The method according to any one of alternatives 51 to 63, wherein the modified protein neo-structure fragments are from an immune cell surface binding modified protein. The method according to any one of alternatives 51 to 64, wherein the modified protein neo-structure fragments are derived from human serum albumin. The method according to any one of alternatives 51 to 65, wherein the modified protein neo-structure fragments are derived from human serum albumin and can modify cytokine production, expression of cell surface structures or an immune cell function. The method according to any one of alternatives 51 to 66, wherein the modified protein neo-structure fragments are derived from human serum albumin and can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cells. 68. A method according to alternative 17, wherein the IL-6 production is determined using one or more standard tests. 69. The method according to any one of alternatives 51 to 68, wherein the pathological condition related to or caused by inflammation, or a dysregulated immune system is an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or a cancer, such as colorectal cancer or a head and neck cancer, such as cancer types associated with IL-6, such as Hematological Cancers or Solid Tumor Cancers, such as multiple myeloma, leukemia (such as Acute myeloid leukemia (AML)), Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Lymphoma (such as Hodgkin lymphoma or Non-Hodgkin lymphoma), Breast cancer, Prostate cancer, Lung cancer (such as Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC)), Colorectal cancer, Pancreatic cancer, Ovarian cancer, Liver cancer (Hepatocellular carcinoma), Renal cell carcinoma, Gastric cancer, Bladder cancer, Head and neck cancers (such as Oral cancer, Pharyngeal cancer, Laryngeal cancer), and Sarcomas (such as Osteosarcoma, Ewing sarcoma or Soft tissue sarcoma). 70. The method according to any one of alternatives 51 to 69, wherein the pathological condition related to or caused by inflammation, or a dysregulated immune system is an infectious diseases selected from: a severe infection caused by a microbe, sepsis, septic shock or a viral infection, such as Covid- 19. 71. The method according to any one of alternatives 51 to 70, wherein the modified protein neo-structure fragments and autoantibodies have the capacity to dysregulate or normalize the function of the immune system and thereby cause or alleviate severe symptoms or play a pathogenic role in the pathological condition. 72. The method for according to any one of alternatives 51 to 71, wherein the dysregulation of the immune system is characterized by immune overstimulation or hyperstimulation, such as a cytokine storm, or immune suppression. 73. The method according to any one of alternatives 51 to 72, wherein the one or more modified protein neo-structure fragments are an albumin neo-structure with a known amino acid sequence. 74. The method according to any one of alternatives 51 to 73, wherein the one or more modified protein neo-structure fragments have an amino acid sequence of between 15 to 50 amino acids in length and have a sequence comprising or consisting of SEQ ID NO: 1 (FSALEVDETYVPKEFNAETFTFHAC) or SEQ ID NO: 2 (VFDEFKPLVEEPQNLIK), an amino acid sequence having a % sequence identity (SI) of at least 80%, such as at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with SEQ ID NO: 1 or SEQ ID NO: 2 or an amino acid sequence having the sequence of SEQ ID NO: 1 or 2, wherein any one, two, three, or four amino acids are substituted, preferably with a conservative amino acid substitution. 75. An antibody or binding fragment thereof such as an scFv domain, which can be presented on a cell (e.g., a chimeric antigen receptor T cell) or a support, wherein said antibody or binding fragment thereof specifically binds to a modified protein neo-structure fragment associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, isolated or characterized according to any one of alternatives 51 to 74, such as a monoclonal antibody or binding fragment thereof, a recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof, which specifically binds to an amino acid sequence comprising or consisting of SEQ ID NO: 1 (FSALEVDETYVPKEFNAETFTFHAC) or SEQ ID NO: 2 (VFDEFKPLVEEPQNLIK), an amino acid sequence having a % sequence identity (SI) of at least 80%, such as at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with SEQ ID NO: 1 or SEQ ID NO: 2 or an amino acid sequence having the sequence of SEQ ID NO: 1 or 2, wherein any one, two, three, or four amino acids are substituted, preferably with a conservative amino acid substitution. 76. The antibody or binding fragment thereof according to alternative 75, wherein the antibody or binding fragment thereof blocks, inhibits, eliminates or decreases immunoregulatory activity of said one or more modified protein neo-structure fragments. 77. The antibody or binding fragment thereof according to alternative 75 or 76, wherein the antibody or binding fragment thereof is a monoclonal antibody or binding fragment thereof, a recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof. 78. A monoclonal antibody, recombinant monoclonal antibody or a recombinant polyclonal antibody, or a binding fragment thereof, wherein the antibody or binding fragment thereof is an anti-modified protein human or humanized antibody or binding fragment thereof, which blocks, eliminates or decreases the activity of an immunoregulatory anti-modified protein associated with a pathological condition related to or caused by inflammation or a dysregulated immune system in a subject isolated by any one of the alternatives 51 to 74. 79. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or a binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof according to alternative 78, wherein the immunoregulatory anti-modified protein is an immune cell surface binding modified protein. 80. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or a binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof according to alternative 78 or 79, wherein the immunoregulatory anti-modified protein is derived from a human serum albumin, which can modify cytokine production, expression of cell surface structures or immune cell function. 81. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or a binding fragment thereof according to any one of alternatives alternative 78 to 80, wherein the immunoregulatory modified protein is derived from a human serum albumin, which can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cells. 82. A pharmaceutical composition comprising the antibody or binding fragment thereof according to any of alternatives 75 to 81 and a pharmaceutically acceptable carrier, excipient or stabilizer. 83. A method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein: in a body fluid sample from a patient, modified proteins or autoantibodies that have been linked to a specific pathological condition using the method of alternatives 51 to 74 are identified and determined, whereby: the presence of such a modified protein neo-structure fragment or autoantibody binding to the modified protein neo-structure fragment is used to verify that the patient suffers from the specific pathological condition. 84. The method according to alternative 83, wherein the occurrence of a modified protein neo-structure fragment or an autoantibody binding to the modified protein neo-structure fragment is used to establish the prognosis of the patient suffering from the specific pathological condition. 85. A method of stimulating an immune response in a subject, comprising: administering to a subject in need thereof an antibody or a binding fragment thereof according to any of alternatives 75 to 81, or a pharmaceutical composition according to alternative 82, in an amount effective to stimulate or control the immune response. 86. A method of inhibiting a pathological immune response in a subject, comprising: administering to a subject in need thereof an antibody or binding fragment thereof according to any of alternatives 75 to 81, in an amount effective to inhibit the immune response. 87. A method for modulating an inflammatory response in a subject, comprising: administering to the subject an effective amount of an antibody or binding fragment thereof according to any of alternatives 75 to 81, wherein the antibody or binding fragment thereof is a human or humanized antibody or binding fragment thereof, which blocks, inhibits, eliminates or decreases the activity of an immunoregulatory modified protein neo-structure fragment in the subject. 88. A method of treating or inhibiting a pathological condition related to or caused by inflammation or a dysregulated immune system, comprising administering to a subject in need thereof an antibody or binding fragment thereof of any of alternatives 75 to 81, or a pharmaceutical composition according to alternative 82, in an amount effective to treat or inhibit a pathological condition related to or caused by a dysregulated immune system. 89. The method according to alternative 88 wherein the pathological condition related to or caused by inflammation, or a dysregulated immune system is an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or a cancer, such as colorectal cancer or head and neck cancer, such as cancer types associated with IL-6, such as Hematological Cancers or Solid Tumor Cancers, such as multiple myeloma, leukemia (such as Acute myeloid leukemia (AML)), Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Lymphoma (such as Hodgkin lymphoma or Non-Hodgkin lymphoma), Breast cancer, Prostate cancer, Lung cancer (such as Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC)), Colorectal cancer, Pancreatic cancer, Ovarian cancer, Liver cancer (Hepatocellular carcinoma), Renal cell carcinoma, Gastric cancer, Bladder cancer, Head and neck cancers (such as Oral cancer, Pharyngeal cancer, Laryngeal cancer), and Sarcomas (such as Osteosarcoma, Ewing sarcoma or Soft tissue sarcoma). . The method according to any one of alternatives 88 to 89, wherein the pathological condition is an infectious disease selected from an infection caused by a microbe, in particular sepsis, septic shock or a viral infection, such as Covid-19. . The method according to any one of alternatives 88 to 90, wherein the antibody or binding fragment thereof specifically binds to an immunoregulatory albumin neo-structure. . A method for treating or inhibiting a disease by blocking, inhibiting, eliminating, or decreasing the activity of an immunoregulatory modified protein neo-structure fragment in a subject, by administering to the subject an effective amount of a monoclonal or a recombinant polyclonal antibody or binding fragment thereof according to any one of alternatives 75 to 81 or a pharmaceutical composition according to alternative 82. . A method for identifying and characterizing immune parameters related to an autoantibody binding to a modified protein neo-structure fragment, or a modified protein neo-structure fragment, comprising: preparing two cell portions from an isolated sample of immune cells obtained from a patient that has a pathological condition, incubating a first immune cell portion with antibodies having the same specificity as autoantibodies associated with a pathological condition related to or caused by inflammation or a dysregulated immune system according to any one of alternatives 51 to 74, to remove cell bound modified protein neo- structures; incubating a second immune cell portion, wherein the first and second immune cell portions are cultured separately in a medium for at least one day, and determining the production of one or more cytokines, the expression of one or more cell surface markers or the function of at least one of the prepared immune cell portions. . The method according to alternative 93, wherein epitope specific autoantibodies or antibodies with the same specificity are used to remove cell bound modified protein neo-structure fragments, whereby the immune parameter related to only one neo-structure is analyzed. . The method according to alternative 93 or 94, wherein the total of all types of AMPA including all released antibodies in the serum or antibodies with the corresponding specificities are used to remove cell bound modified protein neo-structure fragments, whereby the total dysregulation by immunogenic immunoregulatory neo-structure fragments in that particular patient will be analyzed. . The method according to alternative 95, wherein the antibodies are produced as recombinant polyclonal antibodies. . A method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein immune parameters related to a modified protein neo-structure fragment are identified and characterized in an isolated sample of immune cells from a patient with a pathological condition using the method according to any one of alternatives 43 to 46, whereby it can be determined which modified protein neo-structures are involved in immunoregulation in the patient. . A method for identifying and characterizing surface cell receptor expression related to an autoantibody or modified protein neo-structure, wherein: dividing an isolated sample of immune cells from a patient having a pathological condition into a first immune cell portion and a second immune cell portion, wherein the second immune cell portion is incubated with antibodies having the same specificity as autoantibodies associated with a pathological condition related to or caused by a dysregulated immune system according to any one of alternatives 51 to 74, in order to remove cell bound modified protein neo-structures; harvesting cells from the first and the second immune cell portions; and determining the expression of surface cell markers on the harvested cells from the first immune cell portion and for the second immune cell portion, or culturing the first and second immune cell portion separately in a medium for at least one day, and determining the expression of surface cell markers on the first immune cell portion and the second immune cell portion, whereby a change in expression of surface cell receptors between the harvested immune cells of the first cell portion, comprising cell bound modified protein neo-structures, and the harvested immune cells of the second portion, wherein the antibodies have removed cell bound modified protein neo-structures, are determined. 99. The method according to alternative 98, wherein the expression of cell surface markers is determined using Flow Cytometry. 100. The method according to alternative 98 or 99, wherein epitope specific antibodies with the same specificity as autoantibodies are used to remove cell bound modified protein neo-structures, or total autoantibodies including all released antibodies in the serum are used to remove cell bound modified protein neo-structures. Brief Description of the Drawings These and other aspects, features and advantages of which the invention is capable of will be apparent and elucidated from the following description of embodiments of the present invention, reference being made to the accompanying drawings, in which Fig.1 is graph showing production of IL-6 in short term cultures of PBMC from healthy individuals after addition of P935 (29935) peptide, a 24 mer with the sequence: HFSALEVDETYVPKEFNAETFTFHAC (SEQ ID NO: 3). Peptide 29930 is an unrelated albumin sequence. The concentration of IL-6 in culture supernatants after 24 hours was measured using the ELISA technique. A representative experiment is shown; Fig.2 is a graph showing the influence of V-8 Staphylococcus aureus protease on the generation of 3028-structures in three different buffer conditions in comparison to buffer controls without protease. Generation of 3028-structures as determined by sandwich enzyme-linked immunosorbent assay (ELISA) of protease degraded samples of human serum albumin under different buffer conditions in comparison to controls with no protease. The samples were incubated for 4 h and 16 h respectively in Buffer 1 (B1) containing 100 mM ammonium acetate at pH 4.0, Buffer 2 (B2) containing 100 mM ammonium bicarbonate at pH 7.8 or Buffer 3 (B3) containing 100 mM sodium phosphate at pH 7.8; Fig.3 is a scan of a gel showing the characterization by SDS-PAGE of albumin fragments generated by Staphylococcus aureus V-8 protease. Generation of albumin fragments as determined by SDS-PAGE in protease (P) degraded samples of human serum albumin under different buffer conditions and in controls with no protease (C). The samples were incubated for 4 h and 16 h respectively in Buffer 1 (B1) containing 100 mM ammonium acetate at pH 4.0, Buffer 2 (B2) containing 100 mM ammonium bicarbonate at pH 7.8 or Buffer 3 (B3) containing 100 mM sodium phosphate at pH 7.8; Fig.4 is a graph showing IL-6 production by PMBC, activated with addition of LPS, 0.05 ng / mL, in the presence of healthy or cancer sera diluted to 10%. Anti-935 antibody or Rabbit IgG at a concentration of 20µg / mL were added to half of the cultures. Sera from healthy controls KA, KK,TK and BD and cancer patients MOSP 31, 35, 36, and LHH 45; Fig.5 is a graph showing IL-6 production of PMBC in presence of IgG depleted healthy or cancer serum at 10% with 20µg / mL Rabbit IgG or anti-935 antibody with 0.05ng / mL LPS (for further explanation see Figure 4); Figure 6. Generation of the albumin neo-structures 3028 and 935 in PBMC cultures from healthy controls and advanced cancer patients. Increasing amounts of albumin (HSA) was added to the cultures. A significantly enhanced amount of both these neo-structures were generated in cultures from cancer patients compared to healthy controls; Fig.7 shows four tissue stains showing the expression of the P935 epitope in 4 different human breast cancers IHC using affinity purified rabbit antibodies. Four different staining patterns are shown. In tumour (A) the 935 structure is mainly expressed in inflammatory cells with macrophage morphology localized in the stroma, in tumour (B) and (C) this neo-structure is widely present in stromal areas and in tumour (D) the stroma and tumour cells show a strong expression of the 935-structure; Fig.8 shows two tissue stains showing the occurrence of albumin neo-structure 935 in two different colorectal cancers. Macrophages in the stroma and stromal matrix areas clearly express the 935-structure whereas tumour cells are mainly negative; Fig.9 shows two tissue stains showing the expression of IL-6 I two colorectal cancers; Fig.10 shows two tissue stains showing the occurrence of albumin neo- structure 3028 in two different colorectal cancers. Positive staining in tumor cell areas, only few scattered positive cells in the storm; Fig.11 is a graph showing the occurrence of AMPA directed against the IL-6 inducing albumin neo-structure 935 in serum or plasma from healthy controls and cancer patients. Serum and plasma from 6 control persons were compared and the antibody titres in the two types of samples were found to be very similar. The antibody titres in sera from one group with advanced, metastatic cancer and one with localized head and neck cancer are shown. Dark bars samples diluted to 10% and grey bars samples diluted to 2% and heat inactivated for 30 minutes at 56oC; Fig.12 is a graph showing the occurrence of AMPA directed against albumin neo-structure 3028, involved in down regulation of normal immune reactivity, in serum or plasma from healthy controls and cancer patients. The full explanation to the Figure is given in Figure 11; Fig.13 is a graph showing the occurrence of autoantibodies directed against the 935-sequence in sera from healthy controls (N=8) and colorectal cancer patients (G1-10, N=10). The full explanation to the Figure is given in Figure 11; Fig.14 illustrates the effect of heat inactivation of albumin neo-structures in healthy (A) and patient (B) sera is demonstrated by analyses of the albumin neo- structure 3028. The effect of heat inactivation of the antibody titres in healthy (C) and cancer patient (D) sera shows release of antibody and a gradual decrease of concentration during dilution. Heat inactivated samples dashed lines and not heat inactivated samples solid lines; Fig.15 is a graph illustrating the occurrence of autoantibodies against peptide 3028 in sera from a cohort of patients with severe infectious diseases. One sample per patient. The titres are significantly reduced in patient sample compared to healthy controls (p=0,000002, T-test); Fig.16 is a graph showing the occurrence of autoantibodies against peptide 3028 in normal plasma, advanced cancer patients, normal sera and a cohort of patients with various infectious diseases; groups of striped and dark bars identify patients with repeated samples also during treatment; Fig.17 is a graph illustrating that patients with necrotizing fasciitis and septic shock showing low antibody titres anti-3028-AMPA which increase during one week of treatment. The same results were obtained for anti.935-AMPA; Fig.18 is a graph showing an analysis of anti-935-AMPA in the second cohort of infectious disease patient sera vs healthy sera, tested by ELISA for anti-935 IgG. Black columns indicate the first and sometimes only sample taken from an infectious disease patient. Black striped columns indicate a second and / or third sample taken from the same patient; Fig.19 illustrates the correlation between titre of AMPA (grey line) directed against the IL-6 inducing albumin neo-structure P935, IL-6IF, and serum concentration of IL-6 (black line); Fig.20 is a graph showing the inhibition of the IL-6 inducing activity of peptide P935 by affinity purified autoantibodies; Fig.21 illustrates the correlation between the serum concentration of autoantibodies / AMPA directed against 935-structures and the serum concentration of IL-6; Fig.22 are images of peripheral blood mononuclear cells (PBMC) showing the inhibition of the binding of anti-CD11a (clone HI111) by incubation of normal PBMCs with cancer patient plasma. Top left image shows CD11a-expressing cells after incubation with plasma from a healthy control and the other images depict cells that were incubated with plasma from 4 different cancer patients, showing a weaker staining; Fig.23 are images of PBMCs showing the restoration of anti-CD18 binding by addition of anti-P3028 antibody or P30. Normal PBMCs were incubated with cancer patient plasma, followed by anti-P3028 antibodies or P30, and staining using the anti- CD18 antibody, MEM48. A. Control, binding of CD18 antibody after incubation with plasma from a healthy individual. B. Inhibition of CD18 antibody binding after incubation with plasma from a cancer patient. C. Incubation with cancer patient plasma followed by anti-P3028 antibodies showing restitution of the binding of the anti-CD18 antibody. D. Incubation with cancer patient plasma followed by incubation with the peptide P30 showing restitution of the binding of the anti-CD18 antibody. The dark cells are strongly stained by the MEM48 antibody; Fig.24. Figure showing the serum factors expressing the 935 structure in sera from patients with infectious diseases are competitively, inhibiting the binding of two biotinylated probes, the 935-peptide and its shorter peptide L10. As shown in the Figure the binding of the probe was significantly inhibited (P<0,01); Fig.25 shows an inhibition ELISA showing a significantly higher concentration of the IL-6 inducing factor in stage IV colon cancer as compared to stage I; Fig.26 shows the serum concentration of the IL-6 inducing albumin neo- structure 935 and its shorter sequence L10 (competitively reduced binding of the probe) according to stage of colon cancer; Fig.27 is a graph which shows the binding of biotinylated anti-integrin antibodies (HI111, 60.3 and MEM48) to AMPA coated ELISA plate compared to the biotinylated probes 935, LEVDET (SEQ ID NO: 4), LEVDETY(SEQ ID NO: 5) and LEVDETYVPK (SEQ ID NO: 6). Results show mean values + / - SEM from duplicate samples; Fig.28 shows Over-all survival, a Kaplan Meier analysis of colon cancer patients, stage III, showing a significantly reduced survival of patients with a high production of the IL-6IF-structure. The discriminatory level was set to 0.7. Logrank test (p=0.0080); Fig.29 contains graphs showing Generation of IL-6 inducing factors by incubation of immunoglobulin G (IvIg) or serum albumin with tumor homogenate; Fig.30 are graphs showing the generation of IL-6 inducing factors by incubation of IvIg or serum albumin with activated MMPs, in particular, MMP-2, -3, -7 and –13 released active fragments from IgG and in particular, MMP- 1, -2, -13 released active fragments from albumin; and Fig.31 shows the inhibition of the binding of the probe 935 to ELISA plates by a factor in sera, IL-6IF, from six patients with colon cancer (A). Addition of antibodies to the sera blocked the inhibitory activity of IL-6IF in five out of six patients. The binding of the probe was thereby significantly increased (B, p<0.05). P935 in the Figure means affinity purified antibodies directed against IL-6IF. Description of embodiments The following description focuses on an embodiment of the present invention applicable for use in diagnostics and the therapeutic treatment of disease. Disease conditions are characterized by a pathogenic, inflammatory activation of the immune system, e.g. IBD, SLE, MS, RA and other so-called chronic inflammatory diseases or autoimmune diseases. In addition, a dysregulated inflammatory activity of major importance for disease development and maintenance is found in cancer, severe infections (e.g. sepsis and septic shock), type 2 diabetes, the metabolic syndrome, neurodegenerative diseases and cardiovascular disease. Interestingly, these inflammatory conditions are generally characterized by an enhanced proteolytic degradation or denaturation of proteins (e.g. ROS), which exposes protein sequences usually hidden in the hydrophobic interior of the proteins, e.g. extracellular matrix (ECM) proteins or possibly also human serum albumin one of the most abundant serum proteins in the body. Thus, in the invention, it is demonstrated that potentially immunoregulatory modified protein neo-structures, such as albumin neo-structure protein fragments, are generated in these inflammatory conditions. This is shown for instance in Example 9. This mechanism / model of regulatory neo-structures is further complicated by their nature being structures never before exposed to the immune system and thereby being immunogenic eliciting an immune response, for example the production of anti- modified-protein-antibodies (AMPA), such as anti-albumin neo-structure protein fragment auto-antibodies. This is shown for instance in Example 6. Thus, in the invention, it was realized that such immunogenicity of modified proteins will result in production of antibodies directed against these structures, Anti Modified Protein Antibodies, AMPA. Anti-modified protein antibodies or AMPAs are antibodies against post- translationally modified proteins and can have the capacity to bind to and block, inhibit or decrease the activity of regulatory modified protein neo-structures. This adds an additional dimension / level of immune regulation by blocking the activity of endogenous, regulatory modified protein neo-structures by the AMPAs. Interleukin-6 (IL-6) inducing protein neo-structures In the search for previously unidentified mechanisms for immunoregulation in cancer, it was found that albumin fragments or denatured albumin had the capacity to induce production of the cytokine interleukin-6 by normal PBMC (peripheral blood mononuclear cell) (US8182983B2), herein expressly incorporated by reference in its entirety. Serum albumin is a multi-functional protein that is able to bind and transport numerous endogenous and exogenous compounds. Also, serum albumin is the most abundant serum protein in the body. Integrins, in particular β2-integrins have been found to be involved in multiple of the immunoregulatory steps of the diseases mentioned above and they have the capacity to bind denatured proteins such as the neo-structures discussed here. Interestingly, denatured human serum albumin structures have been found to bind to the β-chain, CD18, of β2-integrins as demonstrated by competitive binding of monoclonal antibodies directed against CD18 (Davies, 1992). Furthermore, binding of these antibodies to the integrin on immune cells was found to have profound immunoregulatory activity. Thus, it was found that neo-structures from normally occurring proteins potentially have the capacity to play a major immunoregulatory role in a large number of diseases. This is shown in Example 5, Example 9, Further, with the realization that such modified proteins neo-structures will result in production of antibodies directed against these structures (AMPA), it was realized that determination of AMPA can be used in order to describe the production and elimination kinetics of modified proteins and their resulting biological activity. Further, that AMPA could be used as an indirect measure of the biological activity of modified proteins showing inverse correlation with cytokine production and activity of immune cells or with stage and prognosis of the disease under investigation. In addition, methods have been developed to directly measure the immunogenic neostructures. Relevant diseases To fully understand their mode of regulation also the concentration and impact of the corresponding AMPA in addition to the modified protein neo-structures has to be determined. By looking for modified protein neo-structures and their corresponding AMPA specifically in patients with a pathological condition related to or caused by a dysregulated immune system, specific modified protein neo-structures and AMPA can be correlated to the pathological condition. In one example of the invention, such pathological condition related to or caused by a dysregulated immune system include infectious diseases, chronic inflammatory diseases, autoimmune diseases, metabolic syndromes, type 2 diabetes, neurodegenerative diseases, cardiovascular disease or cancer. In one further example of the invention, such cancers related to or caused by a dysregulated immune system include cancer types associated with IL-6, such as Hematological Cancers or Solid Tumor Cancers, such as multiple myeloma, leukemia (such as Acute myeloid leukemia (AML)), Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Lymphoma (such as Hodgkin lymphoma or Non-Hodgkin lymphoma), Breast cancer, Prostate cancer, Lung cancer (such as Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC)), Colorectal cancer, Pancreatic cancer, Ovarian cancer, Liver cancer (Hepatocellular carcinoma), Renal cell carcinoma, Gastric cancer, Bladder cancer, Head and neck cancers (such as Oral cancer, Pharyngeal cancer, Laryngeal cancer), and Sarcomas (such as Osteosarcoma, Ewing sarcoma or Soft tissue sarcoma). The cancers may also be such as colorectal cancer or head and neck cancer. Further, the pathological condition may be an infectious diseases selected from the group consisting of severe infection caused by any microbe, in particular sepsis, septic shock or severe viral infection, such as Covid-19. It was demonstrated that the Immunoregulatory AMPA and modified proteins have the capacity to dysregulate the normal function of the immune system and thereby cause severe symptoms or play a pathogenic role in the pathological condition. Further, the dysregulation of the immune system may be characterized by immune hyperstimulation, e.g. MAS (Macrophage activation syndrome) or cytokine storm, and / or immune suppression of any type. Methods to screen for AMPA correlated to relevant diseases Starting from immune cell binding albumin fragments (US8182983B2) potentially having the capacity to play a major immunoregulatory role the possible occurrence of anti-modified protein antibodies was explored. However, also other neo-structures from normally occurring proteins potentially have the capacity to play a major immunoregulatory role in a large number of diseases. As such, the method may also use other modified protein neo-structures or protein fractions to capture AMPA, and identifying AMPA with a substantially different level in the patients with dysregulated immune system than in healthy controls. High levels of AMPA serves to protect against pathogenic protein neo- structures, a lower level of AMPA would indicate that immune complexes have been formed between AMPA and an excess of the pathogenic neo structures, and thereby neutralizing and eliminating the immune complexes comprising the pathogenic protein neo-structures and the antibodies. In the method, preferably blood plasma or sera from the patient is used, in the analytical the procedure. However, the method is not limited to such samples. Thus, in the invention a method was developed for identifying and characterizing an anti-modified protein antibody associated with a pathological condition related to or caused by a dysregulated immune system. In the method, anti- modified protein antibodies (AMPAs) and their corresponding modified protein neo- structure are identified by preparing chips or peptide array with bound modified protein neo-structure fragments with known amino acid sequences. Blood plasma or sera, from healthy controls or patients with dysregulated immune system, are incubated on said chips to capture Anti-modified protein antibodies (AMPAs) binding to said albumin neo-structure protein fragments. This way, Anti-modified protein antibodies (AMPAs) binding to said peptide arrays, where the level of a captured AMPA is different / altered in patients with dysregulated immune system than in healthy controls, can be identified. Examples of preparation of chips or peptide arrays can be seen in Hansen et al, 2013. Said modified protein may be generated by proteolytic fragmentation or denaturation of normally occurring proteins, such as normal serum albumin. The modified protein may be derived from any protein that after modification bind to cellular receptors, integrins, e.g. human other integrin binding ligand, such as serum albumin, fibrinogen and ECM proteins. The modified protein may be an immune cell surface binding modified protein. The immune cell surface binding modified protein may be derived from human serum albumin. Further, the modified protein may have the capacity to modify cytokine production or the function of immune cells. The body fluid may be selected from or derived from whole blood or fractions thereof, blood plasma, blood serum, lymph fluid, urine, cerebrospinal fluid, saliva, exudates such as ascites or pleural effusions or tissues including biopsies / samples from infectious or inflamed tissues, lymph nodes, tumours including the tissue micro environment. Immune complexes (IC) However, in the invention, it was realized that the simultaneous occurrence of AMPA and protein neo-structures might result in formation of immune complexes (IC), which will have a profound influence on the elimination kinetics of these structures. Formation of IC facilitates the elimination of the albumin neo-structures and the corresponding AMPA. A low AMPA titre can thus be a measure of a high production of albumin neo-structures. Thus, in order to analyse the antigens and antibodies of these immune complexes, the constituents of these immune complexes may have to be released and / or isolated. In fact, if such immune complexes are formed, it is realized in the invention that a true AMPA and protein neo-structure concentration may not be accurately quantified without such a step of first releasing constituents of these immune complexes. Further to properly evaluate the clinical impact, the analyses also have to be performed in a way not changing the amount of free constituents not bound in IC. Thus, the blood plasma or sera may be heat inactivated before the incubation in order to release / separate AMPAs from immune complexes and releasing free / unbound AMPAs into the blood plasma or sera. Heat inactivation for this purpose has been described before, but its effect on release of antibodies was controversial (Cabiedes et al, 1994; Hu et al, 2020). This might depend on the involved antigen and in this investigation, a useful technique was applied. It was found that heat inactivation may use a temperature of between 50 to 70oC, such as 50 to 60oC, and an incubation time of between 5 to 60 minutes, such as 15 to 45 minutes. In one example preliminary experiment, a heat inactivation temperature of 56oC and an incubation time of 30 minutes resulted in separate AMPAs from immune complexes (IC). Determination of modified proteins by inhibition ELISA These modified proteins may be determined by inhibition ELISA: ELISA plates coated with AMPA will bind the tagged (e.g. with biotin) specific modified proteins. Addition of plasma / sera containing the same neo-structure will compete with of the tagged modified protein resulting in reduced binding, which constitutes a measure of the amount of that specific modified protein in plasma / sera. Methods correlating albumin neo-structures and corresponding anti-albumin neo-structure antibodies with a pathological condition The methods may thus identify, quantify and correlate modified protein, and corresponding modified protein antibodies associated with a pathological condition related to or caused by a dysregulated immune system. The clinical impact / the pathogenic role of albumin neo-structures or the corresponding AMPA is demonstrate by their correlation to the stage of the disease, the prognosis of the disease, dysregulation of the immune system or changes related to standard treatment The impact of binding immunoregulatory modified proteins to immune cells is described in Examples 1-3. AMPA and Monoclonal antibodies Thus, using the methods described herein one can characterize an antibody which specifically binds to a modified protein neo-structure associated with a pathological condition related to or caused by a dysregulated immune system. The antibody blocks, inhibits, eliminates or decreases the immunoregulatory activity of said modified protein neo-structure. The antibody may also be a monoclonal antibody, recombinant monoclonal antibody or a recombinant polyclonal antibodies. Thus, one may make a monoclonal antibody, wherein the monoclonal antibody is an anti-modified protein human or humanized monoclonal antibody which blocks, inhibits, eliminates or decreases the activity of an immunoregulatory anti-modified protein in in a subject. The immunoregulatory modified protein may be an immune cell surface binding modified protein. The immunoregulatory anti-modified protein may be derived from human serum albumin can modify cytokine production or immune cell function. The immunoregulatory anti-modified protein may be derived from human serum albumin and may induce production of interleukin-6 by normal immune cells. Thus, one may make a pharmaceutical composition comprising such an anti- modified protein antibody. The pharmaceutical composition may also comprise a pharmaceutically acceptable carrier, excipient or stabilizer. Examples of stabilizers are sucrose, trehalose, mannitol, sorbitol and arginine hydrochloride. Similarly, excipients may be a bulking agent, salt, surfactant and preservative. The pharmaceutical composition may also comprise a buffer system, to provide a formulation with a pH from 3 to 9, preferably a pH from 5.5 to 7.5. A buffer system may be selected from a group consisting of citrate, histidine, sodium succinate, and sodium and / or potassium phosphate or carbonate buffer system. The composition is preferably suitable for intra-venous or subcutaneous administration. The occurrence of AMPA and the corresponding B-cells enables the production of human monoclonal antibodies using the single B-cell technique. The sequencing of AMPA enables the identification of CDR sequences and enables the identification of CDR sequences and production of monoclonal or polyclonal recombinant antibodies. These antibodies will be used for diagnostic and therapeutic purposes in order to improve the care of patients with this type of dysregulated of immune system. Diagnostic use Having correlated a modified protein, e.g. modified albumin and the corresponding anti-modified protein antibody, e.g. anti-albumin antibody to a specific condition, the AMPA may be used as an indirect measure of the amount or the biological activity of modified protein. Thus, the antibodies (AMPAs) may show an inverse correlation with cytokine production, function of immune cells or with stage and prognosis of the disease under investigation. The diagnostic tests based on removal of immunoregulatory modified proteins from immune cells by incubation with AMPA is described in Examples 1-3. As described in Example 3, immunoregulatory modified protein neo-structures may bind to immune cell surface receptors modulates the function of these cell, such as their production of cytokines or expression of cell surface receptors / markers, resulting in dysregulation of the normal function of the immune system. In the invention, it is realized that the removal of these neo-structures from their cell receptors will therefore result in normalization of the function of the immune system. Further, that removal can be achieved by incubation with AMPA. In a method of the invention, immune cells from patients with pathological conditions are isolated. The cells are divided into two cell portions, wherein the first is incubated with AMPA in order to remove cell bound modified protein neo-structures. The cell portions are then cultured in the in a medium for at least one day, and the production of cytokines in the culture supernatants is determined. In an alternative method, cells from such cultures may be harvested and the expression of cell surface markers before and after AMPA incubation is determined using Flow Cytometry. These analyses can be performed either using specific / epitope specific AMPA (affinity purified using the specific peptide or epitope) or total AMPA including all released antibodies in the serum. Using specific / epitope specific AMPA, the immune parameter related to only one neo-structure will be analyzed. Using total AMPA will disclosed the total dysregulation by immunogenic immunoregulatory neo-structures in that particular patient. Using this method, removing cell bound neo-structures with AMPA will create valuable diagnostic information on which therapeutic strategies can be based. Thus, a pathological condition related to or caused by inflammation or a dysregulated immune system may be diagnosed using the methodology above, Immune parameters related to a modified protein neo-structure may be identified and characterized by, in an isolated sample of immune cells from a patient with a pathological condition, determining which modified protein neo-structures are involved in immunoregulation. The technique with total AMPA is of particular interest as dysregulation of the immune system often is multi-factorial. Based on which a correct selection of neo- structures to be therapeutically removed / inhibited / blocked, a panel of dysregulatory neo-structures and AMAP can be identified. In this context, the recently developed technique to produce recombinant polyclonal antibodies can be useful (Rapid Novor). Thus, the antibodies of the invention may be recombinant polyclonal antibodies. Therapeutic use Monoclonal antibodies made from AMPA may be used for therapeutic inhibition of the regulatory function or elimination of said modified proteins in order to ameliorate the symptoms of or in order to cure that particular disease (pathological condition related to or caused by a dysregulated immune system). Therapeutic inhibition of the regulatory function of said modified proteins can include: • Blockade / inhibition / of the modified proteins by binding of monoclonal or recombinant polyclonal antibodies or synthetic molecules to any part of this structure. • Removal of relevant modified proteins by administration of monoclonal or recombinant polyclonal antibodies or synthetic molecules directed to a different or any epitope of the modified proteins. • Modulation of the binding of modified proteins to its target by administration of proper modulators of this target molecule. • Administration of substances which suppress / inactivate / neutralize the activity of the modified proteins or make it redundant. • Changing the balance between inhibitory and stimulatory modified proteins. • Modulate the balance / ratio of specific immune complexes. Thus, a pathological condition related to or caused by a dysregulated immune system can be verified or diagnosed using a method of the invention. In a sample from a patient, such as a body fluid like plasma or serum, anti-modified protein antibodies (AMPAs) or modified proteins that have been linked to a specific pathological condition using the method of the invention, may be identified and determined. The presence of such an anti-modified protein antibody (AMPA) or modified protein is linked to a specific pathological condition, may thus be used to verify that the patient suffers from said pathological condition. Similarly, an immune response can be stimulated or a pathological immune response can be inhibited in a subject, by administering an antibody (linked to a specific pathological condition using the method of the invention) or a pharmaceutical composition comprising said antibody, in an amount effective to stimulate or inhibit the immune response. Further, an inflammatory response can be modulated in a subject, by administering to the subject an effective amount of an antibody (linked to a specific pathological condition using the method of the invention), wherein the antibody is a human or humanized monoclonal or recombinant polyclonal antibodies which blocks, inhibits, eliminates or decreases the activity of an immunoregulatory modified protein neo-structure in the subject. Therefore, a pathological condition related to or caused by a dysregulated immune system may be treated by administering to a subject in need thereof an isolated antibody molecule (linked to a specific pathological condition using the method of the invention) in an amount effective to treat the a pathological condition related to or caused by a dysregulated immune system. The pathological condition related to or caused by a dysregulated immune system may be an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or cancer. The pathological condition may be an infectious diseases selected from the group consisting of severe infection caused by any microbe, in particular sepsis, septic shock or severe viral infection, such as Covid-19. The antibody may specifically bind to an immunoregulatory albumin neo- structure. Thus, a disease may be treated by blocking, inhibiting, eliminating or decreasing the activity of an immunoregulatory modified protein neo-structure in a subject, and this may be accomplished by administering to the subject an effective amount of a monoclonal or a recombinanat polyclonal anti-albumin neo-structure antibody (linked to a specific pathological condition using the method of the invention). MATERIAL AND METHODS Preparation of peripheral blood mononuclear cells (PBMC) Isolation of peripheral blood mononuclear cells (PBMC) Venous blood was drawn from healthy volunteers or from cancer patients in glass vaccum tubes with acid dextrose citrate solution A as anti-coagulant (Vacutainer, Becton Dickinson, Franklin Lakes, NJ). Erythrocytes were removed by sedimentation on 2% dextran T500 solution (Amersham Pharmacia Biotech AB, Uppsala, Sweden) in 0.9% NaCI. PBMC were then isolated by Ficoll- paque Plus (GE Healthcare Bio-Sciences AB, Uppsala, Sweden) density gradient centrifugation after which the cells were washed twice in RPMI 1640 Dutch's modification (Gibco, InVitrogen AB, Stockholm, Sweden) with 2% human serum albumin (HSA) 5 (Pharmacia & Upjohn, Stockholm, Sweden) (RPMI / 2%HSA). Cell viability was assessed by exclusion of 0.05% Trypan Blue and was always above 95%. The cell suspension was stained with Turk's solution and the number of lymphocytes and monocytes in the PBMC preparation were 10 counted in a hemocytometer. PBMCs were suspended in RPMI / 2%HSA and the cell concentration adjusted to 5 x 105lymphocytes / ml. Preparation of serum samples Human serum was collected in serum collection tubes without additives (Vacutainer, Becton Dickinson, Franklin Lakes, NJ) at the same time as blood samples for isolation of PBMC. Sera, collected from cancer patients or from normal healthy individuals, were heat-inactivated for 30 minutes at 56oC and frozen at -70oC. After thawing, sera were diluted in RPMI1640 to a concentration of 20% and either used unfiltered or ultra-filtered, as described below, in co-culture experiments for monokine-induction with control PBMC. 100 μl of diluted sera (20%) or ultra filtered serum fractions were added to uncoated or HSA-coated microtiter plates together with 100 μl PBMC suspension (5 x 105 / ml). Cell-free SNs were harvested after over-night incubation and tested for monokine activity by ELISA, as described above. Ultra filtration All ultra filtrations were carried out using Amicon Centriplus centrifugal filter devices (Millipore Co. MA, US) sterilised by autoclave. Filters with a 3000, 50000, or 100000 molecular weight cut-off were used. The Centriplus filters were washed with RPMI1640 prior to use. The Centriplus filters were spun on a refrigerated centrifuge with a swing- out rotor at 3000 x g. Retentates were recovered by inverse centrifugation at 2000 x g. Ultra filtered serum fractions consisted of filtrates from 100000 mw cut-off filters, retentates or filtrates from 50000 mw cut-off filters or retentates from serum fractions that had been sequentially spun on a 50000 mw cut-off filter followed by concentration on a 3000 mw cut-off filter. Retentates were reconstituted in RPMI1640 with 200 IU / ml penicillin, 200 μg / ml streptomycin, 4 mM L-glutamine (Sigma) to their original volume. Preparation of urine samples Approximately 15 ml of urine were collected from cancer patients with renal cell carcinoma or malignant melanoma or from normal healthy individuals. The samples were centrifuged for 10 minutes at 3000 x g followed by filtration over a 0.45 μm Millex-HV syringe filter (Millipore). Next the samples were ultra filtered through a 50000 mw cut- off Centriplus filter and the filtrate concentrated on a 3000 mw cut-off filter. The volume of the retentate, collected from the 3000 mw filter was adjusted to 1 ml with RPMI1640. The sample was then again filtered on a 0.45 μm Millex-HV syringe filter and frozen at - 70oC. Immediately before co-culture with normal PBMC, the samples were thawed and buffer exchange was performed to RPMI1640 with 200 IU / ml penicillin, 200 μg / ml streptomycin, 4 mM L-glutamine (Sigma) by gel filtration over a Sephadex-G25 (PD-10) desalting column (Pharmacia, SE). Albumin peptides Synthetic albumin peptides used herein were custom prepared by Schafer-N (Copenhagen, Denmark) CSBio Co, Menlo Park, CA. Peptides were > 95% pure as confirmed by HPLC. Peptides were kept freeze dried at minus 2O0C. Peptides were reconstituted in sterile H2O (Sigma) for use in ELISA or in RPM11640 (GIBCO) for use in cell culture experiments. Peptides were sterile filtered through a 0.22 μm syringe filter (Millipore Co) before use in cell culture experiments. Preparation of denatured Human Serum Albumin (dHSA) Human serum albumin (HSA) infusion solution (Pharmacia, Uppsala, Sweden) was denatured and reduced by resuspending it at a final concentration of 10 mg / ml in 8 M urea and 10 mM dithiothretiol (both from Sigma Chemical Co, St. Louis, MO) in 50 mM Tris-HCL (pH 7.9) for 2 h at 250C. The HSA was then alkylated by the addition of 60 mM iodoacetamide (Sigma) and further incubated for 2 h at 250C in the dark. The HSA solution was diluted to a concentration of 100 ug / ml with phosphate buffered saline (PBS, Gibco BRL) and dialyzed extensively against PBS using Spectrapore 4 dialysis tubing with a cut-off of mw 12000 (Spectrum Europe, Breda, The Netherlands). Control HSA was prepared in parallel by incubating HSA at 10 mg / m in Tris-HCL (pH 7.9) followed by dialysis. Before use in tissue culture experiments the dHSA was sterile filtered through a 0.22 Dm syringe filter (Millipore Co, MA, USA). DHSA was either stored at 40C or freeze dried and stored at -2O0C. Culture of PBMC Pre-coating of culture plates with HSA and HSA / IgG Round-bottomed, 96-well tissue culture plates (Costar, Corning Inc. NY, US) were pre- coated with HSA only or HSA and pooled human IgG for intravenous injection (Gammagard, Baxter AS, DK). HSA was diluted in RPMI1640 without supplements to a concentration of 10 mg / ml. In some experiments, 1 mg / ml IgG was mixed into a solution of 9 mg / ml HSA in RPMI (HSA / IgG). 200 μl of HSA or HSA / IgG were then added to each well of the plate. The plates were incubated at 4oC for 30 minutes after which the wells were washed twice with 200 μl of RPMI1640. The coated plates were used immediately. Generation of cell culture supernatants for monokine determination 100 μl of culture medium consisting of RPMI1640 supplemented with 200 IU / ml penicillin, 200 μg / ml streptomycin, 4 mM L-glutamine (Sigma Chemical, MO, US) and 20% fresh heat-inactivated autologous serum were added to un-coated or -pre-coated microtiter plates followed by 100 μl of PBMC suspension (5 x 104lymphocytes) in RPMI / 2%HSA. In some experiments Lipoplysaccharide (LPS, Sigma Chemical Co, MO, US) was added at a concentration of 0.05 ng / ml. Cells were cultured in a humidified, 5% CO2atmosphere at 37oC. Supernatants (SNs) were harvested after 24 hrs and residual cells were removed by centrifugation in a refrigerated centrifuge (Beckman) at 2600 x g for 5 minutes. SNs were frozen and stored at -70oC until monokine concentrations were measured by ELISA. Monokine ELISA Monokines were assessed by ELISA using the DuoSet ELISA development system for human IL-6, TNF-α or IL-1β (R&D Systems Europe Ltd., Abingdon, UK) following the manufacturer's recommended procedures. Lower limit of detection was 3.1 pg / ml for IL- 6, 15.6 pg / ml for TNF-α and 3.9 pg / ml for IL-1β. IL-10 was detected with a kit from Diaclone Research, FR. The lower limit of detection was 5 pg / ml. Human IL-1Ra was detected with a quantitative sandwich ELISA using a monoclonal mouse anti-human IL- 1Ra as capture antibody and a biotinylated goat anti-human IL-1Ra as developing antibody (both from R&D Systems). Briefly, enhanced binding 96-well microtiter plates (Labsystems AB, SE) were coated overnight at room temperature with 10 μg / ml of capture antibody diluted in PBS. After washing in PBS with 0.05% Tween 20 (Sigma Chemical, MO, US) plates were blocked with a blocking buffer consisting of 1% bovine serum albumin (BSA, Sigma), 5% sucrose (Sigma) and 0.05% NaN3in PBS. PBMC culture SNs or recombinant human IL-1Ra standard (R&D Systems) were diluted in 0.1% BSA and 0.01% Tween 20 in PBS (dilution buffer) and incubated over night at room temperature. After washing, the biotinylated-developing antibody was added at 100 ng / ml in dilution buffer. This was incubated for 1 hr at room temperature. Plates were washed and alkaline phosphatase (ALP)-conjugated Extravedin (Sigma), at a dilution of 1:10000 in Tris buffered saline with 0.1% BSA was added. Following incubation for 1 hr at room temperature, plates were washed and the amount of bound IL-1Ra was measured by hydrolysis of paranitrophenyl phosphate (Sigma). Optical density was read at dual wavelengths, 405 nm and 570 nm, respectively, in a Multiscan EX microplate reader (Labsystems). The lower limit of detection in this assay was 39 pg IL-1Ra / ml. Samples were analysed as mean of triplicate wells. Autoantibody ELISA This protocol describes the detection method for assaying relative amounts of total autoantibodies that bind 3028-structures, which are present in human plasma. Heat- inactivation allows greater release of autoantibodies from immuno-protein aggregates present in plasma, thereby enabling a more complete detection of relevant 3028- autoantibodies. For ELISA Coating, a Maxisorp 96 well plate (Nunc; #442404) was coated with a solution of 1x Phosphate Buffered Saline (PBS) pH 7.4 containing 5 ug / ml Peptide-3028, 100 ul per well. The plate was incubated overnight at 4°C. The next day, healthy and infectious disease sera (and comparison plasmas) were defrosted at 37°C for 30 minutes, then diluted to 2% in a solution of PBS containing 1% fish gelatin (Sigma; #G7041) as a buffering and blocking agent (FG-PBS). The 2% diluted samples were heated at 56°C for 30 minutes. The ELISA plate was washed 3x with PBST and 200 ul per well of FG-PBS was added for blocking, with a 60 minute incubation at room temperature. Following blocking, the plate was washed 3x with PBST and 100 ul per well of 2% diluted sera (or plasma) was added to relevant wells. The plate was incubated for 2 hours at room temperature. Following 3x washes with PBST, the detection antibody was added at 100 ul per well. This was an HRP-conjugated sheep-anti-human-IgG antibody (GE; #NA933) diluted 1 / 3000 in FG-PBS. The plate was incubated for 60 minutes at room temperature and then washed 5x with PBST over 10 minutes. The TMB developer solution (Sigma; #T4444) was added to the wells (100 ul) and the plate was incubated for 30 minutes at room temperature in darkness. The development was stopped with 100 ul per well of 1 molar sulfuric acid. The developed plate was placed in a FluoStar Omega plate spectrophotometer (BMG LabTech) and absorbance readings were taken at 450nm and 570nm. The resulting data was converted to a Microsoft Excel file, where the values were averaged and graphed. Affinity chromatography of human sera with protein G-coupled Sepharose Heat-inactivated human serum was passed over a HiTrap protein G-Sepharose HP affinity column (Amersham Pharmacia Biotech AB, SE). The non-binding fraction was eluted with RPMI1640, giving a final dilution effect of 1 / 5 (20%) of the original serum. 200 IU / ml penicillin, 200 μg / ml streptomycin, 4 mM L-glutamine (all from Sigma) were added. The eluate was then sterile filtered with a 0.45 μm Millex syringe filter (Millipore Co. MA, US) and used immediately for culture with control PBMC.100 μl medium with 20% original serum or with 20% protein G non-binding serum from the same source was added to uncoated or HSA-coated microtiter plates together with 100 μl PBMC suspension (5 x 105 / ml). Cell-free SNs were harvested after over-night incubation and tested for monokine activity by ELISA, as described above. Sample preparation for 2-D gel electrophoresis Urine samples (100 – 450 ml) from cancer patients or healthy controls were ultra centrifuged on Jumbosep centrifugal devices (Pall Life Science, MI, US) using a 30 K membrane insert or alternatively, with a Proflux M12 system using a 30 K Pellicon 2 mini filter (Millipore, MA, US) followed by concentration on Jumbosep with a 3K membrane insert. The urine fraction, 3-30 KD, was tested for monokine-inducing activity as previously described herein. Protein concentrations were determined by Bio-Rad protein assay (Bio-Rad Laboratories, CA, US). Samples were desalted over a Sephadex-G25 (PD-10) column (Amersham Biosciences, SE), lyophilised and dissolved in rehydration buffer (8M urea, 4% CHAPS, 10mM DTT, 0.5% v / v IPG buffer and a trace of orange G). Samples were centrifuged to remove undissolved material. PBMC-adsorbed urine fractions from cancer patients PBMC were prepared from buffy coat peripheral blood from normal controls as described above. Monokine production by the PBMCs in response to urine fractions from cancer patients was verified as described above. Remaining PBMC were frozen at –70oC until use. For adsorption of urine fractions, the PBMCs were thawed and washed carefully in cold phosphate buffered saline (PBS). Approximately 50 x 106PBMC were added to 2.7 or 2.6 ml, respectively, of ultra centrifuged (3-30 KD) urine fractions pooled from two patients with renal cell carcinoma or from one patient with malignant melanoma. Unabsorbed urine fractions, used as controls, received the equivalent volume of PBS without PBMC. The urine fractions were incubated for 1½ hour at 4oC. The PBMC were then removed by centrifugation. The adsorbed urine fractions were tested for monokine- inducing activity in fresh, normal PBMC as described above. Remaining urine fractions were stored at –70oC until determination of protein concentration and analysis with 2-D gel electrophoresis, mass spectrometry and N-terminal sequencing. 2-D gel electrophoresis and Mass spectrometry 2-D was performed in a horizontal 2-D set-up (Multiphore / IPGphore, Pharmacia Biotech, SE) as described (Lindahl M. et.al 1998) based on isoelectric focusing (IEF) in the first dimension and molecular mass in the second dimension. Briefly, samples (230µg, 350µg, 600µg) were applied to IPG gels, pH 4-7, (Amersham Pharmacia Biotech, SE) and focused overnight for 48000Vh. SDS-PAGE was then carried out with 16% T / 1% C polyacrylamide casted slab gels. Molecular weight standards were included in each run. Separated proteins were detected by Coomassie blue staining or SYPRO Ruby staining. The protein patterns in the gels were analyzed as digitised images using a CCD (Charged-Coupled Device) camera (1340 x 1040 pixels) in combination with a computerized imaging 12-bit system, PDQuest Version 6.1.0, in the case of fluorescent stained gels using UV scanning illumination mode (Fluor-S Multi- imager, Bio-Rad). The amount of protein in a spot was assessed as background- corrected optical density, integrated over all pixels in the spot and expressed as integrated optical density (IOD). Tryptic digests of excised protein spots were performed using MALDI_TOF MS (Voyager-DE PRO, Applied Biosystems, CA, US) as previously described (Ghafouri B. et al.2002) Electrotransfer and N-terminal sequence analysis Selected protein spots were electro transferred to PVDF membranes and subjected to N- terminal sequence analysis by Edman degradation in a Procise cLC or a Procise HT sequencer (PE-Applied Biosystems) at the Protein Analysis Center, Karolinska Institute, Stockholm, Sweden. Proteolytic fragmentation of IgG and serum albumin Fragmentation of IgG and serum albumin using matrix metalloproteinases (MMPs) MMP -1, -2, –13 (R&D Systems) and MMP-3 and -7 (Chemicon, UK) were activated according to instructions of the manufacturer.1-50 ng / ml of the indicated MMPs were then incubated with 1 mg / ml of either human serum albumin (HSA, Octapharma, SE) or pooled human IgG for intravenous injection (IvIg, Gammagard, Baxter, DK) as substrate in RPMI or in 50 mM Tris-HCl, pH 7.5 (containing 0.15 M NaCl, 10 mM CaCl2 and 0.05% Brij35). The mixtures were incubated for 5-20 hours at 37°C. Parallel incubations of MMP or the substrates alone, in respective buffer, were set up as controls. The mixtures were buffer exchanged to RPMI as described previously and filtered through a 0.45 μm Millex-HV syringe filter (Millipore, MA, US). Storing of mixtures, when needed, was performed at -70°C until testing for monokine inducing activity in fresh, normal PBMC as described above. Fragmentation of IgG and serum albumin using homogenized tumour biopsies Frozen, human tumour biopsies, embedded in Tissue-Tek OCT Compound (Sakura, NL) or cryostat sections from patients with renal cell carcinoma, malignant melanoma or colon carcinoma were transferred to 3-10 ml of cold RPMI or PBS with 200IU / ml penicillin and 200 μg / ml streptomycin (RPMI / PEST, PBS / PEST) (Gibco BRL) and kept on ice. The tissue was washed three times by centrifugation and resuspension in 3- 10 ml cold RPMI / PEST or PBS / PEST. The pelleted, washed tissue was cut into pieces of approximately the same size and each piece was homogenised using a Mikro- Dismembrator U (B. Braun Biotech International, GE). The tissue was transferred to a PTFE shaking flask together with 1 ml RPMI / PEST or PBS / PEST and a tungsten carbide grinding ball and homogenised during 15-20 seconds with a shaking frequency of 1500-2000 RPM. The homogenised tissue suspension was transferred to a test tube and kept on ice or stored at -70°C. The homogenised sections were then washed once more to collect a fourth supernatant, used as a control reflecting the IL-6 inducing activity in tumour sections before incubation. The fourth supernatant was divided into two parts, to one of which was added 20 mg / ml of HSA and directly frozen at -70°C. The mixtures of homogenised tumour tissue with 20 mg / ml HSA or with 10 mg / ml pooled human IgG all in RPMI / PEST, were incubated for 18-21.5 h at 37°C. Parallel incubations of tumour tissue and PIF with no addition of HSA or IvIg, as well as RPMI / PEST with addition of HSA or IvIg, were set up as controls. The mixtures were centrifuged and supernatants collected. The supernatants were buffer exchanged to RPMI as described previously and filtered through a 0.45 μm Millex-HV syringe filter (Millipore, MA, US) and stored at -70°C until testing for monokine inducing activity in fresh, normal PBMC as described above. Identification of immune cell binding albumin sequences -- Artificial cell surface chromatography Preparation of cell lysate from PBMC with biotinylated cell surface proteins (ACS) Buffy coats generated from 450 ml blood each was collected from 4 healthy donors. Erythrocytes were removed by sedimentation on 2% dextran T500 solution (Amersham Pharmacia Biotech AB, Uppsala Sweden) in 0,9% NaCI. Mononuclear cells (PBMC) were then isolated by Ficoll-Paque Plus (GE Healthcare Bioscience AB Sweden) density gradient centrifugation. The PBMC were then suspended in phosphate buffered saline (PBS) containing Ca and Mg (GIBCO) at a concentration of 10 x 106 / ml. EZ Link Sulfo- NHS-biotin (Pierce USA) was added at a final concentration of 0.2 mg / ml and the mixture inkubated on a shaker at room temperature for 10 min. Excess biotin was then removed by washing the PBMC in PBS. Biotinylated PBMC were then lysed by adding 1 ,0 ml ice-cold lysing buffer (50 mM Tris-HCL, pH 7.5, with 0.15 M NaCI, 5 mM MgCI2 containing 100 mM Octyl glucoside and 1 mM Phenylmethylsulfonyl fluoride) per 2 x 107pelleted cells with gentle shaking, then incubated for 30 min. on ice. Debris was removed by centrifugation at 5000 x g at 40C for 10 min and the supematants was collected and pooled from all four donors. The lysate was then stored at -700C in polypropylene plastic tubes. Preparation of affinity column with biotinylated cell surface proteins from mononuclear cells coupled to streptavidin-Sepharose. 18 ml biotinylated cell lysate in lysate buffer was diluted 1 / 10 in binding buffer (20 mM NaH2PO4, 0,15 M NaCI, pH 7.5). This amount of lysate corresponds to 36 x 107mononuclear cells. It was added to a 1 ml Hitrap Streptavidin HP affinity column (Amersham Biosciences). To block possible remaining free biotin, 5 ml of 0.1 M glycine (Sigma) was added to the column. Unsaturated streptavidin on the column was then reacted with 150 ug biotin (Sigma) in binding buffer. The column was carefully washed with PBS and stored in PBS with 0,1% NaN3 at 4°C until use. Proteolytic fragmentation of denatured human serum albumin with trypsin. Freeze dried HSA (0.5mg) was reconstituted in 25 mM NH4HCO3, pH 8, containing 10mg sequencing grade modified trypsin (Promega Corporation, WI) and incubated at 37oCovernight. To remove unfragmented albumin and enzyme the sample was ultrafiltered through an Amicon Ultra 4 (MW cut-off of 5000) or a Centriplus (MW cut-off 10000) centrifugal filter (Millipore AB, Solna, Sweden). The filtrate, containing fragmented HSA without enzyme was collected and diluted with PBS with Ca and Mg (GIBCO). Adsorption of trypsin-fragmented dHSA using an affinity column with biotinylated cell surface proteins (ACS) Two ml of trypsin-fragmented dHSA in PBS, corresponding to a total of 0.2 mg protein, was passaged over the ACS column, prepared as described above. The flow-through was collected with consideration taken to void volume and dilution of adsorbed sample by collecting in small portions of 0.2 ml. Thirty ul of each sample, including a control sample that has not been adsorbed, were dried in a Speed-Vac centrifuge. Mass spectrometry Dried samples were reconstituted in 10 ul of 0.1 % TFA. Zip Tip pipette tips (Millipore, USA) containing C18reversed-phase media were used for desalting reconstituted samples. For analysis of samples in the mass range 700 - 3600 Da, one μl of each Zip Tip eluted sample was mixed with 1μl of a saturated solution of α-cyano-4-hydroxycinamic acid (0.02mg / ml) in 70%acetonitrile / 0.3% trifluoro acetic acid. For the analysis of samples in the mass range 1500 - 9000 Da, one μl of each Zip Tip eluted sample was mixed with 1 μl of sinapinic acid (3-methoxy-4-hydroxycinnamic acid). 1 μl of the mixture was spotted on the MALDI plate and analysed using MALDI-TOF MS (Voyager- DE PRO, Applied Biosystems, CA, US). Mass identity search of resulting spectra was performed in the SwissProt or NCBI databases using MS-Fit. Generation of rabbit antiserum specific for albumin peptide 3028 and peptide 935 Peptide 3028 and peptide 935 were synthesized with a cysteine added to the N-terminus end and then conjugated with keyhole limpet hemocyanin (KLH) as a carrier protein. Polyclonal antisera were generated by repeated immunizations of rabbits with KLH- conjugated peptides and Freund's adjuvants. Rabbit antibodies were prepared using affinity chromatography over protein-A Sepharose and the specific antibodies were prepared by affinity chromatography using columns with bound 3028 peptide or 935 peptide (Ultralink lodoacetyl gels (Pierce Biotechnology Inc.). For cell culture experiments, buffer exchange to RPMI 1640 Dutch's modification (Gibco, InVitrogen AB, Stockholm, Sweden) was performed by passage over PD-10 sephadex columns (Amersham Biosciences, Uppsala, Sweden) followed by filter sterilization on 0.22 μm Millex syringe filters (Millipore Co., MA, USA). Rabbit immunizations and purification of antisera were carried out by Agrisera AB, Sweden. IHC using anti-3028 and 935 rabbit antibodies. Frozen tissue sections were fixed in fresh ice cold acetone for 5 min. and dried at room temperature. The slides were hydrated in TBS for 2 min with added protease inhibitor and washed in TBS for 5 min (x 3), incubated with primary antibody in 2.5 % ready to use horse serum with added protease inhibitor (150 µl / slide) for 1h at room temperature, washed in TBS for 5 min (x 3). Rabbit specific AP conjugate 150 µl / slide was applied and incubated for 30 minutes at room temperature, washed with TBS for 5min (x 4). Then 10 drops of Levamisole were added to 80 μL Immpact Vector Red reagent 1 and 60 μL reagent 2 per 5 mL and 150 µl / slide was applied onto the slides, incubate for 5 minutes at room temperature, washed in TBS (x 4) followed by Millipore water before counter- staining with Haematoxylin for 8 min. and mounted with CYTOSEAL XYL. The specificity of the staining using oligoclonal rabbit antibodies directed against P935 or P3028 was demonstrated as the binding of the antibodies to tumours was generally completely inhibited by preincubation of the antibodies with P935. In some tumours a strong staining of a few cells with macrophage morphology was observed also after peptide blockade of the antibodies. This background staining was very limited and did never interfere with the evaluation of the staining pattern. Statistical Analysis Comparisons of the means of different patient groups or different test occasions were performed using an unpaired t-test. Time to progression and survival was analyzed using the Kaplan-Meier method and Logrank test. Examples Identification / Discovery of immunoregulatory albumin neo-structures. Dysregulation of the immune system, either over-reactivity or down-regulation of the activity (immunosuppression) is of major importance in the pathogenesis of a large number of diseases. The detailed mechanisms involved are still poorly understood. However, the cytokine interleukin-6 (IL-6) is a key player in pathological regulation in multiple conditions such as chronic inflammation, autoimmune diseases, metabolic syndrome, cancer. cardiovascular diseases and neurodegenerative diseases. Previously unknown IL-6 inducing factors were found in cancer patient sera and urine. Such factors in urine, adsorbed by mononuclear blood cells, were found to be serum albumin fragments. Further, proteolytic fragmentation of albumin by tumour homogenates or MMPs generated IL-6 inducing neo-structures / fragments. Immune cell binding of albumin fragments was identified using Artificial Cell Surface Chromatography, that is albumin fragments obtained by standard trypsination were adsorbed by selectively biotinylated cell surface structures bound to streptavidin beads. Binding peptides, identified using MALDI-TOF-MS, were synthesized and tested in PBMC cultures. Interestingly, this technique also discovered an albumin fragment, P3028, involved in immunosuppression in cancer. Therefore, primarily resources were focused on characterization of this fragment, which was found to bind to the β2-integrin LFA-1, inhibit lymphocyte proliferation and migration and NK-cell cytotoxicity (Patent No WO2008 / 136736). Summary of results In the invention presented here, immunoregulatory albumin neo-structures, such as the IL-6 inducing factor, were characterized. The role of immunoregulatory, pathogenic albumin neo-structures are described. Further, this application presents autoantibodies, Anti-Modified-Protein.Antibodes (AMPA) against such neo-structures. The capacity of antibodies with these particular specificities, to inhibit the pathogenic activity of albumin neo-structures was clarified. Based on these discoveries therapeutic recombinant poly- or monoclonal antibodies can be produced. The specificity of such antibodies can be very specific, directed against only one neo-structure or broad, directed against multiple neo-structures useful in multifactorial dysregulation of the immune system. Therapeutic antibodies can also be directed against albumin or albumin fragments exposing pathogenic neo-structures. Using this therapeutic strategy, selectively pathologic IL-6 production (due to an enhanced proteolytic degradation or denaturation of proteins) can be inhibited leaving the normal, physiologic production intact enabling the normal function of the immune system in the control of non-self. The following experiments and examples have been made or planned: Example 1 -- Identification of an IL-6 inducing neo-structure. A fragment of human serum albumin. In the present investigation one of the albumin fragments, P935, binding to cell surface receptors / structures in Artificial Cell Surface Chromatography was found to induce IL- 6 synthesis when incubated with PBMC from healthy donors. This is seen in Fig.1, which shows the production of IL-6 in short term cultures of PBMC from healthy individuals after addition of P935 (29935) peptide. An artificial cell surface (ACS) was prepared as described, and a mixture of peptides obtained after trypsination was adsorbed by ACS and the binding peptides were identified by comparing adsorbed and unadsorbed peptide solutions using the MALDI TOF ms technique. These peptides are shown in the table below (WO2008136736): Table 1. Immune cell binding albumin peptides. % Seq Start-enSEQ ID NO absd0,71 (K)KYLYEIAR (R) 161-168 Seq ID No 7 0,64 (K)KVPQVSTPTLVEVSR (N) 438-452 Seq ID No 8 0,60 (K)VFDEFKPLVEEPQNLIK (Q) 397-413 Seq ID No 9 0,59 (K)VPQVSTPTLVEVSR (N) 439-452 Seq ID No 10 0,42 (R)RPCFSALEVDETYVPK (E) 509-524 Seq ID No 11 0,41 (K)FQNALLVR (Y) 427-434 Seq ID No 12 0,36 (K)SLHTLFGDK (L) 89-97 Seq ID No 13 0,36 (K)LKECCEKPLLEK (S) 299-310 Seq ID No 14 0,35 (K)LCTVATLR (E) 98-105 Seq ID No 15 0,34 (K)YLYEIAR (R) 162-168 Seq ID No 165 0,32 (K)CCAAADPHECYAK (V) 384-396 Seq ID No 17 0,29 (K)AAFTECCQAADK (A) 187198 Seq ID No 18 0,26 (K)CCTESLVNR (R) 500-508 Seq ID No 19 0,26 (K)QEPERNECFLQHK (D) 118-130 Seq ID No 2100 0,23 (K)AVMDDFAAFVEK (C) 570-581 Seq ID No 21 0,22 (R)NECFLQHK (D) 123-130 Seq ID No 22 0,20 (K)QNCELFEQLGEYK (F) 414-426 Seq ID No 23 15 0,18 (K)QEPERNECFLQHK (D) 118-130 Seq ID No 24 0,13 (K)VHTECCHGDLLECADDR (A) 265-281 Seq ID No 25 0,08 (R)FKDLGEENFK (A) 35-44 Seq ID No 26 0,03 (K)YICENQDSISSK (L) 287-298 Seq ID No 2270 0,02 (K)LDELRDEGK (A) 206-214 Seq ID No 28 0,01 (K)DDNPNLPR (L) 131-138 Seq ID No 29 -0,02 (K)LVNEVTEFAK (T) 66-75 Seq ID No 30 -0,08 (R)ETYGEMADCCAK (Q) 106-117 Seq ID No 3215 -0,37 (R)YKAAFTECCQAADK (A) 185-198 Seq ID No 32

[0002] Example 2 – Generation of the immunosuppressive albumin neo-structures by proteolytic degradation of human serum albumin by Stfaphylococcus aureus V-8 Protease. The capacity of bacterial proteases to degrade serum albumin to fragments exposing immunoregulatory neo-structures was investigated. Human serum albumin was incubated with and without the bacterial protease in three different buffers for four or 16 hours. As shown in Figure 2, the 3028 structure was generate already after four hours in buffer 1 and the amount of this albumin neo-structure was significantly enhanced after 16 hours. These results were confirmed using electrophoresis. By SDS-PAGE followed by Coomassie staining, albumin fragments of approx.50 and 10 kDa were discovered with the protease in Buffer 1 but not in the corresponding controls. Similar results were observed in incubation with the protease in Buffer 3 but not in the corresponding controls (Fig.3). Example 3 – Presence of an IL-6 inducing albumin neo-structure in human sera and its inhibition by antibodies directed to the 935-structure. The impact of 935-structures, in serum, on IL-6 synthesis was explored in PBMC cultures where cells from a healthy donor were exposed to heat inactivated sera from cancer patients or healthy donors. Oligoclonal rabbit antibodies directed against the 935- structure were added to half of the cultures in order to inhibit the IL-6 inducing structure in sera (Fig.4). Adding the 935 antibodies had no effect on IL-6 synthesis in culture with sera from two controls and one cancer patient (Fig 4). IgG and immune complexes can have a regulatory effect on IL-6 production by PBMC (Berger et al., 1996). Therefore, in parallel cultures, IgG and CIC were removed from the sera, by adsorption using protein-G Dynabeads. This procedure significantly enhanced the inhibitory effect of specific rabbit antibodies blocking the 935 -structure (Fig.5), indicating that cross-linking of FcR or FcR and the cellular receptor of IL-6IF might play an important role in regulation of IL-6 synthesis. Example 4 -- Programming of PBMCs in vivo To further explore the generation of immunoregulatory albumin neo-structures, increasing amounts of albumin were added to PBMC cultures and supernatants were collected after 24 hours. ELISA plates coated with rabbit antibodies directed to the 3208- and the 935-structures were incubated with culture supernatants. The amount of the bound neo-structure was determined by a secondary antibody directed against denatured albumin. Interestingly, significantly more of these albumin neo-structures were generated in PBMC cultures from advanced cancer patients compared to healthy controls (Fig.6). This indicates, that not only is there an enhanced amount of the IL-6 inducing neo- structure present in cancer patient sera, but such neo-structures can be produced selectively by PBMC from cancer patients, probably due to a unique set up of proteases or ROS. Example 5 -- Distribution of albumin neo-structures in tumours The distribution of the P935 neo-structure in human tumours was explored by histochemical staining using a rabbit anti-P935 antibody. As demonstrated in Figure 7 different staining patterns were obtained in four different human breast cancers. As seen in figure 7, in one tumor (A), the 935 structure is mainly expressed in inflammatory cells with macrophage morphology localized in the stroma, in tumour (B) and (C) this neo-structure is widely present in stromal areas and in tumour (D) the stroma and tumour cells show a strong expression of the 935-structure. A similar pattern was found in colorectal cancer. Two out of 10 representative tumours are shown. In tumour (A), IL-6 inducing factor is mainly confined to non-cellular stromal areas and some inflammatory cells with macrophage morphology, in tumour (B) a strong expression is found in inflammatory cells localized in the stroma. Some tumour cells are faintly stained but the majority do not express IL-6IF (Figure 8). These tumours were also stained for the occurrence of interleukin-6. Expression of this cytokine was found both in stroma and tumour cells. Examples of two tumours out of ten are shown in Figure 9. No correlation between occurrence of IL-6IF in the tumours and expression of IL-6 was found, probably because of the extensive heterogeneity of the tumours in the biopsies. Colorectal cancers were also stained for the occurrence of the 3028-neo-structure using oligoclonal rabbit antibodies . Two out of 10 stained cancers are shown (Fig. 10). Interestingly, this neo-structure has a remarkably different distribution compared to that of neo-structure 935, the stromal areas are almost negative with only a few scattered positive cells whereas the tumour cells generally are positive. This indicates a different cellular production of the 3028-neo-structure, in tumour cells, or possibly it is produced elsewhere and just taken up by the tumour cells. In contrast to the 935-neo-structure, inflammatory cells in the stroma do not seem to be major producers of the 3028-neo- structure. Example 6-- Immunogenicity of albumin neo-structures – Autoantibodies / AMPA against the albumin neo-structures 935 and 3028. Immunoregulation by albumin neo-structures is further complicated as some of these neo- structures, including P935 and 3028, are immunogenic, resulting in the production of autoantibodies (Fig. 11 and 12). The presence of both the antigen, that is albumin neo- structures, and the autoantibodies (anti-modified protein antibodies, AMPA) in vivo results in development of immune complexes. Consequently, the albumin neo-structures and autoantibodies exist in immune complexes and as free antigen and antibody depending on their ratio. In order to enable proper determination and clinical evaluation, the constituents of these complexes have to be further characterized. The concentration of autoantibodies directed against the 935- and 3028-structures were determined using the ELISA technique where the plates were coated with the 935- or the 3028-peptide and incubated with serum / plasma from healthy controls or patients. Followed by determination of bound antibodies using an anti-IgG antibody. The analyses of two types of samples are shown in Figure 11 and 12. Serum or plasma was diluted to 10% (dark bars) or diluted to 2% and heat inactivated at 56oC for 30 minutes (grey). Interestingly, it was found that standard heat inactivation of plasma or sera resulted in release of a large amount of free antibody. The antibody titre in sera diluted to 2% (five times more) and heat inactivated contain significantly more free antibodies than sera just diluted 10 times. Interestingly, in cancer the serum titre of such autoantibodies is significantly lower in advanced disease compared to healthy controls (p>0.0001), indicating an increased elimination of immune complexes due to a high production of the antigen. An additional cohort of samples from patients with colorectal cancer is shown in Figure 13. Example 7 -- Release of autoantibodies, AMPA, by heat inactivation Heat inactivation of sera, 56oC for 30 minutes, results in aggregation of albumin / albumin fragments with pathologically changed configuration, albumin neo-structures. This will block antigenic neo-structures and thereby reduce the number of antibody binding sites, resulting in release of free antibodies. The effect of heat inactivation of serum albumin is demonstrated in Fig.14, in this case using the albumin neo-structure 3028 (generated in the same way as the 935-structure). Aggregated albumin neo-structures in healthy and patient sera, as determined in this experiment, either expose detectable numbers of neo-structures to bind to the ELISA plates or the aggregates might slowly release epitope positive fragments over a wide concentration range when diluted (Fig. 14 A and B). In contrast to the situation with aggregated albumin, which shows a high constant concentration level until diluted at least 10000 times, the titre of autoantibodies released after heat inactivation gradually decreases during dilution (Fig. 14 C and D). Furthermore, the concentration of autoantibodies and albumin in cancer patient sera is, in good agreement with previous results, lower than that in healthy controls. Again, indicating elimination of immune complexes. Interestingly, as shown in previous studies (WO 03 / 099312 A1) heat inactivated sera have the capacity to stimulate IL-6 production despite a considerable aggregation of albumin neo-structures. The autoantibodies released by heat inactivation obviously do not have the capacity to bind to and block the albumin neo-structure formed during heat inactivation and released when the sera are diluted (Fig. 14). Either the amount of the dissociated neo-structure is sufficient for stimulation of IL-6 production or probably smaller albumin fragments with a low propensity to aggregate are present in patient sera in a higher concentration than in control sera. Albumin fragments of different size were actually demonstrated in previous ultrafiltration experiments. Alternatively, the neo- structures are exposed in immune complexes or aggregates and bind to the cellular receptor with a higher affinity than that between autoantibody and neo-structure. Example 8 – Purification and use of AMPA for further analyses of modified proteins, neo-structures AMPA directed against specific modified protein epitopes can be purified using affinity chromatography. The specific epitopes / peptide sequences are synthesized, biotinylated and bound to beads, e.g. streptavidin beads (magnetic beads or Sepharose beads). Such beads are incubated with natural or heat inactivated plasma / sera from healthy persons or patients, specific AMPA bind to the beads and can then be eluted or before elution the bound antibodies can be biotinylated and then be eluted. Such antibodies can be bound to streptavidin coated beads or protein-G Sepharose beads and can be used for purification / isolation of albumin neo-structures. Furthermore, antibodies bound to such beads can bind and inhibit the activity of specific modified proteins / immune complexes, exposing said epitope, from plasma / sera (See Example 11). The size of the modified proteins and the possible exposure of multiple other epitopes of importance for the binding avidity or crosslinking of targets can then be analyzed, using standard methods such as electrophoresis, gel filtration, ultrafiltration, Western blotting. Alternatively, in order to avoid heat inactivation of whole serum acid dissociation of IC can be used. IgG and IC in serum / plasma are bound to protein-G Sepharose (NB! without albumin binding structure), acidic elution will remove the antibodies from protein-G and dissociate IC. Before neutralization a surplus the biotinylated peptides / neo-structures of interest bound to streptavidin beads is added. Neutralization of the eluate will then enable binding of the antibodies to the beads. A surplus off the biotinylated peptide will competitively reduce the binding of antigen initially bound in IC. Thus, the specific AMPA will be bound to the beads and can be eluted and used for analytical or preparative procedures. The affinity purified specific AMPA / specific biotinylated AMPA described above can be used to determine a patient’s immune status by quantifying the specific modified protein / neo-structure of relevance for the patient’s condition in serum / plasma or other body fluids using for example the inhibition ELISA technique. In addition, these biotinylated specific AMPA can be used to study the occurrence and distribution of the specific immunoregulatory modified protein / neo- structure under investigation in biopsies of cancer or inflamed tissues. In the present investigation, such results have been obtained using oligoclonal rabbit antibodies directed against the modified protein sequences, e.g. P3028 and P935. Example 9 -- Occurrence of autoantibodies / AMPA directed against the albumin neo-structures P3028 and P935 in sera / plasma from patients with infectious diseases. Based on the general mechanisms involved in generation of immunoregulatory albumin neo-structures (enhanced proteolytic degradation or denaturation of normal serum albumin), the possible occurrence of this type of structures in severe infectious diseases was analysed. Interestingly, patients with such infectious diseases can have a significantly reduced serum concentration of autoantibodies against 3028- and 935- structures, which indicates that this immunosuppressor mechanism is active also in these diseases (Fig.15). Table 1. Diagnoses of the cohort of patients with severe infectious diseases presented in Figure 15. SAMPLE DIAGNOSIS NUMBER 1 Miliary tuberculosis (meningitis, spondylitis) 2 Tuberculosis (pulmonary) 3 Meningococcal meningitis 4 Brain abscess 6 Meningococcal meningitis 7 Sepsis (B fragilis, metastatic anal cancer) 8 Endocarditis 9 Endocarditis 10 Spondylitis (salmonella) 11 Septic arthritis (sepsis GAS) 12 Endocarditis 13 Endocarditis 14 Spondylitis (RA) 15 Spondylitis (epidural abscess, S aureus) 16 Spondylitis 18 Spondylitis 19 Septic arthritis (sepsis streptococci) 20 Septic arthritis (sepsis, S aureus) A second cohort of patients with infectious diseases are presented in Figure 16. Groups of striped and dark bars identify patients with repeated samples also during treatment. Twenty samples from 11 patients were analysed, 7 patients were analysed 2-3 times during the same care event, and 4 were tested only once. As controls, plasma and sera from healthy controls and plasma from advanced cancer patients were included. Patients with advanced cancer had a low concentration of autoantibodies directed to 3028-structures, low bars (Antibody binding, ABB<0.4). A similar pattern was also found in patients with severe infections whereas patients with less severe infections had a higher concentration of these autoantibodies (high bars). The most advanced patients were No 96 (pneumococcal sepsis), 194 (E.coli sepsis requiring intensive care), 429 (GAS infection with necrotizing fasciitis), 557 (GAS infection with necrotizing fasciitis). These patients had an ABB-value around or below 0.4. Interestingly, 6 days after initiation of treatment, the ABB-values improved considerably, to 0.6 - 1.0, indicating a reduced production of immunosuppressive 3028-structures after treatment (Fig. 16). The correlation to disease status is further demonstrated by patient No. 96 (pneumococcal sepsis) and 194 (serious sepsis requiring intensive care) with an ABB- value around 0.4 compared to patient No.93 (mild sepsis treated at an ordinary ward) with an ABB-value of 0.6 (Fig.16). Included in this cohort are also patients with less severe infections or inflammatory conditions; No 5 with erysipelas (ABB-value 0.7 to 0.9), No 102 diarreha due to toxin producing Clostridium difficile (ABB-value 1.1 to 0,7), No 109 with hemophagocytosis (ABB-value 0.9) and two patients with viral infections; No 309 with influenza and No 319 with Dengue fever (both with ABB-values around 1.0) . In parallel with the analyses of plasma of the second cohort of patients for the anti-3028-AMPA titre, the anti-935-AMPA titre was analysed (Fig. 18). The patient characteristics of these patients are given above. The variation of the 935-AMPA titres is very similar to that of the anti-3028-AMPA titre described above. The impact the anti- 935-AMPA titre on the IL-6 concentration in plasma from patients with the severe diagnoses, necrotizing fasciitis and septic shock are described in Example 10. Example 10 -- Correlation between anti-935 autoantibody / AMPA and serum concentration of il-6 in severe infectious diseases. Based on these observations a possible correlation between systemic exposure to the 935-structure, IL-6IF (low titre of autoantibodies directed against the peptide 935) and the serum concentration of IL-6 was investigated. When the auto-antibody titre increases after initiation of treatment, the serum concentration of IL-6 is significantly decreased (Fig.19). In patients with necrotizing fasciitis from 3000 pg / ml to zero and in the patient with septic shock from 300 pg / ml to zero. The serum concentration of IL-6 in the patient with “benign” sepsis is just 30 pg / ml and it does not seem to be influenced by the 935-structure. Taken together these early results show that the titre of anti-3028- and anti- 935- AMPA titres (indirect amount of immunosuppressive 3028-structures) produced in infectious diseases vary with the severity of the disease and that therapeutic measures reduce production of 935- and 3028-structures and thereby increased the specific AMPA titres. Further, the serum IL-6 concentration is correlated to the concentration of these neo-structures. Example 11 --Effect of autoantibodies / AMPA on IL-6 synthesis induced by peptide 935. As described above the 935 peptide has the capacity to induce IL-6 synthesis by PBMC. In one set of experiments, in order to avoid any influence of serum factors, the cultures were set up with a synthetic medium. Again, the 935-structure induced IL-6 synthesis, which was efficiently inhibited by incubation of the inducing medium with affinity purified AMPA directed against the 935-structure bound to protein-G beads (Fig. 20). This result strongly supports the regulatory effect of autoantibodies on IL-6 synthesis in vivo. Example 12 -- Correlation between autoantibody / AMPA titre and serum concentration IL-6 A possible correlation between the serum concentration of IL-6 and the occurrence of autoantibodies against the peptide 935, IL-6IF, was investigated. The serum concentration of Il-6 and autoantibodies against P935 in sera from colorectal cancer patients are presented in Table 5. A low concentration of these AMPA (auto-antibodies) is considered to be due to a high in vivo production of 935-strucutrs, which bind the antibodies, which are consumed by forming immune complexes which are eliminated. A low titer of autoantibodies thus indicates a high in vivo exposure to 935 structures. As shown in Fig. 21 a significant correlation was found between systemic exposure to P935, IL-6IF (indicate by low antibody titre) and the IL-6 serum concentration in these cancer patients. Thus, the serum titre of auto antibodies is inversely correlated to the serum concentration of IL-6 in colorectal cancer, indicating that a high titre of AMPA (autoantibodies) blocks the activity of IL-6IF. Table 2. Serum concentration of AMPA (auto-antibodies) directed against the 935 structure and the serum concentration of IL-6 in 10 colorectal cancer patients. Sera No. IL-6 (pg / mL) P935 AMPA G01 14.6 1.670 G02 3.1 2.732 G03 6.5 2.324 G04 12.7 2.530 G05 4.8 2.613 G06 5.6 3.273 G07 22.0 2.138 G08 5.4 3.175 G09 41.3 1.887 G10 3.7 2.911 Example 13 - Demonstration and quantification of albumin related neo- structures binding to immune cells – unblocking of LFA-1 The binding of immunoregulatory modified protein neo-structures to immune cell surface receptors modulates the function of these cells. Usually, either their production of cytokines or expression of cell surface receptors / markers is changed, either up or down-regulated, as in endotoxin tolerance, immune paralysis, immunosuppression in for example cancer or sepsis or enhanced cytokine production, hyperactivation, cytokine storm. These neo-structures are generated by pathological processes, protein degradation by an enhanced proteolytic activity or enhanced denaturation of proteins, resulting in dysregulation of the normal function of the immune system. Removal of these neo-structures from their cell receptors, will therefore result in normalization of the function of the immune system. The removal can be achieved by incubation with specific AMPA or corresponding monoclonal antibodies. Monoclonal antibodies directed against integrin epitopes, often have profound immunoregulatory activity. Endogenously generated immunogenic modified protein neo- structures binding to the same epitope / structure most likely have a corresponding immunoregulatory activity. Modified protein neo-structures do exert their regulatory function by binding to specific receptors / epitopes on immune cells. AMPA or corresponding monoclonal antibodies binding to the same neo-structures will compete with the cellular receptors / epitopes for the binding of the neo-structures. Consequently, incubation by such AMPA, in solution or bound to micro beads, will have the capacity to remove the binding and blocking neo-structures from their cellular receptor, thereby enabling an enhanced binding of the monoclonal antibodies directed to these receptors / epitopes. In this case the binding of an anti-CD11a monoclonal antibody (clone HI 111) to normal PBMCs after pre-incubation with normal plasma or cancer patient plasma is demonstrated. Three of the cancer patient sera clearly block the binding of the antibody (Fig.22). Interestingly, these serum factors, blocking the binding of anti-integrin monoclonal antibodies to the cells, can be removed by antibodies directed to albumin neo-structures, in this case anti-3028 antibodies or a short peptide complementary to, binding and inhibiting the 3028-structure. In this experiment the MEM 48 antibody directed to the β-chain of LFA-1 was used (Fig.23). In Fig.23, images are shown of PBMCs showing the restoration of anti-CD18 binding by addition of anti-P3028 or P30. Normal PBMCs were incubated with cancer patient plasma, followed by anti-P3028 antibodies or P30, and staining using the anti- CD18 antibody, MEM48 (strong dark membrane staining around the cells): In the figure can be seen: A. Control, binding of CD18 antibody after incubation with plasma from a healthy individual. B. Inhibition of CD18 antibody binding after incubation with plasma from a cancer patient. C. Incubation with cancer patient plasma followed by anti-P3028 antibodies showing restitution of the binding of the anti-CD18 antibody. D. Incubation with cancer patient plasma followed by incubation with the peptide P30 showing restitution of the binding of the anti-CD18 antibody. This method demonstrates the occurrence of cell bound immunoregulatory modified protein neo-structures and enables their quantification by measuring the binding of competitive monoclonal antibodies, in this case anti-integrin antibodies. Example 14 – Diagnostic methods based on Example 13 The technique described in Example 13 can be used for the diagnosis of the immune status of patients with inflammation related disease using three alternative methods: A: Immune cells from patients with pathological conditions are isolated and incubated with AMPA or corresponding monoclonal antibodies in order to remove cell bound modified proteins / neo-structures. These cells are then cultured in the absence of neo-structures in a medium with or without stimulation, with for example PHA, ConA, PWM or LPS, for a suitable number of days. The production of cytokines, e.g. pro-and anti-inflammatory, determined intra-cellularly or in culture supernatants from cells, incubated and not incubated with specific antibodies / AMPA, is then determined by Flow Cytometry, e.g. the Luminex technique. Similarly, cells from such cultures are harvested and the expression of cell surface markers before and after AMPA incubation is determined using Flow Cytometry. B: In order to reduce the variability of the method and to in order to facilitate analyses of multiple samples the individual patient immune cells are substituted for by a pool of standardized immune cells expressing the relevant cell surface receptor. These cells are incubated with serum from the patient to be tested, which results in binding of neo-structures in the serrum to the cells. After washing the cells are incubated with specific antibodies / AMPA and stained as described under point A. C: In order to further standardize the method, for blocking and unblocking cell surface receptors, individual patient immune cells are substituted for by microbeads or ELISA plates coated with integrins, exposing the binding sites of the modified protein neo-structures under investigation. The micro beads are incubated with patient serum / plasma, which results in binding of neo-structures in the serum to the beads / plates . After washing the cells are incubated with specific antibodies / AMPA for unblocking and stained as described under point A. Example 15 – Determinatnion of the functional impact of single or combined AMPA and their corresponding neo-structures The methods according to Example14 can be performed either using specific AMPA or corresponding monoclonal antibodies or total AMPA or combined AMPA or corresponding monoclonal antibodies. In the former case the immune parameter related to only one neo-structure will be analyzed. Using total AMPA or combined AMPA or corresponding monoclonal antibodies will disclose the total dysregulation by immunogenic immunoregulatory neo-structures in that particular patient. The specific immunomodulation can then be further analyzed by using specific AMPA or corresponding monoclonal antibodies. The technique with total AMPA / corresponding monoclonal antibodies is of particular interest as dysregulation of the immune system often is multi-factorial and attempts over decades trying only one immunomodulatory correction at a time usually has failed. Now the panel of dysregulatory neo-structures and AMAP can be revealed, based on which a correct selection of neo-structures to be therapeutically removed / inhibited / blocked can be identified. In this context the recently developed technique to produce recombinant polyclonal antibodies can be useful (e.g. Rapid Novor). Example 16 -- Determination of albumin neo-structure in sera from patients with infectious diseases using inhibition ELISA Next an inhibition ELISA for determination of the IL-6 inducing albumin neo- structure 935 in sera / plasma from healthy controls and patients with various IL-6 related diseases such as patients with cardiovascular disease, infectious and inflammatory diseases and cancer was set up. Antibodies directed against albumin neo-structures released from immune complexes by heat inactivation as described above were bound to protein-G coated ELISA plates. The biotinylated 935 peptide or a biotinylated 10 amino acid long sequence of this peptide, L10, were used as probes binding to the antibody coated ELISA plates. Simultaneous incubation with sera containing the IL-6 inducing structures will compete with the binding of the probes and reduce their binding. Thereby giving a measure of the amount of the IL-6 inducing factor in serum. As seen in Figure 24 patients with infectious diseases have significant inhibition of the binding of the probes, that is a significantly enhanced concentration of albumin neo-structures in plasma. Example 17-- Determination of the IL-6 inducing albumin neo-structure in sera from cancer patients using inhibition ELISA The concentration of the IL-6 inducing factor, the neo-structure-935 in controls and patient sera competing with the biotinylated probes P935 or L10 were analysed in a first series of colon cancer patients stadium I and IV. The serum concentration of this neo- structure is significantly increased in both stages (inhibiting the binding of the probes) and is significantly higher in more advanced colon cancer patients comparing stage I and IV. (Fig.25). Next the serum concentration of the IL-6 inducing albumin neo-structure was further analysed in all four stages of colon cancer. The difference in concentration of the 935- neo-structure in colon cancer patients, stadium I – IV is shown in Table 3 and Figure 26. Table 3. Serum concentration of the IL-6 inducing albumin neo-structure 935 according to stage of colon cancer. DUNNETT'S MULTIPLE MEAN 95,00% CI OF SUMMARY COMPARISONS TEST DIFF, DIFF, BASE SIGNAL VS. STAGE I 0,1278 to *** BASE SIGNAL VS. STAGE II 0,1458 to BASE SIGNAL VS. STAGE III 0,2366 to BASE SIGNAL VS. STAGE IV 0,2674 to Both probes demonstrate a stage dependent increase of the serum concentration of the albumin neo-structure 935 (inhibition of the binding of the probes). Exampe 18 - Identification of other immunoregulatory modified proteins and corresponding AMPA A large number of anti-integrin antibodies with immunoregulatory activity have been described. Several of these antibodies have been shown to compete with the binding of modified albumin neo-structures to the integrin structure (Davis, 1992). AMPA with an antigen binding structure binding to and blocking such neo-structures binding to the integrin should have the property of acting as anti-idiotype antibody directed against the anti-integrin antibody binding to the same integrin sequence as the integrin binding albumin neo-structure. That this is actually the case is shown in an ELISA (Figure 27) where three different anti-integrin antibodies were found to bind to AMPA bound to a protein-G coated coated plate. Identification of such clinically relevant, immunogenic, immunoregulatory modified protein albumin neo-structures is done using this method: Chips / peptide array with modified albumin neo-structures of known sequences (Hansen et al.,2013) are incubated with total AMPA from patients and healthy controls and AMPA which will bind to the specific, corresponding structures on the chip Addition of the anti-integrin antibody to such incubations will block the binding of the specific AMPA to the chip as its idiotype will bind to the idiotype of the specific AMPA. Thus, the corresponding albumin neo-structure on the chip will be identified with no bound AMPA compared to incubations in the absence of the anti-integrin antibody. The modified protein, albumin neo-structures identified in this way are synthesized and characterized as described in this application. Example 19 – Prognostic significance of the albumin neo-structure inducing IL-6 in serum from colon cancer patients – Survival analysis Total AMPA released by heat inactivation were bound to protein-G ELISA plates, which were incubated overnight with the sera / plasma to be tested. The following day, the plates were washed carefully and incubated with the probe. IL-6 inducing albumin neo- structures present in sera compete with the probe and inhibit its binding to the autoantibodies bound to the protein-G plate. The serum concentration of these neo- structures (inhibitory units, low binding of the probe) was significantly enhanced in sera from colon cancer patients who died because of their cancer (Table 4). The discriminatory level was set to be 0.7. Eight stage III patients in the high IL-6IF group (low probe binding group) had died from their cancer, four were still alive after five years. In the group with low IL-6IF seven stage III patients were still alive after five years. The Kaplan Meier analysis is shown in Fig.28. A high serum concentration of IL-6IF was significantly associated with poor survival (p<0.0080, Logrank test). Table 4. Results from inhibition ELISA showing Inhibitory Units for stage II and III colon cancer. Patient Tumour Inhibitory Patient Tumour Inhibitory No stage units No stage units 1 2 1,320 21 3 0,973 220,975 2230,768321,671 2330,695420,909 2430,737521,015 2530,601621,019 2630,628720,933 2730,778820,949 2830,705921,187 2930,6161021,017 3030,6951120,803 3130,9331220,779 3230,7121320,778 3330,6251420,652 3430,6071520,944 3530,5681620,663 3630,6171720,873 3730,6625 1820,616 3830,6701920,868 3930,6432020,750 4030,796Example 20 – Production of recombinant polyclonal antibodies As described under Example 15, the possibility to simultaneously diagnose multiple dysregulatory mechanism in the immune system based on immunogenic albumin neo-structures can be very valuable as pathological dysregulation of the immune system often is multifactorial. Further, correction of this dysregulation by recombinant polyclonal antibodies (Papid Novor) based on sequencing of AMPA identified as described here creates a new therapeutic strategy. In this technique polyclonal antibodies are sequenced. The antibodies are degraded by a special panel enzyme generating a mixture of peptides, which are identified using LC-MS / MS. These sequences are then put together using a special algorithm as for example described by Rapid-Novor and recombinant polyclonal antibodies are produced. Example 21 – Identify B-cells, CDR-squences and develop recombinant monoclonal antibodies Specific human monoclonal antibodies can be developed using the single B-cell technique. As several of the pathogenic immunoregulatory albumin neo-structures are immunogenic eliciting an immune response with production of AMPA, the corresponding, antibody producing B-cell from patients or healthy controls can be identified and isolated by standard techniques. These cells are then be sequenced identifying the CDR sequences, which are used for production of recombinant monoclonal antibodies. This technique is now a standard procedure. Thus, the low titer of AMPA, too low to inhibit the pathogenic mechanisms of albumin neo-structures in advanced patients, can be therapeutically corrected by administration of such monoclonal antibodies. Example 22 - Production of IL-6 inducing factors by adding serum albumin or immunoglobulin G (IvIg) to washed tumor homogenates or activated matrix metalloproteases (MMPs) In order to further explore the nature of immunomodulating fragments in tumors, thoroughly washed tumor homogenates, with no IL-6 inducing activity, were incubated with serum albumin or IvIg in order to study if tumor tissue (Fig.29) or MMPs (Fig.30) have the capacity to generate active fragments from these proteins. It was then found that addition of IgG and in particular albumin markedly increased the production of IL-6 inducing factor. The cytokine inducing activity was analyzed in cultures with normal PBMCs and IL-6 production was determined using the ELISA technique. Based on the quantitative differences between IvIg and albumin, the sequence homogeneity of albumin and the correlation between the albumin neo-structure IL-6IF and cancer specific survival, albumin neo-structures were further explored in this patent application. Example 23 – Demonstration of the therapeutic activity of affinity purified antibodies directed against the IL-6 inducing albumin neo-structure IL-6IF (P935). In order to demonstrate the therapeutic activity of antibodies directed against the IL-6 inducing, albumin derived, factor IL-6IF, affinity purified antibodies were added to sera from patients with colon cancer stage IV and the effect was analyzed in an inhibition ELISA as described above. As can be seen in Figure 31, the binding of the probe 935 to the ELISA plates was markedly inhibited (dark grey bars) when only patient serum was added compared to the base signal level (black bar). When antibodies directed against IL- 6IF was added to the sera, the binding of the probe was significantly increased (purple bars), that is the antibodies bound the serum factors thereby blocking their inhibition of the binding of the probe to the ELISA plates. This is exactly what has to be achieved in order to control pathological IL-6 production in patients. - - - - - Interestingly, this patent application describes a diagnostic test based the occurrence of IL-6 inducing albumin neo-structures in patients with severe infectious diseases and advanced cancer and the correlation between such neo-structures and survival of cancer patients. Furthermore, a therapeutic strategy for these cancer patients was made possible as specific human antibodies with the capacity to inhibit the activity of the IL-6 inducing neo-structure were identified and purified. Thus, the neo-structures, inducing IL-6 production, associated with a reduced survival of cancer patients can be selectively removed, by therapeutic administration of antibodies with the specificity described here, leaving the function of IL-6 needed for the normal activity of the immune system intact. Although the present invention has been described above with reference to (a) specific embodiment(s), it is not intended to be limited to the specific form set forth herein. Rather, the invention is limited only by the accompanying claims and, other embodiments than the specific above are equally possible within the scope of these appended claims, e.g. different than those described above. In the claims, the term "comprises / comprising" does not exclude the presence of other elements or steps. Furthermore, although individually listed, a plurality of means, elements or method steps may be implemented by e.g. a single unit or processor. Additionally, although individual features may be included in different claims, these may possibly advantageously be combined, and the inclusion in different claims does not imply that a combination of features is not feasible and / or advantageous. In addition, singular references do not exclude a plurality. The terms "a", "an", “first”, “second” etc do not preclude a plurality. Reference signs in the claims are provided merely as a clarifying example and shall not be construed as limiting the scope of the claims in any way. References Berger S, Balló H, Stutte HJ. Immune complex-induced interleukin-6, interleukin-10 and prostaglandin secretion by human monocytes: a network of pro- and anti-inflammatory cytokines dependent on the antigen:antibody ratio. Eur J Immunol. 1996 Jun;26(6):1297-301. doi: 10.1002 / eji.1830260618. PMID: 8647208. Davis GE. The Mac-1 and p150,95 beta 2 integrins bind denatured proteins to mediate leukocyte cell-substrate adhesion. Exp Cell Res.1992 Jun;200(2):242-52. doi: 10.1016 / 0014-4827(92)90170-d. PMID: 1572393 Hansen LB, Buus S, Schafer-Nielsen C. Identification and mapping of linear antibody epitopes in human serum albumin using high-density Peptide arrays. PLoS One.2013 Jul 23;8(7):e68902. doi: 10.1371 / journal.pone.0068902. PMID: 23894373; PMCID: PMC3720873 Cabiedes J, Cabral AR, Alarcon-Segovia D. Identification of four subpopulations of IgG anticardiolipin antibodies in patients with primary antiphospholipid syndrome on the basis of their requirement for beta 2-glycoprotein-I and their unmasking by heat. Clin Exp Rheumatol.1994 Mar-Apr;12(2):123-7. PMID: 8039278. Hu X, An T, Situ B, Hu Y, Ou Z, Li Q, He X, Zhang Y, Tian P, Sun D, Rui Y, Wang Q, Ding D, Zheng L. Heat inactivation of serum interferes with the immunoanalysis of antibodies to SARS-CoV-2. J Clin Lab Anal.2020 Sep;34(9):e23411. doi: 10.1002 / jcla.23411. Epub 2020 Jun 28. PMID: 32594577; PMCID: PMC7361150

Claims

CLAIMS 1. A method for identifying, or characterizing specific autoantibodies, associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, comprising: - preparing modified protein neo-structure fragments, - incubating a body fluid sample from a healthy individual (control) with said modified protein neo-structure fragments, - identifying, characterizing, and / or quantifying any autoantibodies binding to the modified protein neo-structure fragments, - incubating a body fluid sample from a patient with inflammation or a dysregulated immune system with the same modified protein neo- structure fragments, - identifying, characterizing and / or quantifying any specific autoantibodies binding to the modified protein neo-structure fragments, and - correlating or comparing the levels or amount or type or sequence of the captured autoantibodies for healthy individuals and with the levels or amount or type or sequence of the captured autoantibodies from patients with inflammation or a dysregulated immune system for each protein neo-structure fragment, wherein different or altered specific autoantibody level or amount or type or sequence of the captured autoantibodies between the healthy individual and a patient with a normal or dysregulated immune system or inflammation indicates that both the specific protein neo-structure fragment and the specific antibody are connected to the inflammation or the dysregulated immune system.

2. The method according to claim 1, wherein the method further comprises: - affinity purifying the captured specific autoantibodies connected to the inflammation or the dysregulated immune system,- incubating a body fluid from a patient with inflammation or a dysregulated immune system with said affinity purified specific autoantibodies, and identifying, characterizing and quantifying any modified protein neo-structure fragments binding to said specific autoantibodies, wherein the identified specific protein neo-structure fragment can be connected to the inflammation or the dysregulated immune system.

3. The method according to claim 1 or 2, wherein the specific autoantibodies are anti-modified protein antibodies (AMPA).

4. The method according to any one of claims 1 to 3, wherein the modified protein neo-structure fragments are albumin neo-structures.

5. The method according to any one of claims 1 to 4, wherein the protein neo- structure fragments may be bound to chips, beads ELISA plates or peptide arrays.

6. The method for according to any one of claims 1 to 5, wherein the body fluid sample is selected from or derived from whole blood or fractions thereof, blood plasma, blood serum, lymph fluid, urine, cerebrospinal fluid, saliva, exudates such as synovial fluid, ascites or pleural effusions or tissues including biopsies / samples from infectious or inflamed tissues, lymph nodes, or tumours including the tissue microenvironment.

7. The method according to any one of claims 1 to 6, wherein the body fluid sample is a blood plasma, sera or urine sample.

8. The method according to any one of claims 1 to 7, wherein the body fluid sample is heat inactivated before the incubation, whereby any autoantibodiesthat are part of immune complexes (IC) are released and become free / unbound autoantibodies into the body fluid sample.

9. The method according to claim 8, wherein the heat activation uses a temperature of between 50 to 70oC and an incubation time of between 5 to 60 minutes, such as a temperature of 50 to 60oC and an incubation time of 15 to 45 minutes.

10. The method according to any one of claims 1 to 9, wherein protein G beads are used to capture any IgG and immune complexes in the body fluid sample.

11. The method according to claim 10, wherein, wherein any autoantibodies part of any IgG and immune complexes are released by acidic elution and then captured by a surplus of modified protein neo-structures bound to beads during neutralization of the eluate.

12. The method according to any one of claims 1 to 11, the modified protein neo- structure fragments are the result of enhanced proteolytic fragmentation and / or denaturing in an inflammatory tissue and / or a malignant tumour, resulting in a conformational change of a normally occurring serum protein.

13. The method according to any one of claims 1 to 12, wherein the modified protein neo-structure fragments is derived from any protein that after modification bind to cellular receptors, e.g. albumin, fibrinogen or extracellular matrix (ECM) proteins.

14. The method according to any one of claims 1 to 13, wherein the modified protein neo-structure fragments are from a immune cell surface binding modified protein.

15. The method according to any one of claims 1 to 14, wherein the modified protein neo-structure fragments are derived from human serum albumin.

16. The method according to any one of claims 1 to 15, wherein the modified protein neo-structure fragments are derived from human serum albumin and can modify cytokine production, expression of cell surface structures or immune cell function.

17. The method according to any one of claims 1 to 16, wherein the modified protein neo-structure fragments are derived from human serum albumin and can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cells.

18. A method according to claim 17, wherein the IL-6 production is determined using one or more standard tests.

19. The method according to any one of claims 1 to 18, wherein the pathological condition related to or caused by inflammation or a dysregulated immune system is an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or a cancer, such as a colorectal cancer or a head and neck cancer, such as cancer types associated with IL-6, such as Hematological Cancers or Solid Tumor Cancers, such as multiple myeloma, leukemia (such as Acute myeloid leukemia (AML)), Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Lymphoma (such as Hodgkin lymphoma or Non-Hodgkin lymphoma), Breast cancer, Prostate cancer, Lung cancer (such as Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC)), Colorectal cancer, Pancreatic cancer, Ovarian cancer, Liver cancer (Hepatocellular carcinoma), Renal cell carcinoma, Gastric cancer, Bladder cancer, Head and neck cancers (such as Oral cancer, Pharyngeal cancer, Laryngeal cancer), and Sarcomas (such as Osteosarcoma, Ewing sarcoma or Soft tissue sarcoma).

20. The method according to any one of claims 1 to 19, wherein the pathological condition related to or caused by inflammation or a dysregulated immune system is an infectious diseases selected from: severe infection caused by any microbe, sepsis, septic shock or severe viral infection, such as Covid-19.

21. The method according to any one of claims 1 to 20, wherein the modified protein neo-structure fragments and autoantibodies have the capacity to dysregulate or normalize the function of the immune system and thereby cause or alleviate severe symptoms or play a pathogenic role in the pathological condition.

22. The method for according to any one of claims 1 to 21, wherein the dysregulation of the immune system is characterized by immune overstimulation / hyperstimulation, including a cytokine storm, and / or any type of immune suppression.

23. The method according to any one of claims 1 to 22, wherein the modified protein neo-structure fragment is an albumin neo-structure with known amino acid sequence.

24. The method according to any one of claims 1 to 23, wherein the modified protein neo-structure fragments has an amino acid sequence of between 10 to 100 AA length, such as 15 to 50 AA length and comprises (or comprises a fragment of) or is selected from SEQ ID NO: 1 (FSALEVDETYVPKEFNAETFTFHAC) or SEQ ID NO: 2 (VFDEFKPLVEEPQNLIK), or having a % sequence identity (SI) of at least 80%, such as at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with SEQ ID NO: 1 or SEQ ID NO: 2, or an amino acid sequence having the sequence of SEQ ID NO: 1 or 2, wherein any one, two, three, or four amino acids are substituted, preferably with a conservative amino acid substitution.

25. An antibody or binding fragment thereof, which specifically binds to a modified protein neo-structure fragment associated with a pathological condition related to or caused by inflammation or a dysregulated immune system according to any one of claims 1 to 24.

26. The antibody or binding fragment thereof according to claim 25, wherein the antibody or binding fragment thereof blocks, inhibits, eliminates or decreases immunoregulatory activity of said modified protein neo-structure fragment.

27. The antibody or binding fragment thereof according to claim 25 or 26, wherein the antibody or binding fragment thereof is a monoclonal antibody or binding fragment thereof, a recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof.

28. A monoclonal antibody, recombinant monoclonal antibody or a recombinant polyclonal antibody, or a binding fragment thereof, wherein the antibody or binding fragment thereof is an anti-modified protein human or humanized antibody or binding fragment thereof, which blocks, eliminates or decreases the activity of an immunoregulatory anti-modified protein associated with a pathological condition related to or caused by inflammation or a dysregulated immune system in a subject.

29. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof according to claim 28, wherein the immunoregulatory anti-modified protein is an immune cell surface binding modified protein.

30. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonalantibody or binding fragment thereof according to claim 28 or 29, wherein the immunoregulatory anti-modified protein is derived from a human serum albumin, which can modify cytokine production, expression of cell surface structures or immune cell function.

31. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof according to any one of claims claim 28 to 30, wherein the immunoregulatory modified protein is derived from a human serum albumin, which can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cells.

32. A pharmaceutical composition comprising the antibody or binding fragment thereof according to any of claims 25 to 31 and a pharmaceutically acceptable carrier, excipient or stabilizer.

33. A method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein in a body fluid sample from a patient, modified proteins and / or autoantibodies that have been linked to a specific pathological condition using the method of claims 1 to 24 are identified and determined, whereby the presence of such a modified protein neo-structure fragment and / or autoantibody binding to the modified protein neo-structure fragment is used to identify that the patient suffers from the specific pathological condition, such as a cancer, inflammation or a dysregulated immune system.

34. The method according to claim 33, wherein the occurrence of a modified protein neo-structure fragment and / or an autoantibody binding to the modified protein neo-structure fragment is used to establish the prognosis of the patient suffering from the specific pathological condition, such as a cancer, such ascancer types associated with IL-6, such as Hematological Cancers or Solid Tumor Cancers, such as multiple myeloma, leukemia (such as Acute myeloid leukemia (AML)), Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Lymphoma (such as Hodgkin lymphoma or Non-Hodgkin lymphoma), Breast cancer, Prostate cancer, Lung cancer (such as Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC)), Colorectal cancer, Pancreatic cancer, Ovarian cancer, Liver cancer (Hepatocellular carcinoma), Renal cell carcinoma, Gastric cancer, Bladder cancer, Head and neck cancers (such as Oral cancer, Pharyngeal cancer, Laryngeal cancer), and Sarcomas (such as Osteosarcoma, Ewing sarcoma or Soft tissue sarcoma).

35. A method of stimulating an immune response in a subject, comprising administering to a subject in need thereof an antibody or a binding fragment thereof, according to any of claims 25 to 31, or a pharmaceutical composition comprising said antibody or binding fragment thereof according to claim 32, in an amount effective to stimulate or control the immune response.

36. A method of inhibiting a pathological immune response in a subject, comprising administering to a subject in need thereof an antibody or binding fragment thereof according to any of claims 25 to 31, in an amount effective to inhibit the immune response.

37. A method for modulating an inflammatory response in a subject, comprising administering to the subject an effective amount of an antibody or binding fragment thereof according to any of claims 25 to 31, wherein the antibody or binding fragment thereof is a human or humanized antibody or binding fragment thereof, which blocks, inhibits, eliminates or decreases the activity of an immunoregulatory modified protein neo-structure fragment in the subject.

38. A method of treating or inhibiting a pathological condition related to or caused by inflation or a dysregulated immune system, comprising administering to a subject in need thereof an antibody or binding fragment thereof of any of claims 25 to 31, or a pharmaceutical composition according to claim 32, in an amount effective to treat a pathological condition related to or caused by a dysregulated immune system.

39. The method according to claim 38 wherein the pathological condition related to or caused by inflammation or a dysregulated immune system is an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or a cancer.

40. The method according to any one of claims 38 to 39, wherein the pathological condition is and infectious diseases selected from severe infection caused by any microbe, in particular sepsis, septic shock or severe viral infection, such as Covid-19.

41. The method according to any one of claims 38 to 40, wherein the antibody or binding fragment thereof specifically binds to an immunoregulatory albumin neo-structure.

42. A method for treating or inhibiting, or ameliorating a disease by blocking, inhibiting, eliminating or decreasing the activity of an immunoregulatory modified protein neo-structure fragment in a subject, by administering to the subject an effective amount of a monoclonal or a recombinant polyclonal antibody or binding fragment thereof according to any one of claims 25 to 31 or a pharmaceutical composition according to claim 32.

43. A method for identifying and characterizing immune parameters related to an autoantibody binding to a modified protein neo-structure fragment, or a modified protein neo-structure fragment, wherein in an isolated sample of immune cells from a patient with a pathological condition; the isolated immune cells are divided into two cell portions; the first immune cell portion is incubated with antibodies with the same specificity as autoantibodies associated with a pathological condition related to or caused by inflammation or a dysregulated immune system according to any one of claims 1 to 24, in order to remove cell bound modified protein neo-structures; the first and second immune cell portion are cultured separately in a medium for at least one day, and the production of cytokines in the medium or the expression of cell surface markers or the function of each immune cell portion is determined.

44. The method according to claim 43, wherein epitope specific autoantibodies or antibodies with the same specificity are used to remove cell bound modified protein neo-structure fragments, whereby the immune parameter related to only one neo-structure will be analyzed.

45. The method according to claim 43 or 44, wherein total, all types of AMPA including all released antibodies in the serum or antibodies with the corresponding specificities are used to remove cell bound modified protein neo-structure fragments, whereby the total dysregulation by immunogenic immunoregulatory neo-structure fragments in that particular patient will be analyzed.

46. The method according to claim 45, wherein the antibodies are produced as recombinant polyclonal antibodies.

47. A method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein immune parameters related to a modified protein neo-structure fragment are identified and characterized in an isolated sample of immune cells from a patient with a pathological condition using the method according to any one of claims 43 to 46, whereby it can be determined which modified protein neo-structures are involved in immunoregulation in the patient.

48. A method for identifying and characterizing surface cell receptor expression related to an autoantibody or modified protein neo-structure, wherein in an isolated sample of immune cells from a patient with a pathological condition; the isolated immune cells are divided into two cell portions, where the second immune cell portion is incubated with antibodies with the same specificity as autoantibodies associated with a pathological condition related to or caused by a dysregulated immune system according to any one of claims 1 to 24, in order to remove cell bound modified protein neo- structures; cells from the first and the second immune cell portion are harvested; and expression of surface cell markers are determined for the harvested cells from the first immune cell portion and for the second immune cell portion, or the first and second immune cell portion are cultured separately in a medium for at least one day, and expression of surface cell markers are determined for these cells from the first immune cell portion and for the second immune cell portion,whereby any change in expression of surface cell receptors between the harvested immune cells of the first cell portion, comprising cell bound modified protein neo-structures, and the harvested immune cells of the second portion, where antibodies has removed cell bound modified protein neo-structures, can be determined.

49. The method according to claim 48, wherein the expression of cell surface markers is determined using Flow Cytometry.

50. The method according to claim 48 or 49, wherein epitope specific antibodies with the same specificity as autoantibodies are used to remove cell bound modified protein neo-structures, or total autoantibodies including all released antibodies in the serum are used to remove cell bound modified protein neo- structures.

51. A method for identifying, isolating, characterizing or quantifying autoantibodies specific for one or more modified protein neo-structure fragments associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, comprising: - preparing one or more modified protein neo-structure fragments, - incubating a body fluid sample from a healthy individual (control) with said one or more modified protein neo-structure fragments, and - identifying, isolating, characterizing, or quantifying autoantibodies from the body fluid sample from the healthy individual binding to the one or more modified protein neo-structure fragments, or - incubating a body fluid sample from a patient having inflammation or a dysregulated immune system with said one or more modified protein neo-structure fragments, and- identifying, isolating, characterizing or quantifying autoantibodies from the body fluid sample from the patient having inflammation or a dysregulated immune system, which bind to the one or more modified protein neo-structure fragments, - optionally, comparing the levels of captured autoantibodies for healthy individuals and patients having inflammation or a dysregulated immune system for each one or more modified protein neo-structure fragment, wherein a different / altered specific autoantibody level between the healthy individual and a patient having inflammation, or a dysregulated immune system indicates that both the modified protein neo-structure fragment and the isolated antibody are associated with a pathological condition related to or caused by inflammation or a dysregulated immune system.

52. The method according to claim 51, wherein the method further comprises: - affinity purifying the autoantibodies from the healthy individuals and / or the patients with inflammation or a dysregulated immune system, which bind to the one or more modified protein neo-structure fragments and, - optionally, incubating a body fluid from a patient with inflammation or a dysregulated immune system with said affinity purified specific autoantibodies and, - optionally, identifying, isolating, characterizing and / or quantifying the modified protein neo-structure fragments binding to said affinity purified specific autoantibodies.

53. The method according to claim 51 or 52, wherein the specific autoantibodies are anti-modified protein antibodies (AMPA).

54. The method according to any one of claims 51 to 53, wherein the modified protein neo-structure fragments are albumin neo-structures.

55. The method according to any one of claims 51 to 54, wherein the modified protein neo-structure fragments are bound to chips, beads ELISA plates or peptide arrays.

56. The method for according to any one of claims 51 to 55, wherein the body fluid sample is selected from or derived from whole blood or fractions thereof, blood plasma, blood serum, lymph fluid, urine, cerebrospinal fluid, saliva, exudates such as synovial fluid, ascites or pleural effusions or tissues including biopsies / samples from infectious or inflamed tissues, lymph nodes, or tumours including the tissue microenvironment.

57. The method according to any one of claims 51 to 56, wherein the body fluid sample is a blood plasma, sera or urine sample.

58. The method according to any one of claims 51 to 57, wherein the body fluid sample is heat inactivated before the incubation under conditions sufficient to release autoantibodies that are part of immune complexes (IC) so as to produce free / unbound autoantibodies in the body fluid sample.

59. The method according to claim 58, wherein the conditions sufficient to release autoantibodies that are part of immune complexes (IC) comprise heat activation at temperature of between 50 to 70oC and an incubation time of between 5 to 60 minutes, such as a temperature of 50 to 60oC and an incubation time of 15 to 45 minutes.

60. The method according to any one of claims 1 to 9, wherein protein G beads are used to capture IgG and immune complexes in the body fluid sample.

61. The method according to claim 10, wherein, wherein autoantibodies, which are part of IgG and immune complexes are released by acidic elution and captured with modified protein neo-structures bound to beads, preferably during neutralization of the eluate.

62. The method according to any one of claims 1 to 11, wherein the modified protein neo-structure fragments are produced by enhanced proteolyticfragmentation and / or denaturing in an inflammatory tissue and / or a malignant tumour, resulting in a conformational change of a serum protein.

63. The method according to any one of claims 1 to 12, wherein the modified protein neo-structure fragments are derived from a protein that after modification binds to cellular receptors, e.g. albumin, fibrinogen or one or more extracellular matrix (ECM) proteins.

64. The method according to any one of claims 1 to 13, wherein the modified protein neo-structure fragments are from an immune cell surface binding modified protein.

65. The method according to any one of claims 1 to 14, wherein the modified protein neo-structure fragments are derived from human serum albumin.

66. The method according to any one of claims 1 to 15, wherein the modified protein neo-structure fragments are derived from human serum albumin and can modify cytokine production, expression of cell surface structures or an immune cell function.

67. The method according to any one of claims 1 to 16, wherein the modified protein neo-structure fragments are derived from human serum albumin and can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cells.

68. A method according to claim 17, wherein the IL-6 production is determined using one or more standard tests.

69. The method according to any one of claims 1 to 18, wherein the pathological condition related to or caused by inflammation, or a dysregulated immune system is an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or a cancer, such as colorectal cancer or a head and neck cancer, such as cancer types associated with IL-6, such as Hematological Cancers or Solid Tumor Cancers, such as multiple myeloma, leukemia (such as Acute myeloid leukemia (AML)),Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Lymphoma (such as Hodgkin lymphoma or Non-Hodgkin lymphoma), Breast cancer, Prostate cancer, Lung cancer (such as Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC)), Colorectal cancer, Pancreatic cancer, Ovarian cancer, Liver cancer (Hepatocellular carcinoma), Renal cell carcinoma, Gastric cancer, Bladder cancer, Head and neck cancers (such as Oral cancer, Pharyngeal cancer, Laryngeal cancer), and Sarcomas (such as Osteosarcoma, Ewing sarcoma or Soft tissue sarcoma).

70. The method according to any one of claims 1 to 19, wherein the pathological condition related to or caused by inflammation, or a dysregulated immune system is an infectious diseases selected from: a severe infection caused by a microbe, sepsis, septic shock or a viral infection, such as Covid-19.

71. The method according to any one of claims 1 to 20, wherein the modified protein neo-structure fragments and autoantibodies have the capacity to dysregulate or normalize the function of the immune system and thereby cause or alleviate severe symptoms or play a pathogenic role in the pathological condition.

72. The method for according to any one of claims 1 to 21, wherein the dysregulation of the immune system is characterized by immune overstimulation or hyperstimulation, such as a cytokine storm, or immune suppression.

73. The method according to any one of claims 1 to 22, wherein the one or more modified protein neo-structure fragments are an albumin neo-structure with a known amino acid sequence.

74. The method according to any one of claims 1 to 23, wherein the one or more modified protein neo-structure fragments have an amino acid sequence of between 15 to 50 amino acids in length and have a sequence comprising or consisting of SEQ ID NO: 1 (FSALEVDETYVPKEFNAETFTFHAC) or SEQID NO: 2 (VFDEFKPLVEEPQNLIK), an amino acid sequence having a % sequence identity (SI) of at least 80%, such as at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with SEQ ID NO: 1 or SEQ ID NO: 2 or an amino acid sequence having the sequence of SEQ ID NO: 1 or 2, wherein any one, two, three, or four amino acids are substituted, preferably with a conservative amino acid substitution.

75. An antibody or binding fragment thereof such as an scFv domain, which can be presented on a cell (e.g., a chimeric antigen receptor T cell) or a support, wherein said antibody or binding fragment thereof specifically binds to a modified protein neo-structure fragment associated with a pathological condition related to or caused by inflammation or a dysregulated immune system, isolated or characterized according to any one of claims 1 to 24, such as a monoclonal antibody or binding fragment thereof, a recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof, which specifically binds to an amino acid sequence comprising or consisting of SEQ ID NO: 1 (FSALEVDETYVPKEFNAETFTFHAC) or SEQ ID NO: 2 (VFDEFKPLVEEPQNLIK), an amino acid sequence having a % sequence identity (SI) of at least 80%, such as at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with SEQ ID NO: 1 or SEQ ID NO: 2 or an amino acid sequence having the sequence of SEQ ID NO: 1 or 2, wherein any one, two, three, or four amino acids are substituted, preferably with a conservative amino acid substitution.

76. The antibody or binding fragment thereof according to claim 25, wherein the antibody or binding fragment thereof blocks, inhibits, eliminates or decreases immunoregulatory activity of said one or more modified protein neo-structure fragments.

77. The antibody or binding fragment thereof according to claim 25 or 26, wherein the antibody or binding fragment thereof is a monoclonal antibody or binding fragment thereof, a recombinant monoclonal antibody or bindingfragment thereof or a recombinant polyclonal antibody or binding fragment thereof.

78. A monoclonal antibody, recombinant monoclonal antibody or a recombinant polyclonal antibody, or a binding fragment thereof, wherein the antibody or binding fragment thereof is an anti-modified protein human or humanized antibody or binding fragment thereof, which blocks, eliminates or decreases the activity of an immunoregulatory anti-modified protein associated with a pathological condition related to or caused by inflammation or a dysregulated immune system in a subject isolated by any one of the claims 1 to 24.

79. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or a binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof according to claim 28, wherein the immunoregulatory anti-modified protein is an immune cell surface binding modified protein.

80. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or a binding fragment thereof or a recombinant polyclonal antibody or binding fragment thereof according to claim 28 or 29, wherein the immunoregulatory anti-modified protein is derived from a human serum albumin, which can modify cytokine production, expression of cell surface structures or immune cell function.

81. The monoclonal antibody or binding fragment thereof, recombinant monoclonal antibody or binding fragment thereof or a recombinant polyclonal antibody or a binding fragment thereof according to any one of claims claim 28 to 30, wherein the immunoregulatory modified protein is derived from a human serum albumin, which can induce production of interleukin-6 by cells, e.g. normal immune cells, tumor cells, fibroblasts or endothelial cells.

82. A pharmaceutical composition comprising the antibody or binding fragment thereof according to any of claims 25 to 31 and a pharmaceutically acceptable carrier, excipient or stabilizer.

83. A method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein: in a body fluid sample from a patient, modified proteins or autoantibodies that have been linked to a specific pathological condition using the method of claims 1 to 24 are identified and determined, whereby: the presence of such a modified protein neo-structure fragment or autoantibody binding to the modified protein neo-structure fragment is used to verify that the patient suffers from the specific pathological condition.

84. The method according to claim 33, wherein the occurrence of a modified protein neo-structure fragment or an autoantibody binding to the modified protein neo-structure fragment is used to establish the prognosis of the patient suffering from the specific pathological condition.

85. A method of stimulating an immune response in a subject, comprising: administering to a subject in need thereof an antibody or a binding fragment thereof according to any of claims 25 to 31, or a pharmaceutical composition according to claim 32, in an amount effective to stimulate or control the immune response.

86. A method of inhibiting a pathological immune response in a subject, comprising: administering to a subject in need thereof an antibody or binding fragment thereof according to any of claims 25 to 31, in an amount effective to inhibit the immune response.

87. A method for modulating an inflammatory response in a subject, comprising: administering to the subject an effective amount of an antibody or binding fragment thereof according to any of claims 25 to 31, wherein the antibody or binding fragment thereof is a human or humanized antibody or binding fragment thereof, which blocks, inhibits, eliminates or decreases the activity of an immunoregulatory modified protein neo-structure fragment in the subject.

88. A method of treating or inhibiting a pathological condition related to or caused by inflammation or a dysregulated immune system, comprising administering to a subject in need thereof an antibody or binding fragment thereof of any of claims 25 to 31, or a pharmaceutical composition according to claim 32, in an amount effective to treat or inhibit a pathological condition related to or caused by a dysregulated immune system.

89. The method according to claim 38 wherein the pathological condition related to or caused by inflammation, or a dysregulated immune system is an infectious disease, a chronic inflammatory disease, an autoimmune disease, a metabolic syndrome, type 2 diabetes, neurodegenerative disease, cardiovascular disease or a cancer, such as colorectal cancer or head and neck cancer, such as colorectal cancer or head and neck cancer, such as cancer types associated with IL-6, such as Hematological Cancers or Solid Tumor Cancers, such as multiple myeloma, leukemia (such as Acute myeloid leukemia (AML)), Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Lymphoma (such as Hodgkin lymphoma or Non-Hodgkin lymphoma), Breast cancer, Prostate cancer, Lung cancer (such as Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC)), Colorectal cancer, Pancreatic cancer, Ovarian cancer, Liver cancer (Hepatocellular carcinoma), Renal cell carcinoma, Gastric cancer, Bladder cancer, Head and neck cancers (such as Oral cancer, Pharyngeal cancer, Laryngeal cancer), and Sarcomas (such as Osteosarcoma, Ewing sarcoma or Soft tissue sarcoma).

90. The method according to any one of claims 38 to 39, wherein the pathological condition is an infectious disease selected from an infection caused by a microbe, in particular sepsis, septic shock or a viral infection, such as Covid- 19.

91. The method according to any one of claims 38 to 40, wherein the antibody or binding fragment thereof specifically binds to an immunoregulatory albumin neo-structure.

92. A method for treating or inhibiting a disease by blocking, inhibiting, eliminating, or decreasing the activity of an immunoregulatory modified protein neo-structure fragment in a subject, by administering to the subject an effective amount of a monoclonal or a recombinant polyclonal antibody or binding fragment thereof according to any one of claims 25 to 31 or a pharmaceutical composition according to claim 32.

93. A method for identifying and characterizing immune parameters related to an autoantibody binding to a modified protein neo-structure fragment, or a modified protein neo-structure fragment, comprising: preparing two cell portions from an isolated sample of immune cells obtained from a patient that has a pathological condition, incubating a first immune cell portion with antibodies having the same specificity as autoantibodies associated with a pathological condition related to or caused by inflammation or a dysregulated immune system according to any one of claims 1 to 24, to remove cell bound modified protein neo-structures; incubating a second immune cell portion, wherein the first and second immune cell portions are cultured separately in a medium for at least one day, and determining the production of one or more cytokines, the expression of one or more cell surface markers or the function of at least one of the prepared immune cell portions.

94. The method according to claim 43, wherein epitope specific autoantibodies or antibodies with the same specificity are used to remove cell bound modified protein neo-structure fragments, whereby the immune parameter related to only one neo-structure is analyzed.

95. The method according to claim 43 or 44, wherein the total of all types of AMPA including all released antibodies in the serum or antibodies with the corresponding specificities are used to remove cell bound modified protein neo-structure fragments, whereby the total dysregulation by immunogenicimmunoregulatory neo-structure fragments in that particular patient will be analyzed.

96. The method according to claim 45, wherein the antibodies are produced as recombinant polyclonal antibodies.

97. A method of diagnosing a pathological condition related to or caused by inflammation or a dysregulated immune system, wherein immune parameters related to a modified protein neo-structure fragment are identified and characterized in an isolated sample of immune cells from a patient with a pathological condition using the method according to any one of claims 43 to 46, whereby it can be determined which modified protein neo-structures are involved in immunoregulation in the patient.

98. A method for identifying and characterizing surface cell receptor expression related to an autoantibody or modified protein neo-structure, wherein: dividing an isolated sample of immune cells from a patient having a pathological condition into a first immune cell portion and a second immune cell portion, wherein the second immune cell portion is incubated with antibodies having the same specificity as autoantibodies associated with a pathological condition related to or caused by a dysregulated immune system according to any one of claims 1 to 24, in order to remove cell bound modified protein neo- structures; harvesting cells from the first and the second immune cell portions; and determining the expression of surface cell markers on the harvested cells from the first immune cell portion and for the second immune cell portion, or culturing the first and second immune cell portion separately in a medium for at least one day, and determining the expression of surface cell markers on the first immune cell portion and the second immune cell portion, whereby a change in expression of surface cell receptors between the harvested immune cells of the first cell portion, comprising cell bound modified protein neo-structures, and theharvested immune cells of the second portion, wherein the antibodies have removed cell bound modified protein neo-structures, are determined.

99. The method according to claim 48, wherein the expression of cell surface markers is determined using Flow Cytometry.

100. The method according to claim 48 or 49, wherein epitope specific antibodies with the same specificity as autoantibodies are used to remove cell bound modified protein neo-structures, or total autoantibodies including all released antibodies in the serum are used to remove cell bound modified protein neo-structures.

Images