Minimally invasive diagnosis method of canine disorders
Patent Information
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- MARS INC
- Filing Date
- 2024-08-30
- Publication Date
- 2026-07-08
AI Technical Summary
Current methods for diagnosing canine skin disorders, such as atopic dermatitis, are invasive and traumatic, limiting their use in early detection and repetitive sampling, and they do not allow for the detection of disorders before clinical signs appear.
A minimally invasive method involving the application of adhesive tape to collect epidermal samples from canine skin, which are then analyzed for specific protein and nucleic acid biomarkers indicative of immunological, inflammatory, or Th2 immune responses.
This method enables the reproducible detection and quantification of biomarkers in canine skin samples, allowing for early detection of skin disorders, assessment of treatment effects, and monitoring of disease flares with reduced discomfort and risk of infection for the animal.
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Figure US2024044697_06032025_PF_FP_ABST
Abstract
Description
[0001]MINIMALLY INVASIVE DIAGNOSIS METHOD OF CANINE DISORDERS CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to European Patent Application No. 23306455.9 filed on August 31, 2023, the contents of which are incorporated herein by reference in its entirety. FIELD OF THE DISCLOSURE The present disclosure relates to the field of diagnosis of inflammatory and non- inflammatory disorders in canine skin, which include allergic disorders such as canine atopic dermatitis. BACKGROUND OF THE DISCLOSURE Diagnosis of diseases or disorders in canine is conventionally performed through skin biopsies. Skin biopsies are an important diagnostic tool used by veterinarians to gather information about a wide range of skin disorders and diseases in dogs. A skin biopsy involves the removal of a small sample of skin tissue for examination. The information obtained from the biopsy can help determine the underlying cause of skin issues and guide appropriate treatment. Indeed, skin biopsies which are necessarily traumatic, are generally performed once clinical signs are already detectable. Thus, invasive methods are generally not practiced at an early stage of the suspected disorder or disease. Consequently, beyond being traumatic for the animal, skin biopsies are of restricted use in large scale clinical trials and longitudinal studies. Minimal invasive methods are desirable to enable more dynamic and repetitive skin sampling over time, including in relation treatment, environment, and disease flares. Further, it is desirable to reduce canine’s discomfort, potential infection and scarring caused by biopsies, including by skin biopsies. Further, minimal invasive methods are also desirable because they can allow detecting the risk of occurrence of a disorder or of a disease before its occurrence. Alternatively, minimal invasive methods can allow assessing the actual occurrence of a disorder or of a disease at an early stage after its onset, especially before any clinical sign become apparent. In human, some minimally invasive diagnosis methods are disclosed in the art, including those comprising collecting skin samples by tape stripping. Sampling human skin material by tape stripping is thus known in the art, notably with the aim of studying skin physiological parameters, such as in subjects affected with skin disorders such as atopic dermatitis. Human skin samples can be collected and studied as regards their content in proteins (Clausen et al., 2020, Nature Research.10 : 21895), or as regards their content in nucleic acid material, such as their content in mRNA (Dyjack et al., 29, J Allergy Clin Immunol, Vol.141 (4) : 1298-1309) or microRNA (Morlang et al., 2021, Vet Dermatol, Vol.32 : 331 – e92). There is still a need in the art for the provision of minimally invasive methods for qualifying and / or quantifying proteins in a canine skin sample, particularly with the goal of performing a canine diagnosis, notably a canine diagnosis of skin disorders or diseases, being either non-inflammatory or inflammatory disorders or diseases, such as canine atopic dermatitis. SUMMARY The present text relates to method for detecting or measuring the content of one or more selected protein biomarkers and / or one or more nucleic acid biomarkers in a canine skin sample, including the steps of: a) applying an adhesive tape to an exposed skin target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, and b) detecting the presence of, and / or measuring the content of, the said one or more selected protein biomarker and / or one or more nucleic acid biomarker in the epidermal sample obtained at step a). In a particular embodiment, at step b) the one or more selected protein and / or nucleic acid canine biomarkers can be indicative of a canine immunological state. In another embodiment, at step b) the one or more selected protein and / or nucleic acid canine biomarkers can be canine biomarkers indicative of a canine inflammatory response. In another embodiment, at step b) the one or more selected protein and / or nucleic acid canine biomarkers can be canine biomarkers indicative of a canine Th2 immune response. In particular, the one or more selected protein and / or nucleic acid canine biomarkers can be chosen among proteins present in the epidermis. In particular, the one or more selected proteins present in the epidermis can be chosen among: a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL-31) and interleukin-33 (IL-33) ; b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^) ; and / or c) thymic stromal lymphopoietin (TSLP); and / or d) one or more proteins selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL- 22), interleukin-4 receptor (IL-4R), and a combination thereof. In a particular embodiment, detecting the presence of and / or measuring the content of, a selected protein biomarker at step b) can be performed by an immunological method. In particular, the one or more selected nucleic acid biomarkers can be selected from mRNA and miRNA. In particular, wherein detecting the presence of and / or measuring the content of a selected mRNA or miRNA biomarker at step b) can be performed by a nucleic acid amplification method. A further object of the present text relates to method of determining the presence of a cutaneous disorder state in a canine skin including the steps of: a) applying an adhesive tape to an exposed target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, b) detecting a statistically significantly different level of one or more protein and / or one or more nucleic acid canine biomarkers in the said epidermal sample, c) determining the presence of a cutaneous disorder when a statistically significantly different level of one or more of the said biomarkers is measured at step b). In particular, the said cutaneous disorder can be an inflammatory disorder, preferentially selected from canine atopic dermatitis, pyoderma, contact dermatitis, folliculitis, acne, seborrheic dermatitis, panniculitis, cellulitis, lick granuloma (acral lick dermatitis, histiocytoma, eosinophilic granuloma complex) nasal solar dermatitis (collie nose), interdigital cysts and furunculosis, ichtyosis, dermodicosis (dermodectic mange), ringworm (dermatophytosis) and vasculitis. In particular, the said cutaneous disorder can be a non-inflammatory disorder, preferentially selected from alopecia aerate, colordilution alopecia, pattern baldness, congenital hypotrichosis, hyperketatosis, sebaceous adenitis, follicular dysplasia, dermoid sinus, X- linked ichtyosis, cyclic follicular dysplasia, nasal planum hyperkeratosis, hereditary footpad hyperkeratosis, primary seborrhea, vitamin A-responsive dermatosis, cutaneous mastocytosis, hypothyroidism-associated skin changes and canine epidermolysis bullosa. The text further relates to a method for the diagnosis of an atopic dermatitis state in a canine skin including the steps of: a) applying an adhesive tape to an exposed skin target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, b) detecting statistically significantly different level of one or more protein and / or nucleic acid canine biomarkers in the said epidermal sample, , c) determining the presence of an atopic dermatitis state when a statistically significantly different level of one or more of the said protein and / or nucleic acid canine said biomarkers is measured at step b), and d) one or more protein and / or nucleic acid canine biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. In particular, the said protein and / or nucleic acid canine biomarkers can be selected from: a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin- 13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL-31) and interleukin-33 (IL-33) ; b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^); and c) thymic stromal lymphopoietin (TSLP) and d) one or more protein and / or nucleic acid canine biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. Further, the present text relates to a method of determining the beneficial effect of a pharmaceutical agent and / or of a selected diet regimen in a canine affected with an atopic dermatitis including the steps of: a) applying an adhesive tape to an exposed skin target area of the said canine, whereby an epidermal sample adhering to the adhesive tape is collected, b) measuring the level of, one or more selected protein and / or nucleic acid canine biomarker in the said epidermal sample collected at step b), c) subjecting the said canine to a treatment with a pharmaceutical agent and / or with a selected diet regimen, d) applying an adhesive tape to an exposed skin target area of the said canine, whereby an epidermal sample adhering to the adhesive tape is collected, e) detecting, and / or measuring the level of, one or more selected protein and / or nucleic acid canine biomarker in the said epidermal sample collected at step d), f) determining a beneficial effect of the said pharmaceutical agent and / or the said diet regimen when an increase and / or a decrease in the level of one or more of the biomarkers is measured at step e) when compared with the level of the same selected biomarker that was measured at step b). In particular, step a) (and step d)) can comprise: a1) (and d1) applying an adhesive tape from about 1 to about 50 times, preferentially from about 10 to about 30 times, on an exposed target area of the skin of said canine to remove the superficial layer of the skin, most preferably to remove the stratum corneum thereof, and a2) (and d2) applying an adhesive tape, distinct from the adhesive tape of step a1), to an exposed skin target area of the said canine, whereby an epidermal sample adhering to the adhesive tape is collected. In particular, in each of steps a) and d), the adhesive tape can be applied at a constant pressure. Further, said protein or nucleic acid canine biomarkers can be selected from: a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL- 13), interleukin-25 (IL-25), interleukin-31 (IL-31) and interleukin-33 (IL-33) ; b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^); c) thymic stromal lymphopoietin (TSLP); and d) one or more protein or nucleic acid canine biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin- 13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL- 4R), and a combination thereof. Further, the present text relates to a kit of parts for detecting and / or or measuring protein and / or nucleic acid canine biomarkers in a canine epidermal sample, including: a) one or more adhesive tapes for tape stripping skin, b) a reagent for collecting an epidermal sample adhered to a surface of an adhesive tape, c) reagents for detecting and / or quantifying one or more protein biomarkers, and / or d) reagents for detecting and / or quantifying one or more nucleic acids, in particular for detecting and / or quantifying one or more mRNAs or miRNAs, e) optionally, recommendations for using the kit of parts. BRIEF DESCRIPTION OF THE FIGURES The following figures are included to illustrate certain aspects of the present disclosure and should not be viewed as exclusive embodiments. The subject matter disclosed is capable of considerable modifications, alterations, combinations, and equivalents in form and function, without departing from the scope of this disclosure. Figure 1 : Comparison of the Elisa fold changes (log2 scale) and response status for dogs 5 and 6 for TNF. The dog IDs are indicated inside the dots. Figure 2 : Comparison of the Elisa fold changes (log2scale) and response status for dogs 5 and 6 for IL13. The dog IDs are indicated inside the dots. Figure 3 : Comparison of the transcriptomic and Elisa expression values for dogs 5 and 6 for TNF. The line is the linear regression line. The dog IDs are indicated inside the dots. Figure 4 : Comparison of the transcriptomic and Elisa expression values for dogs 5 and 6 for IL13. The line is the linear regression line. The dog IDs are indicated inside the dots. Figure 5 : Comparison of the transcriptomic fold changes (log2 scale) and response status for dog 5 and 6 for TNFRSF4 (ENSCAFG00845022948). The dog IDs are indicated inside the dots. Figure 6 : Comparison of the transcriptomic fold changes (log2 scale) and response status for dogs 5 and 6 for FA2H (ENSCAFG00845025633). The dog IDs are indicated inside the dots. Figure 7 : Comparison of the transcriptomic fold changes (log2 scale) and response status for dogs 5 and 6 for IL1B (ENSCAFG00845011661). The dog IDs are indicated inside the dots. Figure 8 : Comparison of the transcriptomic fold changes (log2 scale) and response status for dogs 5 and 6 for IL13RA1 (ENSCAFG00845019238). The dog IDs are indicated inside the dots. Figure 9: Comparison of the transcriptomic fold changes (log2 scale) and response status for dogs 5 and 6 for IL13RA2 (ENSCAFG00845016176). The dog IDs are indicated inside the dots. Figure 10: Comparison of the transcriptomic fold changes (log2scale) and response status for dogs 5 and 6 for IL22 (ENSCAFG00845013728). The dog IDs are indicated inside the dots. Figure 11: Comparison of the transcriptomic fold changes (log2scale) and response status for dogs 5 and 6 for IL4R (ENSCAFG00845004286). The dog IDs are indicated inside the dots. DETAILED DESCRIPTION Definitions The terms used in this specification generally have their ordinary meanings in the art, within the context of this disclosure and in the specific context where each term is used. Certain terms are discussed below, or elsewhere in the specification, to provide additional guidance in describing the compositions and methods of the disclosure and how to make and use them. Exemplary methods and materials are described below, although methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. Units, prefixes, and symbols are denoted in their International System of Units (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range. The headings provided herein are not limitations of the various aspects of the disclosure. Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety. All publications and other references mentioned herein are incorporated by reference in their entirety. As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a compound” can include a mixture of at least two compounds. The term “about” or “approximately”, as used herein, means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. In general, the term “about” can modify a numerical value above and below the stated value by a variance of, for instance, 10 percent, up or down (higher or lower). In some embodiments, the term indicates deviation from the indicated numerical value by ±15%, ±10%, ±5%, ±4%, ±3%, ±2%, or ±1%. As used herein, the terms “comprise”, “comprising”, “include”, “including” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a food composition, a process or a method that comprises a list of elements or ingredients which does not include only those elements or ingredients but can include other elements or ingredients not expressly listed or inherent to such food composition, process or method. The term “consisting of” implies the inclusion of the stated element(s), to the exclusion of any additional elements. The term “consisting essentially of” implies the inclusion of the stated elements, and possibly other element(s) where the other element(s) do not materially affect the basic and novel characteristic(s) of the disclosure. It is understood that the different embodiments of the disclosure using the term “comprising” or equivalent cover the embodiments where this term is replaced with “consisting of” or “consisting essentially of”. In the detailed description herein, references to “embodiment,” “an embodiment,” “one embodiment,” “in some embodiments,” or any other variation thereof, indicate that the described embodiment(s) can include a particular feature, ingredient, structure, or characteristic, but every embodiment might not necessarily include the particular feature, ingredient, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular feature, ingredient, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of one skilled in the art to affect such feature, ingredient, structure, or characteristic in connection with other embodiments whether or not explicitly described. After reading the description, it will be apparent to one skilled in the relevant art(s) how to implement the disclosure in alternative embodiments. As used herein, the term “canine” may include animals, including companion animals selected from recognized dog breeds (some of which are further subdivided), which may include Afghan hound, airedale, akita, Alaskan malamute, basset hound, beagle, Belgian shepherd, bloodhound, border collie, border terrier, borzoi, boxer, bulldog, French bulldog, bull terrier, bullmastiff, cairn terrier, chihuahua, chow, cocker spaniel, collie, corgi, dachshund, dalmatian, doberman, shar pei, English setter, fox terrier, German shepherd, golden retriever, great Dane, greyhound, griffon bruxellois, Irish setter, Irish wolfhound, King Charles spaniel, Labrador retriever, lhasa apso, mastiff, newfoundland, old English sheepdog, papillion, Pekingese, pointer, pomeranian, poodle, pug, rottweiler, St. Bernard, saluki, samoyed, schnauzer, Scottish terrier, Shetland sheepdog, shih tzu, Siberian husky, Skye terrier, vizsla, Rhodesian, Staffordshire terrier, Jack terrier, springer spaniel, West Highland terrier, whip companion, Yorkshire terrier, bichon, etc. As used herein, "Skin" means the outermost protective covering of mammals, especially canine, includes three main layers, an external epidermal (epidermis) layer, middle dermal (dermis) layer and a bottom hypodermal (hypodermis) layer. The epidermis layer comprises itself five layers which are, from the top (exposed to the environment) to the bottom (in contact with the dermis), (i) the stratum corneum, (ii) the stratum lucidum, (iii) the stratum granulosum, (iv) the stratum spinosum and (v) the stratum basale. As used herein, "Tape stripping" means a minimally invasive method of collecting biological material, especially proteins and nucleic acids (e.g. mRNAs and miRNAs) involving the use of an adhesive disposed on a skin substrate, especially of a canine skin substrate. According to the present disclosure, tape stripping is used to collect biological material, especially proteins and nucleic acids (e.g. mRNAs and miRNAs) from the surface of the canine skin by contacting a suitable adhesive containing substrate with the surface of the canine skin such that the biological material adheres to the adhesive. As used herein, the terms “skin disorder” or “skin diseases” or “dermatopathies” are meant to refer to a wide range of conditions that affect the skin's appearance, function, and health. These disorders can manifest as various changes in the skin's texture, color, structure, and overall condition. Skin disorders can result from genetic factors, infections, immune system reactions, environmental factors, allergies, hormonal imbalances, and other underlying causes. They may affect the outermost layer of the skin (epidermis), the deeper layers (dermis), or both. As used herein, the term “inflammatory disease” is meant to refer to any disease / disorder associated with inflammation, without restrictions, including those associated with one selected from an allergic (or atopic) disorder, an inflammatory skin disorder, an inflammatory digestive tract disorder, and a respiratory tract disorder. For example, the term may encompass one or more of the following conditions and syndromes: an atopic disease, Feline Atopic Syndrome (FAS), Feline Atopic Skin Syndrome (FASS), Feline asthma, Feline food allergy (FFA). The term further encompasses allergic dermatitis, allergic enteritis and asthma. As used herein, the term “non-inflammatory disease” is meant to refer to a medical condition or disorder that does not primarily involve inflammation as a major component of its pathology. Non-inflammatory diseases often have different underlying causes and mechanisms compared to inflammatory conditions. They can arise from genetic factors, metabolic imbalances, structural abnormalities, hormonal disturbances, or other non-immune-related sources. Non-inflammatory diseases can affect various organs and systems of the body and can lead to a wide range of symptoms and clinical manifestations. As used herein, the term “atopy” or “atopic disease” is meant to refer to the commonly acknowledged definition, without restrictions. The essential features of an atopic disease are defined as a predisposition to allergic disease affecting the skin. Hence, the term encompasses any clinical dermatitis hypersensitivity associated with an inherited tendency to produce immunoglobulin E (IgE) antibodies in response to environmental proteins such as pollen, house dust mite, and food allergens. As used herein, “Atopic dermatitis” (AD) means an inflammatory skin disease characterized by intense pruritus (e.g., severe itch) and by scaly and dry eczematous lesions. The term “atopic dermatitis” includes, but is not limited to, AD caused by or associated with epidermal barrier dysfunction, allergy (e.g., allergy to certain foods, pollen, mold, dust mite, animals, etc.), radiation exposure, and / or asthma. The present disclosure encompasses methods for determining the occurrence of, or the risk of occurrence of, moderate-to-severe or severe AD. As used herein, “moderate-to-severe AD”, is characterized by intensely pruritic, widespread skin lesions that are often complicated by persistent bacterial, viral or fungal infections. Moderate-to-severe AD also includes chronic AD in canine. In many cases, the chronic lesions include thickened plaques of skin, lichenification and fibrous papules. Canine affected by moderate-to-severe AD also, in general, have more than 20% of the body's skin affected, or 10% of skin area in addition to involvement of the eyes, feet and body folds. Moderate-to-severe AD can also be present in canine undergoing treatment with topical corticosteroids. A canine can also, in some cases, be said to have moderate-to-severe AD when the canine is resistant or refractory to treatment by either a topical corticosteroid or a calcineurin inhibitor. “Marker” “markers”, “biomarker”, or “biomarkers”, refers herein to a protein or a nucleic acid (e.g. mRNA or miRNA) that is expressed in a cell or tissue, which is useful for assessing a physiological state of a canine, including a non-inflammatory state, an inflammatory state or an immunological state of a canine, especially a dog, which encompasses the prediction or diagnosis of a disorder or a disease such as an inflammatory response. A protein marker or biomarker in the context of the present disclosure encompasses, for example, cytokines, chemokines, growth factors, other proteins and peptide. A nucleic acid marker or biomarker in the context of the present disclosure encompasses, for example, cytokines-encoding mRNAs, chemokines-encoding mRNAs, growth factors-encoding mRNAs and other proteins-encoding mRNAs. Examples of nucleic acid markers or biomarkers include, but are not limited to, FLG, LOR, IVL, CCL11, CCL13, CCL17, CCL18, CCL22, CCL18, CCL26, CCL27, CCL28, CXCL1, CXCL9, CXCL10, CXCL20, IL36R, IL18, IL6, IL7, IL15, IL17Rb, IL23, S100A12, S100A8, MMP12, MAN1A1, TNFRSF4, and FCER1A. According to the present disclosure, nucleic acid biomarkers encompass mRNAs and miRNAs. As used herein, the term “mRNA” or “messenger RNA”, refers to any polynucleotide which encodes at least one peptide or polypeptide of interest and which is capable of being translated to produce the encoded peptide polypeptide of interest in vitro, in vivo, in situ or ex vivo. An mRNA can be isolated from tissues or cells by a variety of methods. For example, a total RNA extraction can be performed on cell-containing sample, such as a canine epidermal sample, and the resulting extracted total RNA can be purified (e.g., on a column comprising oligo-dT beads) to obtain extracted mRNA. As used herein, the term “microRNA” or “miRNA” refers to an RNA interferent (RNAi) agent that is approximately 21-23 nucleotides (nt) in length. miRNAs can range between 18-26 nucleotides in length. Typically, miRNAs are single-stranded. However, in some embodiments, miRNAs may be at least partially double-stranded. In certain embodiments, miRNAs may comprise an RNA duplex (referred to herein as a “duplex region”) and may optionally further comprises one or two single-stranded overhangs. In some embodiments, an RNAi agent comprises a duplex region ranging from 15 to 29 bp in length and optionally further comprising one or two single-stranded overhangs. An miRNA may be formed from two RNA molecules that hybridize together, or may alternatively be generated from a single RNA molecule that includes a self-hybridizing portion. In general, free 5′ ends of miRNA molecules have phosphate groups, and free 3′ ends have hydroxyl groups. The duplex portion of an miRNA usually, but does not necessarily, comprise one or more bulges consisting of one or more unpaired nucleotides. One strand of an miRNA includes a portion that hybridizes with a target RNA. In certain embodiments of the invention, one strand of the miRNA is not precisely complementary with a region of the target RNA, meaning that the miRNA hybridizes to the target RNA with one or more mismatches. In other embodiments of the invention, one strand of the miRNA is precisely complementary with a region of the target RNA, meaning that the miRNA hybridizes to the target RNA with no mismatches. Typically, miRNAs are thought to mediate inhibition of gene expression by inhibiting translation of target transcripts. However, in some embodiments, miRNAs may mediate inhibition of gene expression by causing degradation of target transcripts. As used herein, the terms “statistically significantly different level”, “differential level” or “differential expression” of a protein or a nucleic acid (e.g. mRNA or miRNA) may include any increased or decreased level in a tested canine as compared with a reference level of the said protein or of the said nucleic acid of a healthy canine, more particularly with a canine which is not affected with an inflammatory disorder or disease, and even more particularly with a canine which is not affected with a cutaneous inflammatory disorder or disease, such as a canine which is not effected with atopic dermatitis. In one embodiment, statistically significantly different level means a level that is increased by: at least 5%; by at least 10%; by at least 20%; by at least 30%; by at least 40%; by at least 50%; by at least 60%; by at least 70%; by at least 80%; by at least 90%; by at least 100%; by at least 110%; by at least 120%; by at least 130%; by at least 140%; by at least 150%; or more. In another embodiment, statistically significantly different level means a level that is decreased by: at least 5%; by at least 10%; by at least 20%; by at least 30%; by at least 40%; by at least 50%; by at least 60%; by at least 70%; by at least 80%; by at least 90%; by at least 100%. As used herein, the term “food composition”, “wet food composition”, “nutritionally complect wet food composition” or “diet” covers all of foodstuff, diet, food supplement or a material that can contain proteins, fibers, carbohydrates and / or fats, which can be used in the body of an organism to sustain growth, repair and vital processes and to furnish energy. Carbohydrates includes NFE (Nitrogen free extract). A food composition can also contain supplementary substances or additives, for example, flavoring, minerals and vitamins. A food composition according to the present disclosure can consist of a nutritionally complete food composition. In some particular embodiments, a wet food composition according to the present disclosure can be a nutritionally complete wet food composition. As used herein, “nutritionally complete” means that the composition of the present disclosure provides the complete and balanced nutritional requirement to a companion animal, such as a cat or a dog. Specifically, a nutritionally complete food composition can contain all known required nutrients for the intended recipient of the food composition, in all appropriate amounts and proportions based, for example, on recommendations of recognized and competent authorities in the field of animal nutrition. Therefore, a nutritionally adequate diet is a diet with which the said companion animal can be fed as the sole ration and is capable of sustaining life without additional food (except water). The nutritionally complete food composition can further contain a carrier, a diluent, and / or an excipient. Depending on the intended use, the carrier, diluent, and / or excipient can be chosen to be suitable for companion animal use, especially for companion animals use such as feline and canine. Further, said nutritionally complete food composition can cause no significant change in the companion animal, i.e., body weight and / or also in the Body Condition Score (BCS). Illustratively, a food composition as described herein can include, but is not limited to, protein, fat, ash, fiber (TDF), carbohydrates, starch, calcium, phosphorus, sodium, chloride, Sodium tripolyphosphate, potassium, magnesium, iron, water, copper, manganese, zinc, selenium, flavouring, vitamin A, vitamin D3, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin B7, vitamin B9, cholin chloride, arachidonic acid, W3 fatty acid or W6 fatty acid. Description The present disclosure provides minimally invasive methods for detecting and / or quantifying proteins or nucleic acids in canine skin samples, especially with the aim of determining the likelihood of occurrence of, or the occurrence of, a disorder or a disease, including a skin disorder or disease, especially a skin inflammatory disorder such as for example atopic dermatitis. Unexpectedly, it has been found by the applicant that reproducible qualification and / or quantitation of proteins and nucleic acids contained in a canine skin sample can be made by using a method wherein the canine skin sample is collected by applying an adhesive support on a skin target area, whereby skin material is transferred to the surface of the said adhesive support, which transferred skin material can be then analysed for the presence and / or the content of proteins and / or nucleic acids contained therein. The method of collecting skin material by applying an adhesive support on a skin target area is known per se in the art and can also be termed “tape stripping”. According to the applicant’s knowledge, the said technique of tape stripping with the aim of analysing protein and / or nucleic acid content of a canine skin sample, and even less of protein and / or nucleic acid biomarkers content analysis of a canine skin sample, has never been disclosed nor suggested in the art. The present disclosure relates to a method for detecting or measuring the content of one or more selected protein biomarkers and / or one or more selected nucleic acid biomarkers in a canine skin sample, including the steps of: a) applying an adhesive tape to an exposed target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, and b) detecting the presence of, and / or measuring the content of, the said one or more selected protein biomarker and / or one or more nucleic acid biomarkers in the said epidermal sample obtained at step a). The present disclosure relates to a method for detecting or measuring the content of one or more selected protein biomarkers in a canine skin sample, including the steps of : a) applying an adhesive tape to an exposed target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, and b) detecting the presence of, and / or measuring the content of, the said one or more selected protein biomarker in the said epidermal sample obtained at step a). The present disclosure relates to a method for detecting or measuring the content of one or more selected nucleic acid biomarkers in a canine skin sample, including the steps of: a) applying an adhesive tape to an exposed target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, and b) detecting the presence of, and / or measuring the content of, the said one or more nucleic acid biomarkers in the said epidermal sample obtained at step a). The present disclosure relates to a method for detecting or measuring the content of one or more selected protein biomarkers and / or one or more selected nucleic acid biomarkers in a canine skin sample, including the steps of : a) providing an adhesive tape onto which a canine epidermal sample adhering to the adhesive tape has been previously collected, and b) detecting the presence of, and or measuring the content of, the said one or more selected protein biomarker and / or one or more nucleic acid biomarker in the said epidermal sample. The present disclosure relates to a method for detecting or measuring the content of one or more selected protein biomarkers in a canine skin sample, including the steps of : a) providing an adhesive tape onto which a canine epidermal sample adhering to the adhesive tape has been previously collected, and b) detecting the presence of, and or measuring the content of, the said one or more selected protein biomarker in the said epidermal sample. The present disclosure relates to a method for detecting or measuring the content of one or more selected nucleic acid biomarkers in a canine skin sample, including the steps of: a) providing an adhesive tape onto which a canine epidermal sample adhering to the adhesive tape has been previously collected, and b) detecting the presence of, and or measuring the content of, the said one or more selected nucleic acid biomarker in the said epidermal sample. According to the methods above, the said nucleic acid biomarkers most preferably consist of mRNA or miRNA biomarkers. By definition, protein biomarkers and nucleic acid biomarkers herein are canine biomarkers. In some embodiments of the method, the one or more selected protein biomarkers are indicative of a physiological state of the tested canine, which encompasses a physiological state of the skin of the tested canine. Thus, according to these most preferred embodiments, the said one or more selected protein biomarkers can consist of one or more protein biomarkers indicative of a physiological state of the tested canine, especially biomarkers indicative of a physiological state of the skin of the tested canine. In some embodiments of the method, the one or more selected nucleic acid biomarkers (e.g. mRNAs or miRNAs) are indicative of a physiological state of the tested canine, which encompasses a physiological state of the skin of the tested canine. Thus, according to these most preferred embodiments, the said one or more selected nucleic acid biomarkers consist of one or more nucleic acid biomarkers indicative of a physiological state of the tested canine, especially biomarkers indicative of a physiological state of the skin of the tested canine. The examples herein show an illustrative validation of such a canine skin sampling method in canine animals subject to a sensitization inducing an inflammatory reaction, and more precisely inducing an inflammatory reaction associated with an inflammatory immune response, mimicking notably the occurrence of sensitization in canine atopic dermatitis. In the examples herein, it is shown that, in these sensitized canine animals, both protein and nucleic acid biomarkers indicative of a Th2-type immunological response are increased. More precisely, it is shown herein that quantifying proteins contained in a skin sample collected by tape stripping from a canine, in which a skin inflammation has been artificially provoked by sensitization to an allergen substance, can allow to determine a significant increased content in interleukin-4 (IL-4), interleukin-13 (IL-13), interleukin-25 (IL-25), interleukin-33 (IL-33), and tumour necrosis factor alpha (TNF- ^), especially at the site of sensitization, as compared with a control skin site of the same animal that has not been sensitized. The increased combination of markers, especially IL-4 and IL-13, and the absence of increase of gamma interferon (IFN- ^) actually denotes a Th2-driven inflammatory response rather than a Th1, the presence of which, and the level of which, is shown herein to be determined in a canine skin sample. When used herein, the name of a biomarker, e.g. interleukin-4 (IL-4), intends to mean either the protein biomarker, e.g. the IL-4 protein, or the protein-encoding nucleic acid, e.g. the IL-4-encoding mRNA. Concerning other nucleic acid biomarkers, especially miRNAs biomarkers of canine atopic dermatitis, these can be chosen, as non-limitative example, among miR-203 and miR- 483. These miRNAs are described notably by Koury et al. (2019, PlosOne, Vol. 14 (6) : e0128670). It is further shown an increased expression level of the corresponding genes encoding the said protein biomarkers having an increased skin content, as confirmed by the results of mRNA differential expression. The applicant’ findings are all the more surprising that canine skin is substantially distinct from human skin, notably regarding its lower thickness, which lower thickness decreases the probability that nucleic acids and proteins be appropriately retained in an undegraded form within the canine skin. Further, there is no evidence in the art that the cells attached to the hair follicles on canine skin, to their follicular sheaths and to the follicular annexes have the same cytokinetic and / or chemokinetic synthesis and therefore nucleic expression as the keratinocytes of the human skin. Moreover, given the higher density of hair on canine skin, there is much less skin per collected surface, therefore proportionally less chances that the concentration of cytokines and / or chemokines and nucleic acids would be detectable on canine skin, in particular detectable on adhesive tape. At step a), the selected target area is first delicately clipped, or shaved, so as to expose the epidermis at the skin target area, onto which an adhesive tape will be applied. The selected area is gently clipped, or shaved, so as to avoid wounds, cuts, abrasions or erosion at the selected skin target area that has been clipped, or shaved. In a particular embodiment, the selected target area can be a lesion area of the skin. In particular, the selected target area can be an area of the skin that has been lesioned by a skin disorder or disease, especially by a skin inflammatory disorder such as for example atopic dermatitis. In another particular embodiment, the selected target area is not a lesion area of the skin. This can in particular be the case when the method described here is used as a preventive measure. At step a), the exposed skin target area can preferably be a skin area in which, after shearing, or shaving, the stratum corneum has previously been removed, so as to expose the underlying skin layer(s), especially the underlying stratum granulosum skin layer. This means that, according to the said embodiments, the said adhesive tape is applied at step a) on the surface of the stratum granulosum. In some embodiments, removing the stratum corneum can be performed by gentle successive applications of an adhesive tape on the skin area until exposing the skin layer(s) underlying the stratum corneum, especially until exposing the underlying stratum granulosum skin layer, resulting in obtaining the desired skin target area. Illustratively, exposing a skin target area can be performed by applying an adhesive tape successive times on a selected skin area, or by applying successive adhesive tapes on the selected skin area, until the skin layers underlying the stratum corneum is (are) exposed, most preferably until the underlying stratum granulosum is exposed. Illustratively, in embodiments wherein the stratum corneum is removed by using an adhesive tape, the adhesive tape is typically applied on the selected skin target area from 3 to 50 times, such as 5 to 30 times. The same adhesive tape can be applied the desired number of times and / or a plurality of adhesive tapes can be used. At step a), the epidermal sample which is collected is thus a canine skin material sample belonging to the epidermis layer(s) devoid of, or substantially devoid of, material originating from the stratum corneum layer. Most preferably, most of the said epidermal sample originates from the stratum granulosum epidermal layer. Step a) can be performed by using known skin adhesive tapes, such as non-polar, pliable, adhesive tapes, such as for example pliable tapes with rubber adhesive. For example, skin adhesive tapes can be selected among D-Squame® (polyacrylate ester adhesives; CuDerm; Dallas Tex.), Durapor, Sebutape™ (acrylic polymer films; CuDerm; Dallas, Tex.), Tegaderm™, Duct tape (333 Duct Tape, Nashua tape products), Scotch® Tape (3M Scotch 810, St. Paul, Minn.), Diamond™ (The Sellotape Company; Eindhoven, the Netherlands), Sentega™ (polypropylene tape, Sentega Eiketten BV, Utrecht, The Netherlands) may be used. The adhesive tape can be selected among any of the commonly used pressure- sensitive-type adhesives or those which solidify quickly upon skin content (such as cynaoacylates). The adhesive tape can be on flexible or solid backings to make sampling easier. At step a), the same strip of tape can be repeatedly applied to, and removed from, the target skin area. In other illustrative embodiments, a plurality of fresh pieces of adhesive tape is sequentially applied to the same target skin area. The individual tape strips used to sample a skin target area can then be combined into one extraction vessel for further processing, such as protein extraction or nucleic acid extraction, most preferably for mRNA and miRNA extraction. In some embodiments, the said collected epidermal sample which adheres to the adhesive tape can be removed, at least partly, from the tape whereby an epidermal sample is provided for further use at step b) of the method. In these embodiments, step a) can include the steps of: a1) applying an adhesive tape to an exposed skin target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, and a2) removing the said collected epidermal sample which adheres to the adhesive tape, whereby an epidermal sample is provided for its analysis at step b). At step a2), the epidermal sample can be removed according to methods well known in the art. Step a2) can be commonly performed by extraction of the collected material, such as by performing a extraction with an appropriate extraction buffer. At step a2), proteins can be extracted from the epidermal sample adhered to the adhesive tape bay any known method, such as by using a known buffer of water and ethanol, for further analysis at step b). At step a2), nucleic acids, especially for mRNAs and / or miRNAs, these RNAs can be extracted from the adhesive tape through a procedure that permits a direct qualitative and quantitative assessment of nucleic acid biomarkers, i.e. mRNAs and miRNAs biomarkers. Commercial kits can, be used such as the “RNeasy” kit RNA extraction kit and “Sensiscript Reverse Transcriptase” kit marketed by Quiagen company (Valebcia, CA, USA), PCR primers and probes (TaqMan ^ Pre-Developed Assay Reagents and TaqMan ^ Universal Master Mix, which includes all buffers and enzymes necessary for the amplification of the target nucleic acid biomarkers and then fluorescent detection of specific cDNAs (Applied Biosystems, Foster City, CA, USA). At step b) detecting the presence of, or quantifying, the said one or more selected protein biomarkers can be performed according to any method known in the art. In some embodiments, detection and / or quantitation of the said one or more selected protein biomarkers can be performed by an immunological method by using antibodies directed to the protein to be detected and / or quantified, such as an ELISA method as disclosed in the examples. At step b) detecting the presence of, or quantifying, the said one or more selected nucleic acid biomarkers, especially mRNAs or miRNAs, can be performed according to any method known in the art. Typically, detection and / or quantitation of the said one or more selected nucleic acid biomarkers can be performed by amplification of a target nucleic acid, preferably of a target mRNA or miRNA, after performing a retrotranscription of the mRNA or of the miRNA when necessary, and then detection and / or quantitation of the amplified nucleic acid, as it is shown in the examples herein, for example by using appropriately designed nucleic acid probes, which encompasses labelled nucleic acid probes. The amplification of nucleic acid molecules can be carried out in vitro by biochemical processes known to those of skill in the art. The amplification agent can be any compound or system that will function to accomplish the synthesis of primer extension products, including enzymes. It will be recognized that various amplification methodologies can be utilized to increase the copy number of a target nucleic acid in the nucleic acid skin samples obtained using the methods provided herein, before and after detection. Suitable enzymes for this purpose include, for example, E. coli DNA polymerase I, Taq polymerase, Klenow fragment of E. coli DNA polymerase I, T4 DNA polymerase, other available DNA polymerases, T4 or T7 RNA polymerase, polymerase muteins, reverse transcriptase, ligase, and other enzymes, including heat-stable enzymes (i.e., those enzymes that perform primer extension after being subjected to temperatures sufficiently elevated to cause denaturation or those using an RNA polymerase promoter to make aRNA from a DNA template, i.e. linearly amplified aRNA). One method of in vitro amplification, which can be used according to this disclosure, is the polymerase chain reaction (PCR) described in U.S. Pat. Nos.4,683,202 and 4,683,195. In some embodiments of step a) of the method, it is applied a first adhesive tape, or a plurality of “first adhesive tapes” that will be used at step a) for detecting and / or quantifying one or more selected protein biomarkers and it is applied a second adhesive tape, or a plurality of “second adhesive tapes” that will be used for detecting and / or quantifying one or more selected nucleic acid biomarkers, such as one or more selected mRNA or miRNA, irrespective of the order in which the said first and second adhesive tapes are applied. In some embodiments, the said one or more selected protein and / or nucleic acid canine biomarkers are indicative of a canine immunological state. Protein and / or nucleic acid canine biomarkers indicative of a canine immunological state can encompass (i) those protein and / or nucleic acid biomarkers that are indicative of an inflammatory response, (ii) those protein and / or nucleic acid biomarkers that are indicative of a cutaneous barrier alteration , (iii) those protein and / or nucleic acid biomarkers that are indicative of a Th2 immune response, (iv) those protein and / or nucleic acid biomarkers that are indicative of a Th1 immune response and (v) those protein and / or nucleic acid biomarkers that are indicative of a pruritus. In some embodiments, the said one or more selected protein and / or nucleic acid canine biomarkers are indicative of a canine inflammatory response. The canine biomarkers indicative of an inflammatory response can be selected, as non-limitative examples, among the following protein or nucleic acid biomarkers: C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin-1 beta (IL-1 ^), interleukin-6 (IL-6), interleukin-10 (IL-10), myeloperoxidase (MPO), matrix metalloproteinases (MMPs), adiponectine, monocyte chemoattractant protein 1 (MCP-1), and CD40 ligand. An inflammatory response can be determined when the content of the epidermal sample in at least one of inflammatory biomarkers, preferably two or more of the inflammatory biomarkers, specified above is increased. In some embodiments, the one or more selected protein and / or nucleic acid canine biomarkers can be canine biomarkers indicative of a canine Th2 immune response. The canine biomarkers indicative of a Th2 response can be selected among the following protein or nucleic acid biomarkers: interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-9 (IL-9), interleukin-10 (IL-10), interleukin-13 (IL-13), interleukin-17 (IL-17), interleukin-25 (IL-25), and interleukin-33 (IL-33), and especially among interleukin-4 (IL- 4), interleukin-5 (IL-5), and interleukin-13 (IL-13). A Th2 response can be determined when content of the epidermal sample in at least one, in particular in two or more of the Th2 biomarkers specified above is increased. Alternatively, a Th2 response can be determined when content of the epidermal sample in at least one Th2 biomarker is increased and when content in at least one other biomarker is decreased. In some embodiments, the one or more selected protein and / or nucleic acid canine biomarkers are canine biomarkers indicative of a canine Th1 immune response. The canine biomarkers indicative of a Th1 response can be selected among the following protein or nucleic acid biomarkers : gamma interferon (IFN- ^), interleukin-2 (IL- 2), tumor necrosis factor alpha (TNF- ^), interleukin-12 (IL-12), interleukin-1 beta (IL-1 ^), interleukin-18 (IL-18), interleukin-27 (IL-27), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-bet (T-box transcription factor), and especially IFN- ^ and IL-2. A Th1 response can be determined when content of the epidermal sample in at least one, in particular in two or more of the Th1 biomarkers specified above is increased. Alternatively, a Th1 response can be determined when content of the epidermal sample in at least one Th1 biomarker increases and when content in at least one other biomarker is decreased. In some embodiments, the one or more selected protein and / or nucleic acid canine biomarkers can be canine biomarkers indicative of a canine pruritus. The canine biomarkers indicative of a pruritus can be selected among the following protein or nucleic acid biomarkers: gamma interferon (IFN- ^), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL-31), interleukin 33 (IL-33), C-reactive protein (CRP), matrix metalloproteinases, substance P, eosinophil cationic protein (ECP) and thymic stromal lymphopoietin (TSLP), IFN- ^, IL-2, IL-31 and TSLP, in particular can be IL-2. A pruritus can be determined when content of the epidermal sample in at least one, preferably two or more of the pruritus biomarkers specified above is increased. In some embodiments, the one or more selected protein and / or nucleic acid canine biomarkers can be indicative of a canine atopic dermatitis. The present disclosure further relates to determine the occurrence of, or the likelihood of occurrence of an atopic dermatitis in a canine including the steps of: a) providing an epidermal sample previously collected from an adhesive tape to which the said sample adhered, b) measuring the content of two or more selected protein biomarkers and / or two or more nucleic acid biomarkers in the epidermal sample obtained at step a), wherein the said biomarkers are selected among interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL- 31), interleukin-33 (IL-33), tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^), and c) determining the occurrence of, or the likelihood of occurrence of, a canine atopic dermatitis in the said canine wherein the content of the selected biomarkers measured at step b) is increased as compared to the content of the same biomarkers of a canine which is not affected with a skin inflammation, most preferably as compared to the content of the same biomarkers of a canine which is not affected with an atopic dermatitis. In some embodiments, the one or more selected protein and / or nucleic acid canine biomarkers can be chosen among the following protein or nucleic acid biomarkers: proteins present in the epidermis. In some embodiments, the protein present in the epidermis can be selected among: a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL- 13), interleukin-25 (IL-25), interleukin-31 (IL-31) and interleukin-33 (IL-33); b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^); c) thymic stromal lymphopoietin (TSLP); and / or d) at least one protein selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. In some embodiments, protein present in the epidermis can be selected among interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), and interleukin-33 (IL-33). In some embodiments, the protein present in the epidermis comprises one or more protein selected from the group consisting of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), interleukin-33 (IL- 33), and a combination thereof. In some embodiments, the protein present in the epidermis comprises interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin- 31 (IL-31), and interleukin-33 (IL-33). In some embodiments, the protein present in the epidermis further comprises at least one protein selected from the group consisting of IL-1- 1 ^, IL-13, TNF- ^ IFN- ^, TSLP, and a combination thereof. In some embodiments, the protein present in the epidermis further comprises at least one protein selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2- hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. The present disclosure further pertains to a method of determining the presence of a cutaneous disorder state in a canine skin including the steps of: a) applying an adhesive tape to an exposed skin target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, b) detecting a statistically significantly different level of one or more protein and / or one or more nucleic acid biomarkers in the said epidermal sample, c) determining the presence of a cutaneous disorder when a statistically significantly different level of one or more of the said biomarkers is measured at step b). A "statistically significantly different level of a protein", as used herein, typically refers to a quantity of a specific protein in a biological sample (here in the skin tissue, and more precisely in a canine epidermis devoid of the stratum corneum layer) that deviates significantly from what is considered normal or expected for a particular canine individual or canine population. This abnormality can be indicative of various underlying conditions, diseases, or physiological changes. In some embodiments of the above method, the said protein and / or nucleic acid biomarkers are selected from: a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin- 10 (IL-10), interleukin-13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL-31) and interleukin-33 (IL-33); b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^); c) thymic stromal lymphopoietin (TSLP); and d) at least one protein and / or nucleic acid biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. In some embodiments, the said protein and / or nucleic acid biomarkers can be selected among interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), and interleukin-33 (IL-33). In some embodiments, the said protein and / or nucleic acid biomarkers comprise one or more protein and / or nucleic acid biomarker selected from the group consisting of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), interleukin-33 (IL-33), and a combination thereof. In some embodiments, the said protein and / or nucleic acid biomarkers comprise interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), and interleukin-33 (IL-33). In some embodiments, the said protein and / or nucleic acid biomarkers further comprise at least one protein and / or nucleic acid biomarker selected from the group consisting of IL-1-1 ^, IL-13, TNF- ^ IFN- ^, TSLP, and a combination thereof. In some embodiments, the said protein and / or nucleic acid biomarkers further comprise at least one protein and / or nucleic acid biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. In some embodiments of the above method the said cutaneous disorder is an inflammatory disorder, preferentially selected from canine atopic dermatitis, pyoderma, contact dermatitis, folliculitis, acne, seborrheic dermatitis, panniculitis, cellulitis, lick granuloma (acral lick dermatitis, histiocytoma, eosinophilic granuloma complex) nasal solar dermatitis (collie nose), interdigital cysts and furunculosis, ichtyosis, dermodicosis (dermodectic mange), ringworm (dermatophytosis) and vasculitis. In some embodiments of the above method the said cutaneous disorder is a non- inflammatory disorder, preferentially selected from alopecia aerate, colordilution alopecia, pattern baldness, congenital hypotrichosis, hyperketatosis, sebaceous adenitis, follicular dysplasia, dermoid sinus, X-linked ichtyosis, cyclic follicular dysplasia, nasal planum hyperkeratosis, hereditary footpad hyperkeratosis, primary seborrhea, vitamin A-responsive dermatosis, cutaneous mastocytosis, hypothyroidism-associated skin changes and canine epidermolysis bullosa. The present disclosure further relates to a method for the diagnosis of an atopic dermatitis state in a canine skin including the steps of: a) applying an adhesive tape to an exposed skin target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, b) detecting a statistically significantly different level of one or more selected protein and / or nucleic acid canine biomarkers in the said epidermal sample, in particular wherein the selected protein and / or nucleic acid biomarkers are chosen among interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL- 13), interleukin-25 (IL-25), interleukin-31 (IL-31), interleukin-33 (IL-33), tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^), and c) determining the presence of an atopic dermatitis state when a statistically significantly different level of one or more of the said protein and / or nucleic acid canine biomarkers is measured at step b). In some embodiments of the above method, the said protein and / or nucleic acid canine biomarkers can be selected from: a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL-31) and interleukin-33 (IL-33); b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^); c) thymic stromal lymphopoietin (TSLP); and d) at least one protein and / or nucleic acid canine biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. In some embodiments, the said protein and / or nucleic acid canine biomarkers can be selected among interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), and interleukin-33 (IL-33). In some embodiments, the said protein and / or nucleic acid canine biomarkers comprise one or more protein and / or nucleic acid canine biomarker selected from the group consisting of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), interleukin-33 (IL-33), and a combination thereof. In some embodiments, the said protein and / or nucleic acid canine biomarkers comprise interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), and interleukin-33 (IL-33). In some embodiments, the said protein and / or nucleic acid canine biomarkers further comprise at least one protein and / or nucleic acid canine biomarker selected from the group consisting of IL-1-1 ^, IL-13, TNF- ^ IFN- ^, TSLP, and a combination thereof. In some embodiments, the said protein and / or nucleic acid canine biomarkers further comprise at least one protein and / or nucleic acid canine biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. The present disclosure also concerns a method of determining the beneficial effect of a pharmaceutical agent and / or of a selected diet regimen in a canine affected with an atopic dermatitis including the steps of: a) applying an adhesive tape to an exposed skin target area of the said canine, whereby an epidermal sample adhering to the adhesive tape is collected, b) measuring the level of one or more selected protein and / or nucleic acid canine biomarker in the said epidermal sample collected at step b), c) subjecting the said canine to a treatment with a pharmaceutical agent and / or with a selected diet regimen, d) applying an adhesive tape to an exposed skin target area of the said canine, whereby an epidermal sample adhering to the adhesive tape is collected, e) detecting, and / or measuring the level of, one or more selected protein and / or nucleic acid canine biomarker in the said epidermal sample collected at step d), f) determining a beneficial effect of the said pharmaceutical agent and / or the said diet regimen when an increase and / or a decrease in the level of one or more of the biomarkers is measured at step e) when compared with the level of the same selected biomarker that was measured at step b). In some embodiments, the above method, steep a) (and step d)) can include: a1) (and d1) applying an adhesive tape from about 1 to about 50 times, preferentially from about 10 to about 30 times, on an exposed target area of the skin of said canine to remove the superficial layer of the skin, most preferably to remove the stratum corneum thereof, and a2) (and d2) applying an adhesive tape, distinct from the adhesive tape of step a1), to an exposed skin target area of the said canine, whereby an epidermal sample adhering to the adhesive tape is collected. In some embodiments of the above method, in each of steps a) and d), the adhesive tape is applied at a constant pressure. According to some embodiments of the above method, the said protein and / or nucleic acid canine biomarkers can be selected from: a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL- 4), interleukin-10 (IL-10), interleukin-13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL- 31) and interleukin-33 (IL-33); b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^); c) thymic stromal lymphopoietin (TSLP); and d) at least one protein and / or nucleic acid canine biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. In some embodiments, the said protein and / or nucleic acid canine biomarkers can be selected among interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), and interleukin-33 (IL-33). In some embodiments, the said protein and / or nucleic acid canine biomarkers comprise one or more protein and / or nucleic acid canine biomarker selected from the group consisting of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), interleukin-33 (IL-33), and a combination thereof. In some embodiments, the said protein and / or nucleic acid canine biomarkers comprise interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), and interleukin-33 (IL-33). In some embodiments, the said protein and / or nucleic acid canine biomarkers further comprise at least one protein and / or nucleic acid canine biomarker selected from the group consisting of IL-1-1 ^, IL-13, TNF- ^ IFN- ^, TSLP, and a combination thereof. In some embodiments, the said protein and / or nucleic acid canine biomarkers further comprise at least one protein and / or nucleic acid canine biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof. In some embodiments of the above method for determining the beneficial effect of a pharmaceutical agent and / or of a selected diet regimen in a canine affected with an atopic dermatitis, step c) consists of subjecting the said canine to a treatment with a pharmaceutical agent. Pharmaceutical agents can be selected among antihistamines, corticosteroids, cyclosporine, oclacitinib, lokivetmab and immunotherapy through gradual exposure to small amounts of allergen. In some other embodiments of the above method for determining the beneficial effect of a pharmaceutical agent and / or of a selected diet regimen in a canine affected with an atopic dermatitis, the diet regimen can be selected among diet containing hydrolyzed proteins, grain-free diet, omega-3 supplemented diet, antioxidant-rich diet, panthotenate- supplemented diet, choline-supplemented diet, choline-supplemented diet, nicotinamide- supplemented diet, histidine-supplemented diet, zinc-supplemented diet, copper- supplemented diet, flavonoids-supplemented diet, terpenoids-supplemented diet and inositol-supplemented diet. In all the methods of the present disclosure, detecting the presence of and / or measuring the content of, a selected protein biomarker at step b) can be performed by an immunological method. In all the methods of the present disclosure, the one or more selected nucleic acid biomarkers can be selected from mRNA and miRNA. In all the methods of the present disclosure, detecting the presence of and / or measuring the content of, a selected mRNA or miRNA biomarker at step b) can be performed by a nucleic acid amplification method. The present disclosure further concerns a kit of parts for detecting and or measuring protein and / or nucleic acid biomarkers in a canine epidermal sample, including one or more adhesive tapes for tape stripping skin according to the present description. The present disclosure further concerns a kit of parts for detecting and / or measuring protein and / or nucleic acid canine biomarkers in a canine epidermal sample, including: a) one or more adhesive tapes for tape stripping skin according to the present description, b) a reagent for collecting an epidermal sample adhered to a surface of an adhesive tape, c) reagents for detecting and / or quantifying one or more protein biomarkers, and / or d) reagents for detecting and / or quantifying one or more nucleic acids, in particular for detecting and / or quantifying one or more mRNAs or miRNAs, e) optionally, recommendations for using the kit of parts. In embodiments wherein the said kit includes reagents for detecting and / or quantifying one or more protein biomarkers, the said kit can include one or more biomarker(s)-directed antibodies and optionally means for detecting the binding of the one or more biomarker(s)-directed antibodies to their respective target proteins in the epidermal sample that has initially adhered to the adhesive tape. In embodiments wherein the said kit includes reagents for detecting and / or quantifying one or more nucleic acid biomarkers, most preferably for detecting and / or quantifying one or more mRNA or miRNA biomarkers, the said kit can include as reagents RNA extraction reagents, reverse transcriptase, DNA polymerase and optionally primers and probes for mRNA or miRNA biomarkers, whose abnormal expression is correlated with a skin disease or pathological skin state. Furthermore, the kit can include primers and probes for control genes, such as housekeeping genes. The primers and probes for control genes can be used, for example, in normalisation calculations. The kits can also include instructions for performing tape strippings as well as for analysing gene expression using normalisation calculations. In some embodiments of the said kit, it can include a probe that binds to a portion of a given nucleic acid biomarker, most preferably of a given mRNA or miRNA biomarker, In still further embodiments, the kit can include a microarray that contains one or more nucleic acid probes that can specifically hybridize with an amplification product of a selected nucleic acid biomarker, most preferably with a mRNA or a miRNA biomarker according to the present disclosure . In some embodiments, many reagents may be provided in a kit of the invention, only some of which should be used together in a particular reaction or procedure. For example, multiple primers may be provided, only two of which are needed for a particular application. The present disclosure is further illustrated by, without in anyway being limited to, the examples below. EXAMPLES This disclosure can be further illustrated by the following examples of particular embodiments thereof, although it will be understood that these examples are included merely for purposes of illustration and are not intended to limit the scope of the disclosure. Example 1 : Determining the occurrence of an atopic dermatitis in canine A. Material & Methods A.1. Canine Protocol Eight healthy beagle dogs were epicutaneously sensitized to Dermatophagoides farinae extract after tape stripping, twice a week for 49 days. A control site received only the vehicle. Adhesive tape strips D-Squame® (DS 100, Monaderm, France) were applied on skin with a standardized pressure (225 g.cm−2) by using DSquame® pressure instrument (DS500, Monaderm, France) A.2. ELISA Assays The commercial ELISA kits used in the assays are listed in Table 1 at the end of the description. These assays employ the quantitative sandwich enzyme immunoassay technique. A monoclonal antibody specific for the specified cytokine has been pre-coated onto a microplate. Standards, control, and samples are pipetted into the wells and any cytokine present is bound by the immobilized antibody. After washing away any unbound substances, a biotinylated mouse monoclonal antibody specific for the tested cytokine is added to the wells. Following a wash to remove any unbound antibody, streptavidin conjugated to HRP is added to the wells. Followed by a wash to remove any unbound streptavidin-HRP, a substrate solution is added to the wells. The enzyme reaction yields a blue product that turns yellow when the Stop Solution is added. The intensity of the color measured is in proportion to the amount of cytokine bound in the initial step. The sample values are then read from a standard curve. A.3. Transcriptomic assays Total RNA was extracted by the promoter and deep sequencing (stranded protocol, paired-end 2x150bp) was performed on these samples. This document reports the quality controls, preprocessing and statistical analyses performed on this dataset. RNAsamples were quantified using Qubit4.0 Fluorometer (LifeTechnologies, Carlsbad, CA,USA )and RNA integrity was checked with RNA Kit on Agilent 5600 Fragment Analyzer (Agilent Technologies, Palo Alto, CA, USA). The RNA sequencing library was prepared using the NEBNext Ultra II RNA Library Prep Kit for Illumina using manufacturer’s instructions (New England Biolabs, Ipswich, MA, USA). Briefly, mRNAs were initially enriched with Oligod(T) beads. Enriched mRNAs were fragmented for 15 minutes at 94 °C. First strand and second strand cDNA were subsequently synthesized. cDNA fragments were end repaired and adenylated at 3’ends, and universal adapters were ligated to cDNA fragments, followed by index addition and library enrichment by PCR with limited cycles. Sequencing libraries were validated using DNA Kit on the Agilent 5600 Fragment Analyzer (Agilent Technologies, Palo Alto, CA, USA), and quantified by using Qubit 4.0 Fluorometer (Invitrogen, Carlsbad, CA). The sequencing libraries were multiplexed and clustered on the flowcell. After clustering, the flowcell was loaded on the Illumina NovaSeq 6000 instrument according to manufacturer’s instructions. The samples were sequenced using a 2x150 Pair-End (PE) configuration. Image analysis and base calling were conducted by the NovaSeq Control Software v1.6 on the NovaSeq instrument. Raw sequence data (.bcl files) generated from Illumina NovaSeq was converted into fastq files and de-multiplexed using Illumina bcl2fastq program version 2.20. One mismatch was allowed for index sequence identification. A.4. Correlation between ELISA and transcriptomics assay results The goal was to study the effect of sensitization by an antigen on dog skins and compare the ELISA data with the transcriptomics data. Elisa data were generated as disclosed in §A.2. above. Transcriptomics data were generated as disclosed in §A.3. above. Nine cytokines (IFNG (=IFN- ^), IL-10, IL-13, IL-1B, IL-25, IL-33, IL-4 ; TNF and TSLP) were measured. Their names were used to identify the corresponding ENSEMBL IDs, listed in Table 2a hereunder. ENEMBL v105 does not contain an IL-25 gene for the reference dog assembly used for the transcriptomic analysis. Querying the NCBI for dog IL-25 returned and entry which corresponded to another ENSEMBL gene with symbol CMTM5. This ENEMBL id was therefore used for IL-25. With the original filtering procedure, the transcripts coding for cytokines IFNG, IL- 25 / CM5, IL-33 and IL-4 were considered of a low expression and were filtered from the transcriptomics dataset. They were recovered for the present analysis. A.5. Correlation between genes or proteins and clinical response of dogs, and / or predefined cytokines The goal was to study the effect of sensitization by an antigen on dog skins and compare the clinical response with the transcriptomics data. Transcriptomics data were generated as disclosed in §A.3. above. The correlation of 19 proteins with clinical response (CCL17, CCL20, CCL22, CCL5, CD2, CD3E, ELOVL3, FA2H, FCER1A, ICOS, IL13, IL17RB, IL1B, IL1RL2, IL22, IL36B, IVL, RORA, TNFRSF4) were evaluated. Their names were used to identify the corresponding ENSEMBL IDs, listed in Table 2b hereunder. A first analysis is provided considering Spearman’s correlation coefficients for each of the transcriptomics data and the clinical responses. Then for each ELISA protein, heatmaps were created for the 100 genes with highest Pearson’s correlation. The ELISA signal data was first transformed using the formula “log2(1+signal)” (IL1B was removed since its signal was flat). Only genes with at least a 2- fold change transcriptomic amplitude were considered. The same process was applied to the transcriptomic signal of CCL17, CCL5 and CCL20. B. Results B.1. Correlation between ELISA and transcriptomics assay results The results of the presence and content in each of the selected protein biomarkers and gene biomarkers are summarized in Table 3, localized at the end of the description. Table 3 also shows the correlation between (i) the detection and quantification of the selected protein biomarkers and (ii) the detection and quantification of the selected mRNA biomarkers. Thus, Table 3 compares, for each cytokine, the values observed by ELISA and those observed by transcriptomics (the transcriptomics values are the raw counts normalized by the sample size factors estimated by SESeq2). In Table 3, each line corresponds to a tested dog. In Table 3, each column corresponds to a selected biomarker, which is indicated at the bottom of said column. Table 3, is detailed below according to a reading from the left side to the right side of the table. A comment regarding the visual skin lesion reaction to sensitization, for each of the sensitized dogs is specified in the second column of Table 3. In each table cell containing results, (i) the left side in the upper part of the cell indicates the evolution of the level of the protein specified in the column, (ii) the right side in the upper right part of the cell indicates the evolution of the level of the mRNA encoding the protein specified in the column, wherein “-” corresponds to an absence of evolution, “+” corresponds to a small increase in the level of protein / mRNA and “++” corresponds to a strong increase in the level of protein / mRNA; and (iii) the symbol in the middle, in the lower section of each cell, indicates whether there is a correlation between the level of protein and the level of corresponding mRNA with regards to the lesion (check mark symbol), whether there is no correlation between the level of protein and the level of corresponding mRNA with regards to the lesion (cross symbol) or whether there is more or less a correlation between the level of protein and the level of corresponding mRNA with regards to the lesion (approximately equal to symbol) . At Day 49, ELISA and transcriptomic analysis were performed on these tape strips to study inflammatory cytokines and mRNA in the epidermis. ELISA showed a significant increase in the interleukin IL-4, IL-13, IL-33, IL-25, and TNF-α concentration on the sensitized site at day 49 compared with the control site (Friedman test, p<0.05). IL-4, IL-13, IL-33, IL-25, TNF-α, IFN-ɣ and TSLP concentration were significantly increased after sensitization compared with D0 (p<0.05). IL-1β and IL-10 were not detected. Differential expressed mRNAs were selected by gene expression level change (cutoff fold change ≥ 2 and statistical significance p ≤ 0.05). Two hundred and ten differentially regulated genes were identified between the sensitized and control site at day 49. The main pathways modified by these gene dysregulations were cell adhesion, immune response and cell migration, perfectly matching with the global immune reaction created in our sensitization procedure. B2: Deeper results obtained with 2 Dogs In order to consolidate the results, deeper analysis have been done. It will be presented hereinafter the results obtained with 2 dogs representatives of the population tested. B2.1: Correlation between ELISA and clinical signs The results obtained are showing a good correlation between the ELISA and the clinical signs, thus demonstrating the genes we will analyse are well correlated with dog response. Figures 1 and 2 are representing the results obtaind for TNF (Figure 1) and IL13 (Figure 2) with 2 differenst dogs, respectively dog 5 and dog 6, demonstrating that ELISA correlates with clinical reaction (dog 5 being a very good responder and dog 6 being amid responder). B2.2: the correation between ELISA (proteins) and their own genes The results obtained are demonstrating the good correlation between ELISA and mRNA for the related proteins / cytokines for the same two dogs 5 and 6. Figures 3 and 4 are representing the results obtaind for TNF (Figure 3) and IL13 (Figure 4) with the same dogs B2.3: the correlation of Th2 or Th1 other genes and dog response. The results obtained are demonstrating a good correlation between other Th2 or Th1 genes and the dog response. Figures 5 to 11 are respectvelly showing these results for the genes TNFRSF4 (Figure 5), FA2H (Figure 6), IL1B (Figure 7), IL13RA1 (Figure 8), IL13RA2 (Figure 9), IL22 (Figure 10) and IL4R (Figure 11). In conclusion, DSquame® appears as a suitable method to determine stratum corneum cytokine concentrations and mRNA mapping. mRNA analysis, despite a known individual variability, showed a correlation with the Th2 reaction created in the sensitization procedure.80 58İ BIBLIOGRAPHY 1. Clausen et al., 2020, Nature Research.10 : 21895 2. Dyjack et al., 29, J Allergy Clin Immunol, Vol.141 (4) : 1298-1309 3. Morlang et al., 2021, Vet Dermatol, Vol.32 : 331 – e92 4. Koury et al., 2019, PlosOne, Vol.14 (6) : e0128670 * * * Although the presently disclosed subject matter and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the present disclosure. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, and compositions of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the present disclosure of the presently disclosed subject matter, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the presently disclosed subject matter. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps. Various patents, patent applications, publications, product descriptions, protocols, and sequence accession numbers are cited throughout this application, this present disclosures of which are incorporated herein by reference in their entireties for all purposes.
Claims
CLAIMS 1. A method for detecting or measuring the content of one or more selected protein biomarkers and / or one or more nucleic acid biomarkers in a canine skin sample, comprising the steps of: a) applying an adhesive tape to an exposed skin target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, and b) detecting the presence of, and / or measuring the content of, the said one or more selected protein biomarker and / or one or more nucleic acid biomarker in the epidermal sample obtained at step a).
2. The method of claim 1, wherein at step b) the one or more selected protein and / or nucleic acid canine biomarkers are indicative of a canine immunological state. 3.The method of claim 1, wherein at step b) the one or more selected protein and / or nucleic acid canine biomarkers are canine biomarkers indicative of a canine inflammatory response.
4. The method of claim 1, wherein at step b) the one or more selected protein and / or nucleic acid canine biomarkers are canine biomarkers indicative of a canine Th2 immune response.
5. The method of claim 1, wherein the one or more selected protein and / or nucleic acid canine biomarkers are chosen among proteins present in the epidermis.
6. The method of claim 5, wherein the one or more selected proteins present in the epidermis are chosen among: a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL-31) and interleukin-33 (IL-33) ; b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^) ; c) thymic stromal lymphopoietin (TSLP); and / or d) one or more proteins selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H),interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL- 4R), and a combination thereof.
7. The method according to any one of claims 1 to 6, wherein detecting the presence of and / or measuring the content of, a selected protein biomarker at step b) is performed by an immunological method.
8. The method according to any one of claims 1 to 7, wherein the one or more selected nucleic acid biomarkers are selected from mRNA and miRNA.
9. The method of claim 8, wherein detecting the presence of and / or measuring the content of a selected mRNA or miRNA biomarker at step b) is performed by a nucleic acid amplification method.
10. A method of determining the presence of a cutaneous disorder state in a canine skin comprising the steps of: a) applying an adhesive tape to an exposed target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, b) detecting a statistically significantly different level of one or more protein and / or one or more nucleic acid canine biomarkers in the said epidermal sample, c) determining the presence of a cutaneous disorder when a statistically significantly different level of one or more of the said biomarkers is measured at step b).
11. The method of claim 11, wherein the said cutaneous disorder is an inflammatory disorder, preferentially selected from canine atopic dermatitis, pyoderma, contact dermatitis, folliculitis, acne, seborrheic dermatitis, panniculitis, cellulitis, lick granuloma (acral lick dermatitis, histiocytoma, eosinophilic granuloma complex) nasal solar dermatitis (collie nose), interdigital cysts and furunculosis, ichtyosis, dermodicosis (dermodectic mange), ringworm (dermatophytosis) and vasculitis.
12. The method of claim 10, wherein the said cutaneous disorder is a non-inflammatory disorder, preferentially selected from alopecia aerate, colordilution alopecia, pattern baldness, congenital hypotrichosis, hyperketatosis, sebaceous adenitis, follicular dysplasia, dermoid sinus, X-linked ichtyosis, cyclic follicular dysplasia, nasal planum hyperkeratosis, hereditary footpad hyperkeratosis, primary seborrhea, vitamin A-responsive dermatosis, cutaneous mastocytosis, hypothyroidism-associated skin changes and canine epidermolysis bullosa.
13. A method for the diagnosis of an atopic dermatitis state in a canine skin comprising the steps of: a) applying an adhesive tape to an exposed skin target area of the canine, whereby an epidermal sample adhering to the adhesive tape is collected, b) detecting statistically significantly different level of one or more protein and / or nucleic acid canine biomarkers in the said epidermal sample, c) determining the presence of an atopic dermatitis state when a statistically significantly different level of one or more of the said protein and / or nucleic acid canine biomarkers is measured at step b).
14. The method of any one of the claims 10 to 13, wherein the said protein and / or nucleic acid canine biomarkers are selected from: a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL-31) and interleukin-33 (IL-33) ; b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^); c) thymic stromal lymphopoietin (TSLP); and d) one or more protein and / or nucleic acid canine biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof.
15. A method of determining the beneficial effect of a pharmaceutical agent and / or of a selected diet regimen in a canine affected with an atopic dermatitis comprising the steps of: a) applying an adhesive tape to an exposed skin target area of the said canine, whereby an epidermal sample adhering to the adhesive tape is collected, b) measuring the level of one or more selected protein and / or nucleic acid canine biomarker in the said epidermal sample collected at step b), c) subjecting the said canine to a treatment with a pharmaceutical agent and / or with a selected diet regimen, d) applying an adhesive tape to an exposed skin target area of the said canine, whereby an epidermal sample adhering to the adhesive tape is collected, e) detecting, and / or measuring the level of, one or more selected protein and / or nucleic acid canine biomarker in the said epidermal sample collected at step d), f) determining a beneficial effect of the said pharmaceutical agent and / or the said diet regimen when an increase and / or a decrease in the level of one or more of the biomarkers is measured at step e) when compared with the level of the same selected biomarker that was measured at step b).
16. The method according to claim 15, wherein step a) and step d) comprises: a1) (and d1) applying an adhesive tape from about 1 to about 50 times, preferentially from about 10 to about 30 times, on an exposed target area of the skin of said canine to remove the superficial layer of the skin, most preferably to remove the stratum corneum thereof, and a2) (and d2) applying an adhesive tape, distinct from the adhesive tape of step a1), to an exposed skin target area of the said canine, whereby an epidermal sample adhering to the adhesive tape is collected.
17. The method of claim 15 or 16, wherein, in each of steps a) and d), the adhesive tape is applied at a constant pressure.
18. The method according to any one of claims 15 to 17, wherein said protein or nucleic acid canine biomarkers are selected from:a) interleukin-1 beta (IL-1 ^), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin- 13 (IL-13), interleukin-25 (IL-25), interleukin-31 (IL-31) and interleukin-33 (IL-33); b) tumor necrosis factor alpha (TNF- ^) and gamma interferon (IFN- ^); and c) thymic stromal lymphopoietin (TSLP); and d) one or more protein or nucleic acid canine biomarker selected from the group consisting of tumor necrosis factor superfamily member 4 (TNFRSF4), fatty acid 2-hydroxylase (FA2H), interleukin-13 receptor subunit alpha 1 (IL13RA1), interleukin-13 receptor subunit alpha 2 (IL13RA2), interleukin-22 (IL-22), interleukin-4 receptor (IL-4R), and a combination thereof.
19. The method according to any one of claims 1-18, wherein the said one or more selected protein biomarker and / or one or more nucleic acid biomarker are selected from interleukin- 4 (IL-4), interleukin-10 (IL-10), interleukin-25 (IL-25), interleukin-31 (IL-31), and interleukin-33 (IL-33).
20. Kit of parts for detecting and / or measuring protein and / or nucleic acid canine biomarkers in a canine epidermal sample, comprising: a) one or more adhesive tapes for tape stripping skin, b) a reagent for collecting an epidermal sample adhered to a surface of an adhesive tape, c) reagents for detecting and / or quantifying one or more protein biomarkers, and / or d) reagents for detecting and / or quantifying one or more nucleic acids, in particular for detecting and / or quantifying one or more mRNAs or miRNAs, e) optionally, recommendations for using the kit of parts.