Method for predicting atopic dermatitis

Abstract

Provided is a method for predicting atopic dermatitis.　The present invention provides a method for predicting the possibility of the onset of atopic dermatitis by using the expression of SCCA in an infant subject as an index.

Description

How to predict atopic dermatitis

[0001] The present invention provides a method for predicting the likelihood of developing atopic dermatitis using squamous cell carcinoma antigen (SCCA) in skin stratum corneum cells as an indicator. More specifically, the present invention relates to a method for predicting the likelihood of developing atopic dermatitis using SCCA expression in a biological sample collected from a 2-month-old infant as an indicator.

[0002] Atopic dermatitis is one of the most common skin diseases, occurring primarily during infancy, with 80% of cases occurring during infancy. It has been suggested that atopic dermatitis can be prevented by appropriate skin care during infancy (Non-Patent Document 1).

[0003] However, atopic dermatitis is generally treated after symptoms appear, and diagnosis relies solely on the doctor's visual findings. In other words, the diagnosis is made after the onset of the disease, and treatment guidelines are determined based on the doctor's diagnosis. However, once atopic dermatitis develops, it is difficult to achieve a complete cure, even if it goes into remission. Therefore, it is important to recognize the possibility of atopic dermatitis developing in infancy and take appropriate measures to maintain good skin condition during infancy.

[0004] Thus, although early recognition of atopic dermatitis is important, accurate early prediction is difficult. The onset mechanism of atopic dermatitis is unknown, but it is believed to develop primarily as a result of a combination of genetic predisposition and various environmental factors. Genetic predispositions include family history and a tendency to produce IgE antibodies, while environmental factors include temperature, humidity, clothing, bedding, detergent residue, dust, house dust, stress, an irregular lifestyle, and diet. However, it is extremely difficult to comprehensively assess these many predispositions and predict the likelihood of onset. In particular, infants and young children are unable to report symptoms themselves, making it difficult to confirm the presence or absence of such predispositions. Furthermore, atopic dermatitis worsens in a short period of time, so an indicator for early and easy prediction of the likelihood of onset is needed.

[0005] Currently, there are few established indicators for predicting the possibility of developing atopic dermatitis. For example, Patent Document 1 discloses a method for evaluating or predicting the possibility of developing atopic dermatitis using acetone in gas volatilized from the skin surface as an indicator (claims 3, 4, etc.). However, special equipment is required to collect gas volatilized from the skin surface and measure the amount of acetone. Patent Document 2 discloses a method for evaluating the possibility of developing dermatitis using the ratio of ceramide components 1 and 2 contained in a lipid sample prepared from a sample of the stratum corneum of infant skin as an indicator (claims, etc.). However, the method of Patent Document 2 is not specialized for atopic dermatitis.

[0006] The following disclosures are also available as indicators for assessing the presence or absence of atopic dermatitis or its severity. Patent Document 3 discloses a method for testing for the presence or absence of allergic diseases, including atopic dermatitis, by measuring the concentrations of SCCA1 and SCCA2 in a biological sample and calculating the ratio of these concentrations (claims 1, 8, etc.). Patent Document 4 discloses a decision-support method for classifying the severity of atopic dermatitis using the expression level of SCCA-1 in the stratum corneum cells of a subject as an indicator and using this as an indicator for deciding which treatment to apply according to each level (claim 1, etc.). Patent Document 5 discloses a method for detecting the presence or absence of infant atopic dermatitis or the degree of its progression, which includes a step of measuring the expression level of SerpinB4 protein in surface lipids of the skin collected from an infant subject (claims 1, 2, etc.). Patent Document 6 discloses a detection method for assessing the presence or absence of infantile atopic dermatitis in a subject, comprising a step of measuring the expression level of at least one gene or its expression product selected from a group of seven genes consisting of IMPDH2, ERI1, FBXW2, STK17B, TAGLN2, AMICA1, and HNRNPA1 in a biological sample collected from the subject (claim 5, etc.). Patent Document 7 discloses a method for assessing the presence or absence of infantile atopic dermatitis or the degree of its progression in skin surface lipids collected from a subject, using the TARC gene as an indicator (claims 1, 3, etc.). However, these methods are merely methods for assessing atopic dermatitis and do not predict the possibility of onset. Once onset occurs, complete cure is difficult, so it is important to be able to predict as early as possible.

[0007] Patent Document 8 discloses that SCCA in stratum corneum cells can be used as an index for predicting parakeratosis caused by atopic dermatitis. However, although Patent Document 8 demonstrates parakeratosis in adults in the examples, it does not specialize in the possibility of onset of atopic dermatitis in infants at a specific age. As mentioned above, since skin care during infancy is particularly important, it is important to predict the possibility of onset as early as possible and maintain good skin condition during infancy in advance.

[0008] Non-Patent Document 2 discloses testing serum TARC and serum SCCA2 concentrations to evaluate predisposition to atopy in children. Non-Patent Document 3 discloses that SCCA in serum collected from adults is associated with the severity and clinical type of atopic dermatitis. However, collecting serum requires medical professionals and specific equipment, and collecting the necessary samples is not easy, even more so for infants. Therefore, it would be desirable to be able to identify the possibility of developing atopic dermatitis early using samples that can be obtained from infancy using a simple and non-invasive method.

[0009] Japanese Patent Publication No. 2019-219256 Japanese Patent No. 6793543 Japanese Patent No. 5750645 Japanese Patent No. 6835479 Japanese Patent Publication No. 2022-82068 Japanese Patent Publication No. 2021-175382 Japanese Patent Publication No. 2022-49694 International Publication No. 2006 / 098523

[0010] Kenta Horimukai, et al., J Allergy Clin Immunol 2014;134:824-30 Allergy 67(8) 981-986. 2018 Allergol; Int 2018;67:124-30 Japanese Journal of Dermatology 119(8), 151-1534, 2009 Dermatology. 1993;186(1):23-31. doi: 10.1159 / 000247298.

[0011] An object of the present invention is to provide a method for predicting the possibility of the onset of atopic dermatitis, particularly in infancy.

[0012] As a result of extensive research, the present inventors have discovered that the possibility of developing atopic dermatitis in infants can be predicted by using SCCA expression as an indicator, and have completed the following inventions. [1] A method for assisting in prediction of the possibility of a subject developing atopic dermatitis by the age of three, using SCCA expression in a biological sample collected from the face of a two-month-old infant as an indicator. [2] A method for testing a biological sample collected from the face of a two-month-old infant to determine whether the subject is likely to develop atopic dermatitis by the age of three, the method comprising measuring SCCA expression in the biological sample. [3] The method according to [1] or [2], comprising a step of comparing the SCCA expression level in the biological sample with a reference value, wherein a value of SCCA expression in the biological sample higher than the reference value indicates that the subject is likely to develop atopic dermatitis by the age of three. [4] The method according to [3], wherein the reference value is a cutoff value. [5] The method according to any one of [1] to [4], wherein the biological sample is collected non-invasively by tape stripping. [6] The method according to any one of [1] to [5], wherein the SCCA is SCCA-1. [7] A kit for predicting the likelihood that a subject will develop atopic dermatitis by the age of three, comprising a medium for collecting a biological sample from the face of a two-month-old infant and a reagent for measuring SCCA expression in the biological sample collected with the medium. [8] The kit according to [7], wherein the medium is a tape to be attached to the skin of the subject, and the biological sample is collected non-invasively by tape stripping. [9] A system for predicting the possibility that a 2-month-old infant subject will develop atopic dermatitis by the age of 3 years, the system comprising: a data acquisition unit that acquires data on SCCA expression from a biological sample collected from the face of the 2-month-old infant subject; a prediction unit that refers to the data acquired by the data acquisition unit and predicts, if SCCA expression is higher than a reference value, that the 2-month-old infant subject is likely to develop atopic dermatitis by the age of 3 years; and a display unit that displays the result predicted by the prediction unit.

[0013] By employing the method of the present invention, the possibility of developing atopic dermatitis can be detected during infancy.

[0014] Figure 1 shows the mean SCCA-1 values ​​(ng / mg = SCCA amount / total protein amount) in samples collected from each test site of the subject at each measurement time point, divided by the presence or absence of atopic dermatitis by age 3 years (t-test). Figure 2 shows the mean SCORAD total values ​​in each test site of the subject at each measurement time point, divided by the presence or absence of atopic dermatitis by age 3 years (t-test). Figure 3 shows the ROC curve for SCCA-1 values ​​in samples collected from the cheeks of 2-month-old infants and the presence or absence of atopic dermatitis by age 3 years. Figure 4 shows the ROC curve for SCCA-1 values ​​in samples collected from the perioral area of ​​2-month-old infants and the presence or absence of atopic dermatitis by age 3 years.

[0015] The present inventors measured the expression levels of SCCA in biological samples collected from infants and investigated the occurrence of atopic dermatitis over a long period of time. As a result, it was found that the SCCA levels in samples collected from 2-month-old infants were highly correlated with the likelihood of future onset of atopic dermatitis.

[0016] Squamous cell carcinoma-associated antigen (SCCA) is an antigen extracted from squamous cell carcinoma cells. It is found at high blood concentrations in squamous cell carcinomas of the cervix, lung, esophagus, and skin, and is often used to diagnose squamous cell carcinoma. SCCA is also known to be upregulated in the upper layers of the epidermis in psoriasis. As mentioned above, various literature suggests a relationship between atopic dermatitis and SCCA. However, none of the literature has demonstrated that SCCA in infants aged 2 months can objectively predict the onset of atopic dermatitis in the future, more specifically, by the age of 3 years.

[0017] SCCA is encoded by two genes, SCCA-1 and SCCA-2, which are arranged in tandem on chromosome 18q21.3. The proteins encoded by these genes, SCCA-1 and SCCA-2, both have a molecular weight of approximately 45,000 and exhibit high homology, with the homology reaching 95% at the nucleic acid level. These SCCAs belong to the ovalbumin-serine protease inhibitor (ov-serpin) family. Ov-serpins have unique characteristics within the serpin superfamily. While serpins are generally secreted and function extracellularly, ov-serpins are protease inhibitors that primarily function intracellularly. The SCCA measured in the present invention may be either SCCA-1 or SCCA-2, with SCCA-1 being preferred.

[0018] Therefore, the present invention provides a method for predicting the likelihood that an infant or toddler will develop atopic dermatitis in the future, using the expression of SCCA in a biological sample collected from the subject as an indicator. The timing of "prediction" is preferably as early as possible, for reasons such as the difficulty of complete cure once the disease has developed and the importance of taking appropriate measures before or at an early stage of onset. As used herein, "prediction" refers to measuring the likelihood that a 2-month-old infant or toddler will develop atopic dermatitis by the age of 3. "By the age of 3" refers to any time point during the period from 4 months to 3 years of age, such as 4 months to 3 years, 4 months to 5 months, 8 months to 3 years, 8 months to 1 year and 6 months, 8 to 9 months, 8 months to 1 year, 9 months to 1 year, 1 year to 1 year and 6 months, or 1 year and 6 months to 3 years.

[0019] The present invention also provides a method for testing a biological sample collected from the face of a 2-month-old infant subject to determine whether the subject is likely to develop atopic dermatitis by the age of 3. The method of the present invention may comprise measuring an expression level of SCCA in the biological sample collected from the face of the 2-month-old infant subject.

[0020] Although not limited to this, the method of the present invention can predict, from a biological sample collected from the face, such as around the mouth and / or cheeks, of a 2-month-old infant or toddler subject, the possibility of the subject developing atopic dermatitis in the face, such as around the mouth and / or cheeks, or in the abdomen within the period of 4 to 5 months, or the possibility of the subject developing atopic dermatitis in the back, abdomen, or front thighs within the period of 8 months to 3 years of age, for example, at the age of 1 year and 6 months, or can be used to test whether the subject is a subject with such a possibility.

[0021] The SCCA expression assay of the present invention can be performed quantitatively or qualitatively using any method capable of measuring SCCA. Specifically, various methods are available, including immunoassays using SCCA-specific antibodies, such as enzyme-labeled ELISA, radioactive labeled RIA, immunoturbidimetry, Western blotting, latex agglutination, hemagglutination, immunochromatography, resonance plasmon resonance, SAW (surface acoustic wave) devices, and electronic device assays. Immunoassay methods include competitive assays and sandwich assays. Alternatively, the expression level of SCCA can be measured by measuring the intracellular expression level of the gene encoding it. In this case, for example, SCCA expression can be determined by measuring the amount of intracellular mRNA encoding SCCA. Extraction of mRNA and quantitative or qualitative measurement of its amount are also well known in the art and can be performed using various well-known methods, such as PCR, 3SR, NASBA, and TMA. Alternatively, SCCA expression can be qualitatively determined by in situ hybridization or by measuring its biological activity.

[0022] Although biological samples can be collected by any method, non-invasive collection by tape stripping is preferred from the perspective of simplicity. Tape stripping is a method of collecting a stratum corneum sample by applying a piece of adhesive tape to the surface of the skin, peeling it off, and allowing the stratum corneum to adhere to the peeled adhesive tape. In one embodiment, the biological sample is stratum corneum collected non-invasively by tape stripping. Tape stripping enables measurement of SCCA expression simply by collecting the stratum corneum with a single piece of tape, enabling a method for understanding the pathology of atopic dermatitis using SCCA as an indicator. A preferred method of tape stripping involves first removing sebum, dirt, etc. from the surface of the skin, lightly placing a piece of adhesive tape cut to an appropriate size (e.g., 2 x 6 cm) on the skin surface, applying uniform pressure to the entire tape to flatten it, and then peeling off the adhesive tape with uniform pressure. Methods for removing sebum, dirt, etc. from the surface of the skin include wiping with tissue paper, washing with soap, and purifying with water or ethanol. The adhesive tape may be commercially available cellophane tape, and examples thereof include Scotch Superstrength Mailing Tape (manufactured by 3M Corporation) and cellophane tape (Cellotape (registered trademark); Nichiban Co., Ltd.). SCCA-1 in a stratum corneum sample attached to adhesive tape can be isolated and extracted from the tape by immersing a piece of tape in an appropriate extraction solution, for example, Tris-buffer (pH 8.0) (0.1 M Tris-HCl, 0.14 M NaCl, 0.1% Tween-20), and extracting the stratum corneum. The site from which the biological sample is collected is preferably the face, and more preferably the area around the mouth and / or cheek.

[0023] A high SCCA expression level in a biological sample indicates that the subject is likely to develop atopic dermatitis by the age of 3. However, the SCCA expression level will vary depending on the SCCA measurement system used. Therefore, to assign a subject to an appropriate likelihood of developing atopic dermatitis according to the SCCA expression level, a reference value that can be used as a basis for judgment may be determined for the SCCA measurement system used.

[0024] Therefore, in one embodiment, the method of the present invention may include a step of comparing the expression level of SCCA in the biological sample with a reference value, and if the expression level of SCCA in the biological sample is higher than the reference value, it indicates that the subject is at risk of developing atopic dermatitis by the age of 3.

[0025] With regard to the reference value, in one embodiment, if the value of SCCA-1 or SCCA-2 in a skin stratum corneum sample collected by tape stripping from the cheek of a 2-month-old infant subject is, for example, about 1000 ng / mg or more, about 1100 ng / mg or more, about 1200 ng / mg or more, about 1300 ng / mg or more, about 1400 ng / mg or more, about 1444 ng / mg or more, or about 1500 ng / mg or more per total protein, this indicates that the subject is likely to develop atopic dermatitis by the age of 3. In one embodiment, a value of SCCA-1 or SCCA-2 per total protein in a stratum corneum sample collected by tape stripping from around the mouth of a 2-month-old infant subject of, for example, about 900 ng / mg or more, about 950 ng / mg or more, about 1000 ng / mg or more, about 1010 ng / mg or more, about 1020 ng / mg or more, about 1021 ng / mg or more, about 1030 ng / mg or more, about 1100 ng / mg or more, about 1200 ng / mg or more, or about 1300 ng / mg or more indicates that the subject is likely to develop atopic dermatitis by the age of 3.

[0026] For example, in one aspect of this embodiment, the reference value is a cutoff value for the SCCA-1 or SCCA-2 level per total protein in a stratum corneum sample collected by tape stripping from the face of a 2-month-old infant. The cutoff value can be determined by a logistic regression model using an ROC cutoff value, with the presence or absence of atopic dermatitis at age 3 as the objective variable and the SCCA expression level as the explanatory variable. In this case, a method that maximizes the Youden Index ("sensitivity - (1 - specificity)") can be used.

[0027] In one example of this aspect, if SCCA-1 expression in a stratum corneum sample collected by tape stripping from the cheek of a 2-month-old infant subject is higher than the cutoff value of 1444 ng / mg, this indicates that the subject is likely to develop atopic dermatitis by the age of 3. In another example of this aspect, if SCCA-1 expression in a stratum corneum sample collected by tape stripping from around the mouth of a 2-month-old infant subject is higher than the cutoff value of 1021 ng / mg, this indicates that the subject is likely to develop atopic dermatitis by the age of 3.

[0028] The method of the present invention uses the expression level of SCCA as an index, and therefore does not require the involvement of a doctor or medical professional. One embodiment of the present invention is a method for assisting in prediction of the possibility of developing atopic dermatitis, which does not involve a diagnosis by a doctor or medical professional.

[0029] The present invention also provides a kit for predicting the likelihood of developing atopic dermatitis. The kit of the present invention comprises a medium for collecting a biological sample from a subject and a reagent for measuring SCCA expression in the biological sample collected using the medium. If the SCCA expression in the biological sample measured using the kit is higher than the reference value, it indicates that the subject is at risk of developing atopic dermatitis by the age of three. The age of the subject from whom the biological sample is collected, the collection site, the reference value, and the time of prediction are as described above. The medium preferably includes the above-described tape for application to the subject's skin, and the biological sample is collected non-invasively by tape stripping. The reagent is not limited as long as it is used to measure SCCA expression, and examples include reagents necessary for measuring SCCA expression using the above-described method. Examples include anti-SCCA-1 monoclonal antibody, anti-SCCA-2 monoclonal antibody, anti-SCCA-1 polyclonal antibody, anti-SCCA-2 polyclonal antibody, or a reagent for measuring any of these antibodies, which are necessary for an ELISA assay to measure SCCA levels.

[0030] The present invention also provides a system for predicting the likelihood of developing atopic dermatitis, comprising: a data acquisition unit that acquires data on SCCA expression from a biological sample collected from a subject; a prediction unit that refers to the data acquired by the data acquisition unit and predicts that the subject is likely to develop atopic dermatitis if the SCCA expression is higher than a reference value; and a display unit that displays the results predicted by the prediction unit. The age, collection site, reference value, and prediction time of the subject from whom the biological sample is collected are as described above.

[0031] The present invention will be described in more detail below with reference to specific examples, although the present invention is not limited thereto.

[0032] 1. Evaluation and observation items (1) Subjects: 117 2-month-old infants (55 females, 62 males) (2) Test sites: Cheeks, perioral areas, back, abdomen, and front of thighs of the subjects (3) Measurement period: The expression level of SCCA-1 was measured over time using the method described below at 2 months, 4-5 months, 8-9 months, 1 year and 6 months, and 3 years of age, and the presence or absence of atopic dermatitis was diagnosed at each test site.

[0033] 2. Measurement of SCCA-1 Expression Levels (1) Collection and Measurement of Stratum Corneum Tapes Stratum corneum samples were collected from each test site (perioral, cheek, back, abdomen, anterior thigh; for 1 year 6 months and 3 years old, only the back, abdomen, and anterior thigh) using Cellotape (registered trademark) (2 cm x 6 cm). The obtained stratum corneum samples were immersed in a protein extract (0.1 M Tris-HCl (pH 8.0), 0.14 M NaCl, 0.1% Tween 20) and extracted using a Bioruptor. After centrifugation, the supernatant was used in the measurement method (2) below.

[0034] (2) Immunological SCCA-1 Measurement Method: Recombinant human SCCA-1 was obtained by inserting SCCA-1 cDNA into the pQE30 vector. The recombinant was purified with Ni-Agarose, then further purified by Mono Q chromatography, and used as the standard for ELISA assay. This describes the SCCA-1 measurement method. Rabbit anti-SCCA-1 polyclonal antibody (manufactured by Shiseido) was immobilized on a 96-well plate as the primary antibody. After blocking with ImmunoBlock (DS Pharma Biomedical, Osaka, Japan), 100 μl of stratum corneum extract was added to each well, and the plate was incubated for 1 hour at 37°C. Monoclonal anti-SCCA1 antibody (Santa Cruz) was used as the secondary antibody, and the reaction was carried out for 1 hour at 37°C. Then, horseradish peroxidase-conjugated anti-mouse F(ab')2 (GE Healthcare) was added, and color development was carried out using a TMB peroxidase EIA substrate kit (Bio-Rad). The reaction was carried out in 1 M H ２ SO ４ The reaction was stopped at 450 nm and measured at 450 nm.

[0035] 3. Physician's Findings Diagnosing atopic dermatitis can be difficult even for experienced physicians, much less for laypeople without medical experience. In this example, experienced physicians examined patients for atopic dermatitis at each of the above measurement periods and evaluated the severity of local skin symptoms using the Local SCORAD clinical score, which excludes subjective symptoms and rash area from the clinical score (erythema, wetting / papules, erosion / crusts, keratinocyte peeling, lichenification / prurigo, and dryness). Based on this, patients who had experienced atopic dermatitis at least once by the age of three were classified as present, and those who had not experienced atopic dermatitis were classified as absent. A t-test was used to compare the mean values ​​between two groups, a t-test followed by ANOVA was used to compare the mean values ​​between three groups, and Fisher's exact test was used to compare proportions.

[0036] Clinical scores were calculated according to the method described in Non-Patent Document 4, by summing the severity of the subject's skin symptoms (rash, erythema, infiltration / rash, exudate / crust, excoriation, lichenification, and dryness) and calculating the Local SCORAD value.

[0037] 4. Creation of ROC curves The SCCA-1 values ​​at each test site at each measurement time point and the presence or absence of onset of atopic dermatitis up to the age of 3 were plotted on a plane for each cutoff point, and an ROC curve was created by connecting the sensitivity and specificity with a line. The cutoff value was determined using a logistic regression model, with the presence or absence of onset of atopic dermatitis at the age of 3 as the objective variable and the SCCA expression value as the explanatory variable. In this case, a method was used that maximized the Youden Index ("sensitivity - (1 - specificity)")

[0038] 5. Results The results are shown in Figures 1 to 4. Figure 1 shows the SCCA-1 levels (ng / mg = SCCA amount / total protein amount) in samples collected from each test site of the subjects at each measurement time point, divided into those with and without atopic dermatitis by age 3 years. The SCCA-1 levels in samples collected from the cheek at 2 months were 787 ng / mg on average (SD 566 ng / mg, SD 102 ng / mg, lower 95%: 579 ng / mg, upper 95%: 994 ng / mg) in the group that did not develop atopic dermatitis by age 3 years, whereas the SCCA-1 levels in the group that developed atopic dermatitis by age 3 years were 1653 ng / mg on average (SD 1556 ng / mg, SD 178 ng / mg, lower 95%: 1297 ng / mg, upper 95%: 2009 ng / mg). The SCCA-1 levels in perioral samples taken at 2 months were 704 ng / mg (SD 966 ng / mg, SD 173 ng / mg, lower 95%: 349 ng / mg, upper 95%: 1058 ng / mg) in the group that did not develop atopic dermatitis by age 3 years, and 1560 ng / mg (SD 1710 ng / mg, SD 196 ng / mg, lower 95%: 1169 ng / mg, upper 95%: 1950 ng / mg) in the group that developed atopic dermatitis by age 3 years. In the SCCA-1 levels in samples taken from the cheek or around the mouth at 2 months, a significant difference was observed between the group that had developed atopic dermatitis by the age of 3 years and the group that had not, but no significant differences were observed between the groups in samples taken from other sites at 2 months or in samples taken between 4 and 9 months.

[0039] Figure 2 shows the total SCORAD scores at each test site of the subjects at each measurement time point, divided by the presence or absence of atopic dermatitis by age 3 years. At 2 months of age, no significant differences in SCORAD scores were observed between groups with or without atopic dermatitis at any test site other than the perioral area. However, as the children grew, the differences in SCORAD scores at each test site became significant between 4 months and 3 years of age. In particular, significant differences were observed between groups that developed atopic dermatitis on the face (e.g., perioral and / or cheeks) or abdomen between 4 and 5 months of age and those that did not; between groups that developed atopic dermatitis on the back or abdomen between 8 months and 3 years of age and those that did not; and between groups that developed atopic dermatitis on the front thighs at 1 year and 6 months of age and those that did not.

[0040] Figure 3 shows the ROC curve for the relationship between SCCA-1 levels in samples collected from the cheeks of 2-month-old infants and the presence or absence of atopic dermatitis by age 3 years. When the cutoff value for SCCA-1 in cheek samples was set to 1444 ng / mg (SCCA amount / total protein amount), the sensitivity was 0.4342 and the specificity was 0.9355. Figure 4 shows the ROC curve for the relationship between SCCA-1 levels in samples collected from the perioral area of ​​2-month-old infants and the presence or absence of atopic dermatitis by age 3 years. When the cutoff value for SCCA-1 in samples collected from the perioral area was set to 1021 ng / mg (SCCA amount / total protein amount), the sensitivity was 0.5263 and the specificity was 0.8387. It can be seen that subjects with high SCCA-1 expression levels in samples collected from the face, such as the cheeks or perioral area, of 2-month-old infants are more likely to develop atopic dermatitis by age 3 years.

[0041] According to the present invention, even if atopic dermatitis has not developed at 2 months, the possibility of developing atopic dermatitis by the age of 3 years can be indicated by using the expression of SCCA as an indicator.In addition, even if atopic dermatitis has developed at 2 months, it is often impossible for the child to complain about it, so by using the expression of SCCA as an indicator, guardians can know the possibility of the subject developing atopic dermatitis at an early stage.As mentioned above, it is important to provide appropriate skin care as early as possible to treat atopic dermatitis, so it is extremely advantageous to be able to predict the possibility of atopic dermatitis during infancy.

[0042] Furthermore, SCCA can be collected by a very simple and non-invasive procedure, such as tape stripping. With the development of a simple measurement kit, SCCA measurement can be performed at home, not just in a hospital or laboratory. This is extremely advantageous, especially for infants, as it allows for easy prediction of the possibility of onset at home.

[0043] By using SCCA as an indicator, the present invention makes it possible to provide a method for predicting the possibility of the onset of atopic dermatitis in infants using a simple and objective indicator.

Claims

1. A method for assisting in predicting the possibility that a subject, who is an infant at 2 months old, will develop atopic dermatitis by the age of 3, using the expression of SCCA in a biological sample collected from the face of the subject as an indicator.

2. A method for examining a biological sample collected from the face of a subject, who is an infant at 2 months old, to determine whether the subject may develop atopic dermatitis by the age of 3, the method comprising measuring the expression of SCCA in the biological sample.

3. The method according to claim 1 or 2, comprising a step of comparing the expression value of SCCA in the biological sample with a reference value, and indicating that the subject may develop atopic dermatitis by the age of 3 when the expression of SCCA in the biological sample is higher than the reference value.

4. The method according to claim 3, wherein the reference value is a cut-off value.

5. The method according to claim 1 or 2, wherein the biological sample is non-invasively collected by tape stripping.

6. The method according to claim 1 or 2, wherein the SCCA is SCCA-1.

7. A kit for predicting the possibility that a subject, who is an infant at 2 months old, will develop atopic dermatitis by the age of 3, comprising a medium for collecting a biological sample from the face of the subject and a reagent for measuring the expression of SCCA in the biological sample collected by the medium.

8. The kit according to claim 7, wherein the medium is a tape for attaching to the skin of the subject, and the biological sample is non-invasively collected by tape stripping.

9. A system for predicting the possibility that a subject, who is an infant at 2 months old, will develop atopic dermatitis by the age of 3, the system comprising: a data acquisition unit for acquiring data related to SCCA expression from a biological sample collected from the face of the subject, who is an infant at 2 months old; a prediction unit for referring to the data acquired by the data acquisition unit and predicting that the subject, who is an infant at 2 months old, is likely to develop atopic dermatitis by the age of 3 when the SCCA expression is higher than a reference value; and a display unit for displaying the result predicted by the prediction unit.

Images