Application of MAP1S as biomarker for diagnosing autoimmune hepatitis

Abstract

The invention discloses application of MAP1S as an autoimmune hepatitis marker, belongs to the technical field of gene diagnosis and treatment of molecular biology, and aims to solve the problem that recognition of a specific marker and biochemical characteristics of autoimmune hepatitis still has certain challenging. It is found for the first time that MAP1S expression in liver tissue of an AIH patient is higher than that in normal liver tissue, and the liver cell death rate of the AIH patient in an MAP1S high-expression group is obviously higher than that in the normal liver tissue; secondly, the content of MAP1S in serum of a patient with autoimmune hepatitis is obviously higher than that of MAP1S in serum of a group of the same age, and when the serum concentration reaches 175.2 ng / ml, the Youden index reaches the highest value of 88.57%; and thirdly, the content of the MAP1S protein in the serum of the patient with the autoimmune hepatitis is positively correlated with the concentration of the inflammatory factor IL-18, which indicates that the content of the MAP1S protein in the serum is positively correlated with the severity of the autoimmune hepatitis. The results show that the content of the MAP1S in the serum of the AIH patient not only has a potential value for diagnosing the AIH, but also can be used as a target for researching the autoimmune hepatitis treatment medicine.

Description

Technical Field

[0001] The present invention belongs to the technical field of gene diagnosis and treatment in molecular biology, and in particular relates to the application of MAP1S as a biomarker for diagnosing autoimmune hepatitis. Background Art

[0002] Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease mediated by an abnormal autoimmune response, characterized by persistent liver inflammation and potentially severe damage. In clinical practice, AIH patients often present with positive serum autoantibodies, increased transaminase and immunoglobulin G (IgG) levels, and features of hepatocellular damage and necrosis in liver histology, particularly interface hepatitis as its prominent pathological feature. The specific etiology and pathogenesis of AIH are still unclear, but its annual incidence and prevalence are gradually increasing. Currently, the clinical diagnosis of AIH is mainly based on clinical manifestations, biochemical characteristics, and histological evidence. The clinical diagnosis of AIH requires a combination of serum autoantibodies such as anti-SSA / B antibodies and anti-LKM antibodies, biochemical characteristics (such as elevated serum transaminases, elevated serum total bilirubin, and elevated γ-GT), and the patient's clinical manifestations and histological findings. However, the identification of these markers and characteristics remains challenging, especially in the early stages. Many patients may not have obvious symptoms or only exhibit nonspecific symptoms, leading to failure to timely diagnosis. Approximately 34%-76% of patients have already developed into the cirrhosis stage at the time of initial diagnosis, increasing the risk of acute liver failure and mortality. Therefore, there is an urgent need to explore new diagnostic methods and strategies.

[0003] Current research focuses on exploring the pathogenesis of AIH, including genetic susceptibility, immune system dysfunction, environmental factors, viral infection, and the use of drugs that may cause immune system dysfunction. Studies have found that gender is an important risk factor for the development of AIH, with significantly more female patients than males, with a male-to-female ratio of approximately 1:4 to 1:6. AIH is more common in middle-aged women, but children and adolescents may also be affected. Globally, the peak incidence of AIH is approximately between the ages of 50 and 60, during which time women's follicle-stimulating hormone (FSH) levels experience a sharp increase, reaching their highest peak in life. This finding reveals a possible association between the peak age of AIH and the peak FSH level, suggesting that increased FSH levels may be related to the development of AIH.

[0004] FSH is a glycoprotein hormone secreted by the pituitary gland that plays a vital role in the maturation and development of ovarian follicles. In recent years, a growing number of studies have revealed that FSH and its receptors also play important roles in tissues other than the reproductive system, such as in hepatocytes, osteoclasts, and cortical neurons, and also play a key role in various diseases in postmenopausal women.

[0005] Autoimmune hepatitis (AIH) shares similarities with other autoimmune diseases, such as rheumatoid arthritis and autoimmune thyroiditis, in that they all originate from a chronic inflammatory process caused by an abnormal autoimmune response. Studies have found that elevated FSH levels are closely associated with rheumatoid arthritis and may lead to cartilage damage. Furthermore, Alzheimer's disease (AD), a common neurodegenerative disease in postmenopausal women, features aggregation of tau protein (a microtubule-associated protein (MAP) specific to nerve cells) as a prominent pathological feature, which worsens with increasing FSH levels. Treatment with FSH antibodies can improve symptoms. In 2022, a study reported that serum levels of microtubule-associated protein 1S (MAP1S) were significantly elevated in patients with autoimmune thyroiditis, exceeding 25-fold compared to healthy controls, suggesting that elevated MAP1S expression is closely associated with the onset of autoimmune thyroiditis. Taken together, these studies indicate that elevated FSH levels and MAP expression are associated with non-infectious chronic inflammatory diseases, suggesting a possible role for FSH and MAP in the development of chronic inflammatory diseases.

[0006] MAP1S is the smallest member of the microtubule-associated protein 1 (MAP1) family. Compared to other family members such as MAP1A and MAP1B, MAP1S is widely expressed in a variety of tissues beyond neurons. MAP1S not only stabilizes microtubule structure but also acts as a bridge between microtubules and mitochondria. Studies have shown that overexpression of MAP1S in hepatocytes leads to cell death. As MAP1S increases, its intracellular distribution shifts from widespread to punctate aggregates, ultimately forming a dense perinuclear aggregate network. Furthermore, MAP1S accumulation leads to a decrease in mitochondrial membrane potential, inducing pronounced perinuclear mitochondrial aggregation, ultimately causing extensive DNA degradation, nuclear disintegration, and cell death—a process known as mitochondrial aggregation and genome destruction (MAGD). Previous studies from our group have shown that the hepatitis B virus (HBV) X protein can induce upregulation of MAP1S expression in hepatocytes and is associated with hepatic inflammatory responses. These findings suggest that while MAP1S plays an important role in hepatocytes under normal physiological conditions, tight regulation of its expression is crucial for maintaining cell survival.

[0007] Liver histological examination results are an important basis for the clinical diagnosis of AIH, but it is an invasive diagnostic method. On the one hand, it may cause physical and mental damage to patients and is not easily accepted. On the other hand, the reliability of the test results may be affected by differences in physician experience, technology, and sampling quality.

[0008] Early identification and diagnosis of AIH is a major challenge. Because AIH usually progresses slowly, many patients do not have obvious clinical symptoms in the early stages of the disease, which may lead to patients delaying medical treatment or doctors neglecting the disease.

[0009] The identification of specific markers and biochemical features of AIH remains challenging. AIH patients often demonstrate positive serum autoantibodies, increased transaminase and immunoglobulin G (IgG) levels, but these findings also occur in other inflammatory liver diseases. In particular, the specificity of AIH is not strong in distinguishing liver damage from other causes. Therefore, the development of more sensitive and specific diagnostic tools is needed to improve the diagnostic accuracy of AIH. Summary of the Invention

[0010] In response to the above problems, this application provides the application of MAP1S as a biomarker for diagnosing autoimmune hepatitis. The MAP1S content in the serum of patients with autoimmune hepatitis (AIH) has potential value for diagnosing AIH, and the CUTOFF value of MAP1S in the serum of patients with autoimmune hepatitis is 175.2 ng / ml.

[0011] In a first aspect, the present invention provides use of a MAP1S protein or a substance for detecting a MAP1S protein in preparing a tool for diagnosing autoimmune hepatitis, wherein the MAP1S protein is upregulated in serum or liver tissue of autoimmune hepatitis.

[0012] In a preferred example of this aspect, the concentration of MAP1S protein in the autoimmune hepatitis serum is ≥175.2 ng / ml.

[0013] In another preferred embodiment of this aspect, the tool includes a kit and a chip.

[0014] The detection includes protein level detection, which includes immunoassay, Western blot, protein chip, chemiluminescence immunoassay, or surface plasmon resonance (SPR) method. To simplify the experimental procedure, the protein level detection also includes protein detection kits, such as ELISA detection kits, colloidal gold detection kits, immunoprecipitation kits, chemiluminescence kits, immunofluorescence kits, etc. The kits are generally equipped with corresponding instructions, which generally include items such as the company logo and name, kit name, kit composition, shelf life, application area, and usage. Users can obtain satisfactory results by following the instructions with little or no optimization.

[0015] Preferably, the immunoassay method is ELISA detection and / or colloidal gold detection.

[0016] The ELISA method uses an ELISA detection kit, which includes: a solid phase carrier coated with MAP1S monoclonal antibody, an enzyme-labeled antibody, an enzyme substrate, a protein standard, a negative control, a diluent, a washing solution, an enzyme reaction stop solution, etc.

[0017] In a second aspect, the present invention provides the use of MAP1S protein or a substance for detecting MAP1S protein in the preparation of a product for evaluating the therapeutic effect of autoimmune hepatitis or judging the prognosis of autoimmune hepatitis, wherein the expression of the MAP1S protein is downregulated in the serum or liver tissue of autoimmune hepatitis after treatment.

[0018] In a third aspect, the present invention provides the use of MAP1S protein or a substance for detecting MAP1S protein for screening drugs for preventing, diagnosing, evaluating the prognosis or treating autoimmune hepatitis.

[0019] In the context of the present invention, microtubule-associated protein 1S (MAP1S) refers to Homosapiens (Human) MAP1S, UniprotKB accession number Q66K74.

[0020] Compared with the prior art, the present invention has the following advantages:

[0021] This study, published in the journal Nature Medicine, demonstrates for the first time that serum MAP1S levels in patients with autoimmune hepatitis are significantly higher than those in the same age group. Furthermore, the Youden index reaches a maximum value of 88.57% at a serum concentration of 175.2 ng / ml. This results in a cutoff value of 175.2 ng / ml for diagnosing AIH, with an accuracy of 88.57%. This study demonstrates that serum MAP1S levels in patients with autoimmune hepatitis (AIH) have potential diagnostic value. MAP1S may also serve as a target for drug development in the treatment of autoimmune hepatitis. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 (A) MAP1S is highly expressed in hepatocytes of AIH patients, and (B) a statistical analysis chart is shown.

[0023] Figure 2 The results showed that the expression level of IL-18 in liver tissue of AIH patients was significantly increased.

[0024] Figure 3 It was shown that the cytochrome C content in the liver tissue of AIH patients with high MAP1S expression was significantly reduced.

[0025] Figure 4 It showed that the number of apoptotic cells in the liver tissue of AIH patients with high MAP1S expression was significantly higher than that in the MAP1S low expression group and HD. Figure 4A. Immunofluorescence analysis of apoptotic cells in normal and AIH liver tissues. B. Statistical analysis of the differences in the proportion of apoptotic hepatocytes between normal and AIH liver tissues. C. Statistical analysis of the proportion of apoptotic non-hepatocytes among total apoptotic cells in normal and AIH liver tissues. D. Statistical analysis of the differences in the proportion of apoptotic hepatocytes among the HD, MAP1S-L, and MAP1S-H groups. E. Statistical analysis of the proportion of apoptotic non-hepatocytes among total apoptotic cells among the HD, MAP1S-L, and MAP1S-H groups.

[0026] Figure 5 The results showed that the levels of MAP1S (A), IL18 (C) and FSH (E) in the serum of AIH patients were significantly higher than those in healthy women of the same age group. Figure 5 B, D, and F show the correlation analysis results between FSH and MAP1S, FSH and IL18, and MAP1S and IL18, respectively.

[0027] Figure 6 .ROC curve of MAP1S.

[0028] Figure 7 FSH stimulates MAP1S protein expression in the hepatocellular carcinoma cell line HepaRG. A. Western blot analysis shows elevated MAP1S expression in HepaRG cells after treatment with different FSH concentrations (0, 5, 10, 25, 50, and 100 ng / ml). B. Statistical analysis of protein expression by Western blot (*p < 0.05, **p < 0.01, ***p < 0.005, ****p < 0.001). DETAILED DESCRIPTION

[0029] The preferred embodiments of the present invention are described in detail below with reference to the accompanying drawings so that the advantages and features of the present invention can be more easily understood by those skilled in the art, thereby making a clearer and more precise definition of the protection scope of the present invention.

[0030] Example 1: Immunohistochemical detection of MAP1S expression in liver tissue

[0031] Paraffin sections of liver tissue adjacent to hepatic hemangioma (HCH) in menopausal women (column 1) and from AIH (column 2) were labeled with MAP1S antibodies (Biorbyt, #orb251641, UK) and analyzed for MAP1S expression by immunohistochemistry. Brown indicates positive MAP1S antibody labeling, while blue indicates hematoxylin-labeled nuclei. Results were observed under a microscope at 20x (first row) and 40x (second row), respectively. B. MAP1S expression in AIH hepatocytes was significantly stronger than in HCH (n = 4).

[0032] By immunohistochemical analysis, we found that the expression intensity and positive staining area of MAP1S in the liver cells of AIH patients were significantly higher than those in the normal liver tissue (HCH) adjacent to the hemangioma of female patients with hepatic hemangioma of the same age group, with statistical significance (P < 0.05) (see Figure 1 A, B). The results are shown in Figure 1 Small Figure 1 A, 1B; among them, small Figure 1 A is a representative image of liver samples detected by immunohistochemistry for MAP1S expression. Figure 1 B shows the statistical analysis results based on expression intensity scores. The expression intensity score is calculated as the product of staining intensity and positivity rate. Staining intensity is classified as follows: 0: no specific staining of cells; 1+: weak staining of cells; 2+: moderately positive staining; 3+: strong and uniform staining of cells. The positivity rate is classified as follows: 0: 0% of liver cancer cells are stained; 1: 1-25% of liver cells are stained; 2: 25-50% of liver cells are stained; 3: 51-75% of liver cells are stained; 4: 76-100% of liver cells are stained. The final expression intensity score was used to evaluate the expression intensity of MAP1S: 0-4 points indicated low expression intensity, 5-8 indicated medium expression intensity, and 12 points indicated high expression intensity (refer to Allison KH et al., Estrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology / College of American Pathologists Guideline Update. Arch Pathol Lab Med. 2020 May; 144(5): 545-563. doi: 10.5858 / arpa.2019-0904-SA. Epub 2020 Jan 13. PMID: 31928354).

[0033] Conclusion: The expression of MAP1S in AIH hepatocytes was significantly higher than that in HCH.

[0034] Example 2: Detection of inflammatory factor IL-18 expression by protein profiling of liver tissue

[0035] We used the isobaric tag-based relative and absolute quantification (iTRAQ) method to perform proteomic analysis of liver tissue. First, normal liver tissue samples (n = 6) and autoimmune hepatitis liver tissue samples (n = 19) were collected and protein extracted. Proteins were reduced, alkylated, and then digested with trypsin. The peptide mixtures obtained from each sample group were labeled with different iTRAQ reagents. Subsequently, equal amounts of labeled peptides from each sample were pooled. MS / MS detection and analysis were performed using QLbio (Qinglian Biotech Co., Ltd., Beijing, China). Proteins with a multiplication factor greater than or less than 1.2 and a P value ≤ 0.05 were considered differentially expressed proteins (DEPs) (completed by Qinglian Biotech Co., Ltd.). Through protein spectrum analysis, we found that the abundance of IL-18 in the liver tissue of AIH patients (N = 19) was 0.6098, which was significantly higher than the abundance of 0.2534 in normal liver tissue (n = 6), and the expression level was significantly increased (log2FC>1.2, P = 0.0165), indicating that inflammasomes were activated in the liver tissue of patients with autoimmune liver disease and the level of inflammatory cytokine IL-18 was significantly increased. Figure 2 .

[0036] Conclusion: Inflammasome activation and IL-18 levels in liver tissue of patients with autoimmune liver disease are significantly increased.

[0037] Example 3: Liver tissue protein profiling to detect the correlation between MAP1S expression and inflammatory factors IL18 and cytochrome C levels

[0038] Given that immunohistochemistry detected high expression of MAP1S in hepatocytes, we further analyzed the expression of MAP1S in liver tissues of AIH patients and healthy volunteers (HD) based on the results of protein spectrum analysis. In the livers of the healthy control group, the average abundance of MAP1S protein was 0.5715 (n=6). Based on this standard, AIH was divided into two groups: one group with a mean of 0.6659±0.02695, higher than 0.5715, was named MAP1S-H group (n=7), and the other group with a mean of 0.5059±0.02313, lower than 0.5715, was named MAP1S-L group (n=12); among them, the MAP1S-H group accounted for 36.84% (7 / 19) and the MAP1S-L group accounted for 63.16%. The cytochrome C (CYC) content in the mitochondria of the two groups was analyzed. The results showed that the CYC content in the liver tissue of the MAP1S-H group was 2.132±0.2716, which was significantly lower than that of the MAP1S-L group (3.429±0.3721) (P=0.0065) and the HD group (3.404 (P=0.0392). There was no significant difference in CYC content between the MAP1S-L and HD groups (P>0.05) (see Figure 3 ); the CYC content in the liver tissue of the MAP1S-H group was only 62.18% of that in the MAP1S-L group, indicating that high expression of MAP1S in the liver tissue of AIH patients led to mitochondrial damage and leakage of its contents, such as CYC.

[0039] The IL18 levels in the MAP1S high expression group and low expression group were 0.7206±0.1742 and 0.4199±0.3007, respectively, which were higher than the healthy control group (0.2534), but there was no significant difference (P=0.0688). However, the IL18 level in the MAP1S-H group was lower than that in the MAP1S-L group (P=0.0909) (see Figure 3 Given that IL-18 is an effector product produced by the activation of intracellular inflammasomes, and that patients in the MAP1S high expression group had mitochondrial damage, the release of mitochondrial contents led to liver cell death, which in turn led to the release of inflammatory factors into the bloodstream and a relative decrease in IL-18 levels in liver tissue, this may be the reason why the IL-18 content in the MAP1S high expression group was lower than that in the MAP1S low expression group in liver tissue protein profiling.

[0040] The above research results show that: 1. The expression level of MAP1S in the liver tissue of some AIH patients was significantly higher than that in the healthy control group; 2. The mitochondrial damage of AIH patients in the MAP1S high expression group was significantly reduced, and the cytochrome C protein content was significantly reduced. The high expression of MAP1S in liver cells may cause mitochondrial damage.

[0041] Conclusion: Overexpression of MAP1S in hepatocytes may cause mitochondrial damage and inflammasome activation.

[0042] Example 4: Immunofluorescence detection of apoptotic cells in liver tissue

[0043] The inventors used the TUNEL method (Servicebio, G1504, Wuhan, China) to detect apoptotic cells in liver tissues of AIH patients (n=19) and healthy volunteers (HD) (n=6). The cell nuclei stained with DAPI (Servicebio, G1012, Wuhan, China) appear blue under ultraviolet excitation. The TUNEL kit is labeled with CY3 fluorescein and emits red fluorescence under laser excitation at a wavelength of 510-560 nm, indicating that the nuclei of positive apoptotic cells appear red. The CK18 antibody (Servicebio, GB114832, Wuhan, China, 1:300) was used to label hepatocytes. The FITC fluorescent-labeled secondary antibody (Servicebio, GB21303, Wuhan, China, 1:300) emits green fluorescence under laser excitation at a wavelength of 465-495 nm, indicating that the cytoplasm of CK18-positive hepatocytes appears green. Figure 4 A shows immunofluorescence detection of apoptotic cells (red), hepatocytes (green), and nuclei (blue) in normal liver tissue (HD, first row), AIH liver tissue with low MAP1S expression (MAP1S-L, second row), and AIH liver tissue with high MAP1S expression (MAP1S-H, third row). Figure 4 B. Statistical analysis: The proportion of apoptotic hepatocytes in total cells (AHIAC) = the number of apoptotic hepatocytes / total number of cell nuclei*100%; the proportion of apoptotic hepatocytes in total apoptotic cells (AHIAAC) = the number of apoptotic hepatocytes / total number of apoptotic cells*100%; the proportion of apoptotic hepatocytes in total hepatocytes (AHIAH) = the number of apoptotic hepatocytes / total number of hepatocytes*100%. Figure 4 C Statistical analysis: the ratio of apoptotic non-hepatocytes to total apoptotic cells = 1-AHIAAC, and the ratio of apoptotic hepatocytes to total apoptotic cells (AHIAAC). Figure 4 D, E Statistical analysis of AHIAC, AHIAAC, and AHIAH in the HD, MAP1S-L, and MAP1S-H groups. The results showed that the hepatocyte apoptosis rate in the liver tissues of AIH patients with high MAP1S expression was significantly higher than that in the liver tissues of healthy volunteers and AIH with low MAP1S expression, suggesting that high MAP1S expression may be associated with hepatocyte death.

[0044] Conclusion: Overexpression of MAP1S may be associated with hepatocyte death.

[0045] Example 5: ELISA detection of MAP1S, FSH and IL18 levels in serum

[0046] The inventors used ELISA to detect peripheral serum of 35 AIH patients and 30 age-matched healthy volunteers (HD). Figure 5 The results in A, C, and E showed that the levels of MAP1S (N=35) (Jingmei Biotechnology Co., Ltd., JM-7167H1), FSH (N=35) (Jingmei Biotechnology Co., Ltd., JM-7167H2), and IL18 (N=35) (Jingmei Biotechnology Co., Ltd., JM-7167H3) in AIH patients were significantly higher than those in the HD group (all P values were less than 0.0001); Figure 5 The results of correlation analysis in B, D, and F showed that FSH was positively correlated with MAP1S and IL18, and MAP1S was positively correlated with IL18 (Pearson r was 0.7704, 0.8977, and 0.7454, respectively, and P values were all less than 0.0001).

[0047] further, Figure 6 ROC curve analysis showed that the area under the ROC curve (AUC) for MAP1S was as high as 0.9838, with a statistically significant difference (P<0.0001). Furthermore, when its serum concentration reached 175.2 ng / ml, its Youden index reached a maximum value of 88.57% (as shown in Table 1 below). Thus, its cutoff value for diagnosing AIH was 175.2 ng / ml, with an accuracy of 88.57%. These findings suggest that serum MAP1S levels have potential value in diagnosing AIH and that MAP1S may serve as a target for drug development in the treatment of autoimmune hepatitis.

[0048] Table 1 Analysis of Youden index of MAP1S

[0049] MAP1S (ng / ml) Sensitivity% 95％Cl Specificity% 95％Cl2 Likelihood ratio Youden's Inde ′165.9 94.29 81.39% to 98.98% 86.67 70.32% to 94.69% .071 0.8096 >168.9 91.43 77.62% to 97.04% 86.67 70.32% to 94.69% 6.857 0.781 >170.2 91.43 77.62% to 97.04% 90 74.38% to 96.54% 9.143 0.8143 >170.7 91.43 77.62% to 97.04% 93.33 78.68% to 98.82% 13.71 0.8476 >172.8 91.43 77.62% to 97.04% 96.67 83.33% to 99.83% 27.43 0.881 >175.0 88.57 74.05% to 95.46% 96.67 83.33% to 99.83% 26.57 0.8524 >175.2 88.57 74.05% to 95.46% 100 88.65% to 100.0% 0.8857 >176.9 85.71 70.62% to 93.74% 100 88.65% to 100.0% 0.8571 >179.6 82.86 67.32% to 91.90% 100 88.65% to 100.0% 0.8286 >183.5 80 64.11% to 89.96% 100 88.65% to 100.0% .8

[0050] Conclusion: The serum MAP1S level in patients has potential value in diagnosing AIH.

[0051] Example 6: FSH stimulates MAP1S protein expression in the liver cancer cell line HepaRG

[0052] Considering that AIH mainly occurs in menopausal women aged 50-60 years, and FSH levels in women of this age group reach their peak, we treated HepaRG cells with different concentrations of FSH (HY-P74133, MCE, USA) (0, 10ng / ml, 25ng / ml, 50ng / ml, 100ng / ml, 150ng / ml) for 12 hours, and then detected by immunoblotting. The results showed that FSH could significantly enhance the expression of MAP1S protein in a dose-dependent manner (see Figure 7A, B). A. Western Blot showed that MAP1S expression increased in HepaRG cells after treatment with different concentrations of FSH (0, 5, 10, 25, 50, 100 ng / ml). B. Statistical analysis of protein expression by Western Blot (*p<0.05, **, p<0.01, ***, p<0.005, ****, p<0.001)

[0053] Conclusion: FSH promotes the expression of MAP1S protein in the hepatocellular carcinoma cell line HepaRG.

[0054] The above descriptions are merely a few embodiments of the present application and do not constitute any form of limitation to the present application. Although the present application discloses the preferred embodiments as above, they are not intended to limit the present application. Any technical personnel familiar with the present profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. Use of a MAP1S protein or a substance for detecting a MAP1S protein in the preparation of a tool for diagnosing autoimmune hepatitis, wherein the MAP1S protein is upregulated in serum or liver tissue of patients with autoimmune hepatitis.

2. The use according to claim 1, characterized in that The concentration of MAP1S protein in the autoimmune hepatitis serum or liver tissue is ≥175.2 ng / ml.

3. The use according to claim 1, characterized in that The tools include a test kit and a chip.

4. Use of a MAP1S protein or a substance for detecting a MAP1S protein in the preparation of a product for evaluating the therapeutic effect of autoimmune hepatitis or determining the prognosis of autoimmune hepatitis, wherein the expression of the MAP1S protein is downregulated in the serum or liver tissue of autoimmune hepatitis after treatment.

5. The use according to claim 4, characterized in that The tools include a test kit and a chip.

6. A kit for diagnosing autoimmune hepatitis, characterized in that: The kit includes a biomarker detection reagent, which contains chemical magnetic beads and a chemiluminescent substrate. The biomarker is MAP1S, and the biomarker is used to detect tissue or serum samples.

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