Use of trimer 69 in preparation of a kit for aiding diagnosis of systemic lupus erythematosus

Abstract

The application relates to the field of biological medicine, and provides application of TRIM69 in preparation of a kit for auxiliary diagnosis of systemic lupus erythematosus. The kit is used for auxiliary diagnosis of systemic lupus erythematosus by detecting the TRIM69 level. The mRNA expression amount, the protein expression amount and / or the concentration of TRIM69 are used for auxiliary diagnosis of systemic lupus erythematosus. TRIM69 serves as a biomarker, and has important values in aspects of auxiliary diagnosis, disease activity monitoring, prognosis evaluation and improvement of diagnosis efficiency. Not only can the doctor identify high-risk patients earlier, but also can provide a basis for individualized treatment, so that the long-term prognosis of the systemic lupus erythematosus patient is improved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological medicine, and particularly relates to application of TRIM69 in preparation of a kit for auxiliary diagnosis of systemic lupus erythematosus. BACKGROUND

[0002] Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple systems and organs. Its pathogenesis is complex, and its clinical manifestations are highly heterogeneous. Early symptoms are easily confused with other diseases such as rheumatoid arthritis and Sjogren's syndrome. Therefore, accurate diagnosis of systemic lupus erythematosus is crucial for controlling disease progression, reducing the risk of organ damage, and improving patient outcomes.

[0003] Currently, the diagnosis of systemic lupus erythematosus mainly relies on the comprehensive judgment of clinical symptoms, laboratory tests, and imaging evaluations, but it lacks specificity and takes a long time, and patients may experience irreversible organ damage. The commonly used immunological indicators for systemic lupus erythematosus have many limitations, such as high false positive rate of ANA, low sensitivity of anti-dsDNA antibody and anti-Sm antibody, leading to missed diagnosis in some cases. SUMMARY

[0004] In view of the deficiencies of the prior art, the application provides application of TRIM69 in preparation of a kit for auxiliary diagnosis of systemic lupus erythematosus, which aims to solve the problems mentioned in the background.

[0005] In the first aspect, the application provides application of TRIM69 in preparation of a kit for auxiliary diagnosis of systemic lupus erythematosus, which assists in diagnosing systemic lupus erythematosus by detecting the level of TRIM69.

[0006] Further, the kit assists in diagnosing systemic lupus erythematosus by detecting the mRNA expression, protein expression and / or concentration of TRIM69.

[0007] Further, the kit includes an antibody for detecting TRIM69 protein or a PCR primer for detecting a cDNA chain of TRIM69 gene.

[0008] Further, the biological sample detected by the kit includes peripheral blood or serum.

[0009] Further, the mRNA expression of TRIM69 in the peripheral blood of a systemic lupus erythematosus patient is increased.

[0010] The expression and / or concentration of TRIM69 protein in the serum of a systemic lupus erythematosus patient is increased.

[0011] Further, the kit assists in diagnosing the subject as a systemic lupus erythematosus patient when the concentration of TRIM69 protein in the serum of the subject is greater than 187.2 pg / ml, wherein the subject does not include a rheumatoid arthritis patient.

[0012] In a second aspect, the present application provides a prediction model for diagnosing systemic lupus erythematosus based on the level of TRIM69 in serum, hemoglobin, and the neutrophil-to-lymphocyte ratio, and the prediction model is expressed by the formula:

[0013] ;

[0014] In the formula, Q is the prediction value, HGB is hemoglobin, NLR is the neutrophil-to-lymphocyte ratio, and TRIM69 is the expression level of the protein.

[0015] Further, when the prediction value is greater than 0.324, the subject is diagnosed as a systemic lupus erythematosus patient, wherein the subject does not include a rheumatoid arthritis patient.

[0016] Further, when the prediction value is greater than 1.558, the subject is assisted in being diagnosed as a systemic lupus erythematosus patient.

[0017] The present application has the following beneficial effects:

[0018] (1) TRIM69 is applied to the preparation of a kit for assisting in the diagnosis of systemic lupus erythematosus. By the mRNA expression level, the expression level and / or the concentration of TRIM69, the diagnosis of systemic lupus erythematosus is assisted. TRIM69 serves as a biomarker and has important value in assisting in diagnosis, monitoring disease activity, evaluating prognosis, and improving diagnostic efficiency. Not only can it help doctors identify high-risk patients earlier, but it can also provide a basis for individualized treatment, thereby improving the long-term prognosis of systemic lupus erythematosus patients. With more research, TRIM69 is expected to become a key tool in the management of systemic lupus erythematosus.

[0019] (2) The prediction model constructed based on the level of TRIM69 in serum, hemoglobin, and the neutrophil-to-lymphocyte ratio for diagnosing systemic lupus erythematosus can more accurately identify true systemic lupus erythematosus patients (high sensitivity) and effectively exclude non-patients (high specificity), reducing the risk of misdiagnosis and missed diagnosis, and providing more reliable diagnostic evidence for clinicians. Compared with a single indicator, a multi-element prediction model has stronger comprehensive diagnostic ability and can integrate information provided by different indicators to overcome the limitations of a single indicator (such as large volatility and insufficient specificity), thereby improving the stability and accuracy of overall prediction. BRIEF DESCRIPTION OF DRAWINGS

[0020] The exemplary embodiments of this application can be more fully understood by reference to the following drawings:

[0021] Figure 1 is the RT-qPCR detection result and ELISA detection result of Example 2 of the present application, wherein:

[0022] Figure 1 A in is a statistical chart of RT-qPCR detection results of TRIM69 expression in peripheral blood of the systemic lupus erythematosus patient group, the rheumatoid arthritis patient group and the healthy control group, GADPH is used as an internal reference, *** indicates p<0.001, and **** indicates p<0.0001;

[0023] Figure 1 B in is a statistical chart of RT-qPCR detection results of TRIM69 expression in peripheral blood of the systemic lupus erythematosus patient group, the rheumatoid arthritis patient + healthy control group, **** indicates p<0.0001;

[0024] Figure 1 C in is a statistical chart of TRIM69 protein concentration in serum of the systemic lupus erythematosus patient group, the rheumatoid arthritis patient group and the healthy control group, ** indicates p<0.01, and **** indicates p<0.0001;

[0025] Figure 1 D in is a statistical chart of TRIM69 protein concentration in serum of the systemic lupus erythematosus patient group, the rheumatoid arthritis patient + healthy control group, *** indicates p<0.001.

[0026] Figure 2 is a correlation analysis result chart of TRIM69 level in serum of the systemic lupus erythematosus patient and clinical characteristics of the systemic lupus erythematosus patient in Example 3 of the present application, wherein:

[0027] Figure 2 A in is a correlation analysis result chart of TRIM69 protein concentration in serum and white blood cell count, p<0.0001;

[0028] Figure 2 B in is a correlation analysis result chart of TRIM69 protein concentration in serum and absolute value of lymphocytes, p<0.0001;

[0029] Figure 2 C in is a correlation analysis result chart of TRIM69 protein concentration in serum and absolute value of monocytes, p<0.0001;

[0030] Figure 2D in FIG. 1 is a graph of correlation analysis results of TRIM69 protein concentration in serum and absolute value of neutrophil, p<0.0001;

[0031] Figure 2 E in FIG. 1 is a graph of correlation analysis results of TRIM69 protein concentration in serum and platelet to lymphocyte ratio, p<0.0001;

[0032] Figure 2 F in FIG. 1 is a graph of correlation analysis results of TRIM69 protein concentration in serum and complement C3, p<0.0001;

[0033] Figure 2 G in FIG. 1 is a statistical graph of TRIM69 protein concentration in serum of systemic lupus erythematosus patients with positive anti-SSA and negative anti-SSA, p=0.0181;

[0034] Figure 2 H in FIG. 1 is a statistical graph of TRIM69 protein concentration in serum of systemic lupus erythematosus patients with positive anti-Ro52 and negative anti-Ro52, p=0.0165;

[0035] Figure 2 I in FIG. 1 is a statistical graph of TRIM69 protein concentration in serum of systemic lupus erythematosus patients with positive anti-Sm and negative anti-Sm, p=0.0149.

[0036] Figure 3 FIG. 1 is a ROC curve analysis result graph of Example 4 of the present application, wherein:

[0037] Figure 3 A in FIG. 1 is a ROC curve analysis result graph of TRIM69 level in serum of systemic lupus erythematosus patients and healthy controls, P<0.0001;

[0038] Figure 3 B in FIG. 1 is a ROC curve analysis result graph of TRIM69 level in serum of systemic lupus erythematosus patients and rheumatoid arthritis patients + healthy controls, P<0.0001.

[0039] Figure 4 FIG. 1 is a ROC curve analysis result graph of Example 4 of the present application, wherein:

[0040] Figure 4 A in FIG. 1 is a ROC curve analysis result graph of TRIM69 level in serum of systemic lupus erythematosus patients and healthy controls, P<0.0001;

[0041] Figure 4 B in FIG. 1 is a ROC curve analysis result graph of TRIM69 level in serum of systemic lupus erythematosus patients and rheumatoid arthritis patients + healthy controls, P<0.0001.

[0042] Figure 4 C in the figure is a statistical graph of the predicted values ​​of the systemic lupus erythematosus patient group and the rheumatoid arthritis patient + healthy control group, p < 0.0001;

[0043] Figure 4 D in the figure is the ROC analysis of the prediction model, which distinguishes patients with systemic lupus erythematosus from patients with rheumatoid arthritis and healthy controls, P < 0.0001.

[0044] Figure 5 is the analysis result of the prediction model of serum TRIM69 level, red blood cell count, and lymphocyte-to-monocyte ratio in Example 5 of the present invention, wherein:

[0045] Figure 5 A in the figure is a statistical diagram of the predicted values ​​of the systemic lupus erythematosus patient group and the healthy control group, p=0.0359;

[0046] Figure 5 Figure B is a statistical graph of the predicted values ​​of the systemic lupus erythematosus patient group and the rheumatoid arthritis patient + healthy control group, p=0.9196;

[0047] Figure 5 C in the figure is the ROC analysis of the prediction model, which distinguishes patients with systemic lupus erythematosus from healthy controls with P=0.036.

[0048] Figure 6 : This is a graph showing the analysis results of the relationship between the prediction model constructed using serum TRIM69 levels, hemoglobin, and neutrophil-to-lymphocyte ratio in Example 6 of the present invention and the clinical characteristics of patients with systemic lupus erythematosus, wherein:

[0049] Figure 6 A in the figure is the correlation analysis result between the prediction model and the percentage of neutrophils, p=0.0001;

[0050] Figure 6 Figure B is the correlation analysis result between the prediction model and the platelet-to-lymphocyte ratio, p < 0.0001;

[0051] Figure 6 C in the figure is the correlation analysis result between the prediction model and the neutrophil-to-lymphocyte ratio, p < 0.0001;

[0052] Figure 6 D in the figure is the correlation analysis result between the prediction model and red blood cell count, p=0.0003;

[0053] Figure 6 E in the figure is the correlation analysis result between the prediction model and hemoglobin percentage, p < 0.0001;

[0054] Figure 6 F in FIG. 1 is a correlation analysis result graph of the prediction model and hematocrit, p<0.0001;

[0055] Figure 6 G in FIG. 1 is a correlation analysis result graph of the prediction model and absolute value of lymphocytes, p<0.0001;

[0056] Figure 1 H in FIG. 1 is a correlation analysis result graph of the prediction model and percentage of lymphocytes, p<0.0001;

[0057] Figure 1 I in FIG. 1 is a correlation analysis result graph of the prediction model and ratio of lymphocytes to monocytes, p=0.0044. DETAILED DESCRIPTION

[0058] In order to make the technical problems to be solved by the present application, technical solutions and beneficial effects more clearly understood, the present application will be further described in detail below in combination with the drawings and examples. It should be understood that the specific examples described herein are only used to explain the present application, and are not intended to limit the present application.

[0059] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs; the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application.

[0060] The embodiments of the present application provide application of TRIM69 in preparation of a kit for assisting diagnosis of systemic lupus erythematosus, and the kit assists diagnosis of systemic lupus erythematosus by detecting the level of TRIM69.

[0061] In some embodiments, the kit assists diagnosis of systemic lupus erythematosus by detecting the mRNA expression amount, protein expression amount and / or concentration of TRIM69.

[0062] In some embodiments, the kit comprises an antibody for detecting TRIM69 protein or a PCR primer of a cDNA chain of TRIM69 gene.

[0063] In some embodiments, the biological sample detected by the kit comprises peripheral blood or serum.

[0064] In some embodiments, the mRNA expression amount of TRIM69 in peripheral blood of a systemic lupus erythematosus patient is increased;

[0065] The protein expression amount and / or concentration of TRIM69 in serum of a systemic lupus erythematosus patient is increased.

[0066] In some embodiments, the kit assists in diagnosing the subject as a systemic lupus erythematosus patient when the concentration of TRIM69 protein in the serum of the subject is >187.2 pg / ml by ELISA method, wherein the subject does not include a rheumatoid arthritis patient.

[0067] In some embodiments, the present application provides a prediction model for diagnosing systemic lupus erythematosus based on the levels of TRIM69 in serum, hemoglobin, and neutrophil-to-lymphocyte ratio, which is expressed as:

[0068] ;

[0069] In the formula: Q is the prediction value, HGB is hemoglobin, NLR is neutrophil-to-lymphocyte ratio, and TRIM69 is the expression level of the protein.

[0070] In some embodiments, the higher the prediction value, the higher the risk of systemic lupus erythematosus.

[0071] In some embodiments, the prediction value > 0.324, the subject is diagnosed as a systemic lupus erythematosus patient, wherein the subject does not include a rheumatoid arthritis patient.

[0072] In some embodiments, the prediction value > 1.558, the subject is diagnosed as a systemic lupus erythematosus patient.

[0073] Sample collection and analysis:

[0074] (1) Experimental subjects: From June 2024 to March 2025, systemic lupus erythematosus patients who met the American College of Rheumatology (ACR) revised systemic lupus erythematosus diagnostic criteria were recruited in the First Affiliated Hospital of Nanchang University, and age- and sex-matched healthy controls (without autoimmune diseases or other inflammatory diseases) were selected. The disease activity of systemic lupus erythematosus patients was evaluated using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and they were divided into stable phase (SLEDAI 0-9 points) and active phase (SLEDAI ≥ 10 points) according to the score. Among the systemic lupus erythematosus patients, 9 newly diagnosed patients had not received immunosuppressive drugs or corticosteroid treatment before enrollment, and the remaining patients had been diagnosed, treated, and relapsed. At the same time, rheumatoid arthritis (RA) patients admitted to the hospital were included as disease controls, and all rheumatoid arthritis patients met the revised American College of Rheumatology criteria for rheumatoid arthritis. This program has been approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University, approval number: (2023) CDYFYYLK(01-002), and all participants have signed a written informed consent form.

[0075] (2) RNA extraction: EDTA-anticoagulated serum was drawn from the experimental subjects for collection of peripheral blood; TRIzol® (Thermo Fisher Scientific) was used to extract RNA from whole blood, following the manufacturer's protocol. The concentration of RNA was quantified and identified by NanoDrop ND-1000 spectrophotometer (Agilent Technologies), and stored at -80°C.

[0076] (3) RT-qPCR (reverse transcription-quantitative polymerase chain reaction) analysis: total RNA was reverse transcribed into cDNA using a reverse transcription kit (Talab). The cDNA sample was amplified by qPCR on an ABI 7500 real-time PCR instrument (Applied Biosystems; Thermo Fisher Scientific). The primers for TRIM69 were: forward primer: 5'-CTTGCCATCCAACAGGGTCAA-3' (SEQ ID NO. 1), reverse primer: 5'-TTCCTTGTGAGCAGCAATAGC-3' (SEQ ID NO. 2), designed by Primers 5 software and verified by primer BLAST, and synthesized by Shanghai Sheng Gong. In each sample, GADPH was used as an internal reference, forward primer: 5'-TGCACCACCAACTGCTTAGC-3' (SEQ ID NO. 3), reverse primer: 5'-GGCATGGACTGTGGTCATGAG-3' (SEQ ID NO. 4). All RT-qPCR data were analyzed using the 2- AACt method.

[0077] (4) ELISA method (enzyme-linked immunosorbent assay): whole blood samples were collected and centrifuged (3500 rpm for 10 minutes) to obtain serum, which was stored at -80°C. The concentration of TRIM69 protein in the serum was determined by an ELISA kit (Abexis, abx383943).

[0078] (5) Blood routine, serum inflammatory markers and autoantibody detection: The blood routine and urine routine items were detected by using Thermo X2100 (Japan Hanshin Thermo Fisher Corporation) and Thermo UF1000i (Japan Thermo Fisher Corporation) equipment. The C3 (complement 3), C4 (complement 4), CRP (C-reactive protein) and IgG (immunoglobulin G) levels in serum were determined by the immune 800 system (Beckman Coulter) using the turbidimetric method. The ESR (erythrocyte sedimentation rate) was determined according to the manufacturer's instructions. The IgG anti-dsDNA in serum was detected using an ELISA kit (Shanghai Keyin Company), and ANA (anti-nuclear antibody) was determined using an indirect immunofluorescence method (OriGene). Anti-ENA (anti-extractable nuclear antigen antibody) was determined using a linear immunoassay kit (OriGene, Lubeck, Germany), and anti-ENA included anti-SSA (anti-sjogren's syndrome A antigen antibody), anti-SSB (anti-sjogren's syndrome B antigen antibody), anti-Ro52 (anti-trimeric protein 21 antibody), anti-Sm (anti-Smith antibody), anti-PO (anti-phospholipase kinase antibody), anti-U1-snRNP (anti-U1 small nuclear ribonucleoprotein antibody), anti-ANuA (anti-anti-nuclear antibody), and anti-Histone (anti-histone antibody).

[0079] (6) Statistical analysis: All data were presented in the form of mean ± standard error of the mean (SEM). Statistical analysis was performed using Graphpad prism 10.1.2 software. For comparison between two groups, Student's t-test or Mann-Whitney U-test was used according to whether the data were normally distributed. For comparison among three groups, the Kruskal-Wallis test was used, followed by the Dunn's post-test. Correlation analysis was performed using the Pearson or Spearman method. The predictive performance of TRIM69, blood routine parameters and prediction models was evaluated using the receiver operating characteristic (ROC) curve.

[0080] Example 1:

[0081] Detailed demographic characteristics of 199 participants (72 systemic lupus erythematosus patients, 62 healthy controls and 65 rheumatoid arthritis patients) were statistically analyzed.

[0082] The statistical results are shown in Table 1. Compared with healthy controls, patients with systemic lupus erythematosus exhibited significantly increased platelet distribution width (PDW), monocyte count and percentage (M, M%), and neutrophil count and percentage (N, N%), while red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT), mean platelet volume (MPV), and lymphocyte count and percentage (L, L%) were significantly decreased. Compared with patients with rheumatoid arthritis, patients with systemic lupus erythematosus had significantly increased monocyte count and percentage (M, M%), while hemoglobin (HGB), hematocrit (HCT), platelet count (PLT), and platelet volume (PCT) were significantly decreased.

[0083] Table 1 Clinical characteristics of patients with systemic lupus erythematosus, healthy subjects, and rheumatoid arthritis

[0084]

[0085] In the table, * indicates systemic lupus erythematosus versus healthy control group, p < 0.05; # indicates systemic lupus erythematosus versus rheumatoid arthritis group, p < 0.05; age, systemic lupus erythematosus disease activity score, erythrocyte sedimentation rate, hemoglobin, and platelet data have been rounded to two decimal places.

[0086] Example 2:

[0087] (1) The mRNA levels of TRIM69 in the peripheral blood of patients with systemic lupus erythematosus, rheumatoid arthritis and healthy controls were compared by RT-qPCR.

[0088] RT-qPCR test results are as follows Figure 1 As shown in A and B, the results showed that the mRNA expression of TRIM69 in the peripheral blood of the systemic lupus erythematosus patient group was significantly upregulated, not only significantly higher than that of the healthy control group, but also significantly higher than that of the rheumatoid arthritis patient group ( Figure 2 In addition, the mRNA level of TRIM69 in the peripheral blood of the SLE group was significantly higher than that of the SLE group plus the healthy control group (Figure 1, A).

[0089] (2) Since the significant differences in mRNA levels were mainly observed in patients with systemic lupus erythematosus, the TRIM69 level (protein) in the serum of patients with systemic lupus erythematosus was detected by ELISA (enzyme-linked immunosorbent assay).

[0090] ELISA test results Figure 2TRIM69 levels in the serum of the systemic lupus erythematosus patient group were significantly higher than those in the rheumatoid arthritis patient + healthy control group (Fig. 1D).

[0091] Example 3:

[0092] The correlation between the TRIM69 levels (protein) in the serum of the systemic lupus erythematosus patients and the clinical characteristics of the systemic lupus erythematosus patients was analyzed.

[0093] The results of the correlation analysis between the TRIM69 levels in the serum of the systemic lupus erythematosus patients and the clinical characteristics of the systemic lupus erythematosus patients are shown in Figure 3 The results showed that the TRIM69 levels in the serum were negatively correlated with the counts of various immune cells, including total white blood cells (r = -0.5729, Fig. 2A), lymphocytes (r = -0.4866, Fig. 2B), monocytes (r = -0.4995, Fig. 2C), and neutrophils (r = -0.5328, Figure 4 Fig. 2D). Notably, the TRIM69 levels in the serum were positively correlated with the platelet-lymphocyte ratio (PLR) related to inflammation (r = 0.5931, Fig. 2E); in terms of complement, the TRIM69 levels in the serum were negatively correlated with C3 (r = -0.7829, Fig. 2F).

[0094] In addition, the TRIM69 levels in the serum of systemic lupus erythematosus patients with specific positive autoantibodies were elevated, including anti-SSA positive systemic lupus erythematosus patients (Fig. 2G), anti-Ro52 positive systemic lupus erythematosus patients (Fig. 2H), and anti-Sm positive systemic lupus erythematosus patients (Fig. 2I), which were significantly higher than those in systemic lupus erythematosus patients with negative antibody detection results. This indicates that TRIM69 has the potential to serve as an indicator for assessing the activity and severity of systemic lupus erythematosus.

[0095] Example 4:

[0096] The serum TRIM69 levels (protein) of systemic lupus erythematosus patients, rheumatoid arthritis patients and healthy controls were detected by ELISA method, the ROC curve was drawn, and the AUC, 95% confidence interval, sensitivity and specificity were calculated.

[0097] The ROC curve analysis results are shown in Figure 4 As shown in the results, the serum TRIM69 level has potential value in distinguishing systemic lupus erythematosus patients from healthy controls, with an AUC of 0.787, a 95% confidence interval of 0.628-0.842, and an optimal cutoff value of 187.2 pg / ml, corresponding to a sensitivity of 75.00% and a specificity of 70.83% (A in FIG. 3), that is, when the concentration of TRIM69 protein in serum is >187.2 pg / ml, it can assist in diagnosing the subject as a systemic lupus erythematosus patient. In addition, the serum TRIM69 level of systemic lupus erythematosus patients is significantly higher than that of healthy controls and rheumatoid arthritis patients. Based on this, risk score analysis was performed using TRIM69 to compare systemic lupus erythematosus patients with rheumatoid arthritis patients + healthy controls, with an AUC of 0.739, a 95% confidence interval of 0.602-0.763, a sensitivity of 68.80%, and a specificity of 70.83% (B in FIG. 3). This indicates that TRIM69 has a sensitivity and specificity that is clinically useful as a diagnostic biomarker for systemic lupus erythematosus.

[0098] Example 5:

[0099] The serum TRIM69 level (protein) was combined with the routine clinical indicators hemoglobin, neutrophil to lymphocyte ratio and lymphocyte to monocyte ratio to construct a prediction model, and single factor and multiple factor analysis was performed, as shown in Table 2; the serum TRIM69 level was combined with red blood cell count and lymphocyte to monocyte ratio to construct a prediction model, and single factor and multiple factor analysis was performed, as shown in Table 3.

[0100] Table 2 Single factor and multiple factor analysis of risk factors associated with systemic lupus erythematosus 1

[0101]

[0102] Table 3 Single factor and multiple factor analysis of risk factors associated with systemic lupus erythematosus 2

[0103]

[0104] The serum TRIM69 level, hemoglobin and neutrophil to lymphocyte ratio were determined to be the best model variables, and the prediction model formula established therefrom is represented as: , the predicted value Q is calculated, wherein: Q is the predicted value, HGB is hemoglobin (g / L), NLR is the neutrophil-to-lymphocyte ratio, and TRIM69 is the expression of the protein (pg / mL).

[0105] The analysis results of the prediction model constructed by the serum TRIM69 level, hemoglobin, and neutrophil-to-lymphocyte ratio are shown in Figure 4 . The results show that: the higher the predicted value, the higher the risk of systemic lupus erythematosus (A in Figure 4 ); the prediction model performs well in distinguishing systemic lupus erythematosus patients from healthy controls, with an AUC value of 0.941 and a 95% confidence interval of 0.846-0.975, significantly better than a single indicator (B in Figure 4 ); notably, the best cutoff value of the prediction model is 0.324, which has high specificity (81.94%) and high sensitivity (93.55%) according to Graphpad prism 10.1.2 software analysis, i.e., when the predicted value is >0.324, the subject can be diagnosed as a systemic lupus erythematosus patient. Similarly, the prediction model can distinguish systemic lupus erythematosus patients from rheumatoid arthritis patients + healthy controls (C in Figure 5 ), with an AUC value of 0.805 and a 95% confidence interval of 0.691-0.836, and the best cutoff value is 1.558, corresponding to a sensitivity of 77.17% and a specificity of 72.22% (D in Figure 5 ), i.e., when the predicted value is >1.558, it can assist in diagnosing the subject as a systemic lupus erythematosus patient.

[0106] A disease prediction model is constructed by the serum TRIM69 level and the red blood cell count and the lymphocyte-to-monocyte ratio, as shown in Figure 5 . The results show that: there is a statistical difference in the predicted value between systemic lupus erythematosus patients and healthy controls (A in Figure 5 ), but it cannot distinguish between systemic lupus erythematosus patients and rheumatoid arthritis patients + healthy controls (B in Figure 6 ); and it performs generally in distinguishing systemic lupus erythematosus patients from healthy controls, with an AUC value of 0.605 and a 95% confidence interval of 0.510-0.701 (C in Figure 6 ), and the cutoff value is 5.212, with high sensitivity (85.48%) but low specificity (38.89%) according to Graphpad prism 10.1.2 software analysis.

[0107] Example 6:

[0108] The relationship between the prediction model constructed by the serum TRIM69 level, hemoglobin and neutrophil-to-lymphocyte ratio and the clinical characteristics of the patients with systemic lupus erythematosus was analyzed. The analysis covered the systemic lupus erythematosus disease activity index, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and complete blood count and other indicators.

[0109] The analysis results of the relationship between the prediction model constructed by the serum TRIM69 level, hemoglobin and neutrophil-to-lymphocyte ratio and the clinical characteristics of the patients with systemic lupus erythematosus are shown in ​ The results show that the predicted value calculated by the prediction model is significantly correlated with the systemic lupus erythematosus disease activity. The specific correlation is as follows: the predicted value is positively correlated with the percentage of neutrophils (r = 0.4325, A in FIG. 6), the predicted value is positively correlated with the platelet-to-lymphocyte ratio (r = 0.5555, B in FIG. 6), and the predicted value is strongly positively correlated with the neutrophil-to-lymphocyte ratio (r = 0.7229, C in FIG. 6); in addition, the predicted value is negatively correlated with red blood cells (r = -0.418, D in FIG. 6), the predicted value is negatively correlated with hemoglobin (r = -0.5374, E in FIG. 6), the predicted value is negatively correlated with hematocrit (r = -0.5243, F in FIG. 6), the predicted value is negatively correlated with lymphocytes (r = -0.592, G in FIG. 6), the predicted value is negatively correlated with the percentage of lymphocytes (r = -0.6205, ​ H in FIG. 6), and the predicted value is negatively correlated with the lymphocyte-to-monocyte ratio (r = -0.3295, I in FIG. 6). This indicates that the prediction model constructed by the serum TRIM69 level, hemoglobin and neutrophil-to-lymphocyte ratio has application value in evaluating the systemic lupus erythematosus disease activity.

[0110] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement and improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. Use of a reagent for detecting the concentration of TRIM69 protein in the preparation of a kit for aiding in the diagnosis of systemic lupus erythematosus.

2. Use according to claim 1, characterized in that: The reagent for detecting the concentration of TRIM69 protein comprises an antibody for detecting TRIM69 protein.

3. Use according to claim 2, wherein: The biological sample detected by the kit comprises peripheral blood or serum.

4. Use according to claim 3, wherein: When the kit detects the concentration of TRIM69 protein in the serum of the subject by ELISA method > 187.2 pg / ml, it aids in the diagnosis of the subject as a systemic lupus erythematosus patient, wherein the subject does not include a rheumatoid arthritis patient.

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