A biomarker for assisting diagnosis of systemic lupus erythematosus and application thereof

Abstract

The application provides a biomarker for assisting in diagnosing systemic lupus erythematosus and application thereof, proves that 15(S)-HETE has good diagnostic efficiency for systemic lupus erythematosus, and the diagnostic efficiency is improved after 15(S)-HETE is combined with anti-dsDNA antibody or anti-Smith antibody, has good diagnostic efficiency for systemic lupus erythematosus with negative specific autoantibody, and 15(S)-HETE can also reflect the disease activity of systemic lupus erythematosus.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to a biomarker for the auxiliary diagnosis of systemic lupus erythematosus and its application. Background Technology

[0002] Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterized by multi-system and multi-organ involvement with varying degrees of involvement. It has a high rate of disability and mortality, imposing a heavy disease burden on patients and society.

[0003] In terms of diagnosis, no biomarkers with both high sensitivity and specificity have yet been discovered, leading to high rates of misdiagnosis and missed diagnosis. Currently, clinical diagnosis of SLE routinely involves detecting serum anti-dsDNA antibodies and anti-Smith antibodies. Both of these indicators are specific antibodies for diagnosing lupus, exhibiting good specificity but poor sensitivity; a significant proportion of SLE patients do not test positive for these two autoantibodies. Therefore, there is an urgent need to discover novel biomarkers to aid in the diagnosis of SLE and improve diagnostic efficacy.

[0004] SLE is a long and recurrent disease, necessitating the development of indicators that monitor disease activity for timely and accurate patient assessment. Existing diagnostic indicators, such as serum anti-Smith antibodies, show weak correlation with SLE disease activity. Therefore, there is an urgent need to discover novel biomarkers that are closely related to SLE disease activity to optimize SLE disease monitoring. Summary of the Invention

[0005] In view of this, in order to overcome the shortcomings of the prior art, the present invention is proposed.

[0006] The first aspect of the present invention provides the use of reagents for detecting biomarkers in the preparation of products for diagnosing systemic lupus erythematosus, said biomarkers including 15(S)-HETE.

[0007] In this invention, the term "diagnosis" refers to the discovery, judgment, or cognition of an individual's health status or condition based on one or more symptoms, data, or other information related to the individual.

[0008] In this invention, 15(S)-HETE is officially called 15(S)-Hydroxyeicosatetraenoic acid, which is a bioactive lipid molecule produced by the metabolism of arachidonic acid.

[0009] In some implementations, the 15(S)-HETE is expressed at significantly low levels in patients with systemic lupus erythematosus.

[0010] In some embodiments, the biomarker also includes serum complement, which can be used as a complementary reference to serum complement concentration.

[0011] In this invention, the systemic lupus erythematosus includes systemic lupus erythematosus with positive specific autoantibodies and systemic lupus erythematosus with negative specific autoantibodies.

[0012] In some implementations, the specific autoantibody includes anti-dsDNA antibody and anti-Smith antibody.

[0013] In one specific implementation, the systemic lupus erythematosus (SLE) is selected from SLE that is negative for specific autoantibodies. SLE that is negative for specific autoantibodies includes SLE that is negative for both anti-dsDNA antibodies and anti-Smith antibodies. When SLE is SLE that is negative for specific autoantibodies, 15(S)-HETE alone is effective in diagnosing SLE, and the expression level of 15(S)-HETE is reduced in SLE that is negative for specific autoantibodies compared to healthy subjects.

[0014] In some embodiments, the systemic lupus erythematosus (SLE) is selected from SLE that is positive for specific autoantibodies. SLE that is positive for specific autoantibodies includes SLE that is positive only for anti-dsDNA antibodies, SLE that is positive only for anti-Smith antibodies, and SLE that is positive for both anti-dsDNA and anti-Smith antibodies. When the SLE is SLE that is positive for specific autoantibodies, the biomarker also includes specific autoantibodies, such as one or more of anti-dsDNA antibodies and anti-Smith antibodies. 15(S)-HETE can be used alone to diagnose SLE, or 15(S)-HETE can be used in combination with anti-dsDNA antibodies and / or anti-Smith antibodies. Compared to healthy subjects, 15(S)-HETE expression levels are decreased in SLE that is positive for specific autoantibodies, while anti-dsDNA antibody and / or anti-Smith antibody expression levels are increased.

[0015] In one specific implementation, when systemic lupus erythematosus is systemic lupus erythematosus that is positive for specific autoantibodies, 15(S)-HETE combined with anti-dsDNA antibody or 15(S)-HETE combined with anti-Smith antibody is used to diagnose systemic lupus erythematosus.

[0016] In this invention, the product determines whether a subject has systemic lupus erythematosus by measuring the expression levels of biomarkers in a sample.

[0017] In some implementations, the sample is derived from a human or a non-human mammal.

[0018] In some implementations, the samples include, but are not limited to, tissues, blood, plasma, serum, saliva, urine, intestinal excrement, cerebrospinal fluid, sputum, sweat, breast milk, tears, bile, gastric juice, interstitial fluid, oral or nasal swabs, aqueous humor, amniotic fluid, and pleural fluid.

[0019] In one specific implementation, the sample is selected from serum.

[0020] In some implementations, the reagents include, but are not limited to, probes, aptamers, or binding proteins that are specific to the detection of biomarkers.

[0021] In some embodiments, the reagent further includes a detectable marker. Suitable detectable markers include, but are not limited to, radioisotopes, nucleotide chromophores, enzymes, substrates, fluorescent molecules, chemiluminescent components, magnetic particles, and bioluminescent components. Therefore, the marker is any composition detectable by a device or method, including but not limited to spectroscopic, photochemical, biochemical, immunochemical, electrical, optical, chemical detection devices, or any other suitable device. Furthermore, the marker can be visually detected without the aid of a device.

[0022] In this invention, radioactive isotopes include, but are not limited to, those mentioned above. 3 H, 14 C 35 S, 125 I, 131 I. Enzymes include, but are not limited to, horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase, and acetylcholinesterase. Fluorescent molecules include, but are not limited to, FITC, rhodamine, and lanthanide phosphors.

[0023] In this invention, the term "probe" refers to a molecule capable of binding to a specific sequence, subsequence, or other portion of another molecule. In this invention, the probe specifically binds to a biomarker.

[0024] In some embodiments, the probe can specifically bind to 15(S)-HETE, anti-dsDNA antibodies, and anti-Smith antibodies. For example, probes labeled with fluorescent molecules or quantum dots can specifically bind to lipids or embed in lipid structures (such as cell membranes); for example, probes can specifically recognize and bind to target proteins (anti-dsDNA antibodies, anti-Smith antibodies), thereby enabling the detection of protein expression levels or states of presence.

[0025] In this invention, the term "aptamer" refers to a single-stranded DNA or RNA molecule (typically 20-80 nucleotides long) selected by the Systematic Evolution of Ligands with Exponential Enrichment (SELEX) technique, which can fold into a specific three-dimensional structure and bind biomarkers 15(S)-HETE, anti-dsDNA antibodies, and / or anti-Smith antibodies with high specificity through conformational matching or charge complementarity.

[0026] In this invention, the term "binding protein" refers to a protein that specifically binds to a biomarker. When the biomarker is 15(S)-HETE, the binding protein can be a specific antibody against 15(S)-HETE. When the biomarker includes anti-dsDNA antibody or anti-Smith antibody, the binding protein can be a specific antibody against anti-dsDNA antibody or anti-Smith antibody, or it can be an antigen that can bind to anti-dsDNA antibody or anti-Smith antibody.

[0027] The antibodies in this invention include polyclonal or monoclonal antibodies, antibody fragments (such as Fab, Fab', F(ab')2 and Fv fragments), single-chain Fv (scFv) antibodies, multispecific antibodies (such as bispecific antibodies), monospecific antibodies, monovalent antibodies, chimeric antibodies, humanized antibodies, human antibodies, fusion proteins containing antigen-binding sites of antibodies, and any other modified immunoglobulin molecules containing antigen-binding sites, provided that the antibody exhibits the desired biobinding activity.

[0028] In some implementations, the products for diagnosing systemic lupus erythematosus include, but are not limited to, kits, chips, test strips, risk prediction models, or risk assessment systems.

[0029] A second aspect of the present invention provides the use of reagents for detecting biomarkers in the preparation of products for diagnosing the disease activity of systemic lupus erythematosus, said biomarkers including 15(S)-HETE.

[0030] In some implementations, the biomarker also includes serum complement.

[0031] In some implementations, the reagents include, but are not limited to, probes, aptamers, or binding proteins that are specific to the detection of biomarkers.

[0032] In some implementations, the products used to diagnose systemic lupus erythematosus disease activity include, but are not limited to, kits, chips, test strips, risk prediction models, or risk assessment systems.

[0033] In some implementations, the systemic lupus erythematosus includes systemic lupus erythematosus that is positive for specific autoantibodies and systemic lupus erythematosus that is negative for specific autoantibodies.

[0034] In some implementations, the specific autoantibody includes anti-dsDNA antibody and anti-Smith antibody.

[0035] In some implementations, the systemic lupus erythematosus is selected from systemic lupus erythematosus that is negative for specific autoantibodies.

[0036] The third aspect of the present invention provides any of the following products:

[0037] (1) A product for diagnosing systemic lupus erythematosus, the product comprising a reagent for detecting a biomarker, the biomarker comprising 15(S)-HETE;

[0038] In some implementations, the biomarker further includes one or more of anti-dsDNA antibodies and anti-Smith antibodies;

[0039] In some embodiments, the reagents include, but are not limited to, probes, aptamers, or binding proteins that are specific to the detection of biomarkers;

[0040] In some implementations, the products for diagnosing systemic lupus erythematosus include, but are not limited to, kits, chips, test strips, risk prediction models, or risk assessment systems.

[0041] In some implementations, the systemic lupus erythematosus includes systemic lupus erythematosus that is positive for specific autoantibodies and systemic lupus erythematosus that is negative for specific autoantibodies;

[0042] In some embodiments, the systemic lupus erythematosus is selected from systemic lupus erythematosus that is negative for specific autoantibodies;

[0043] (2) A product for diagnosing the disease activity of systemic lupus erythematosus, the product comprising a reagent for detecting a biomarker, the biomarker comprising 15(S)-HETE.

[0044] In some implementations, the reagents include, but are not limited to, probes, aptamers, or binding proteins that are specific to the detection of biomarkers.

[0045] In some implementations, the products used to diagnose systemic lupus erythematosus disease activity include, but are not limited to, kits, chips, test strips, risk prediction models, or risk assessment systems.

[0046] In some implementations, the systemic lupus erythematosus includes systemic lupus erythematosus that is positive for specific autoantibodies and systemic lupus erythematosus that is negative for specific autoantibodies.

[0047] In some implementations, the systemic lupus erythematosus is selected from systemic lupus erythematosus that is negative for specific autoantibodies.

[0048] The fourth aspect of the present invention provides any of the following systems:

[0049] (1) A system for predicting systemic lupus erythematosus using biomarkers, comprising:

[0050] A data acquisition unit is used to acquire data on biomarkers of the target subject, wherein the biomarkers include 15(S)-HETE;

[0051] Result determination unit: used to compare the biomarker data obtained by the data acquisition unit with a pre-set threshold to determine whether the target subject has systemic lupus erythematosus;

[0052] Result output unit: Outputs the judgment result of the result judgment unit;

[0053] In some implementations, the biomarker further includes specific autoantibodies;

[0054] In some embodiments, the specific autoantibody includes one or more of anti-dsDNA antibodies and anti-Smith antibodies;

[0055] In some implementations, the systemic lupus erythematosus includes systemic lupus erythematosus that is positive for specific autoantibodies and systemic lupus erythematosus that is negative for specific autoantibodies;

[0056] In some embodiments, the systemic lupus erythematosus is selected from systemic lupus erythematosus that is negative for specific autoantibodies;

[0057] (2) A system for predicting systemic lupus erythematosus disease activity using biomarkers, comprising:

[0058] A data acquisition unit is used to acquire data on biomarkers of the target subject, wherein the biomarkers include 15(S)-HETE;

[0059] Result determination unit: used to compare the biomarker data obtained by the data acquisition unit with a pre-set threshold to determine the disease activity of systemic lupus erythematosus in the target subject;

[0060] Result Output Unit: Outputs the judgment result of the result judgment unit.

[0061] The fifth aspect of the present invention provides a computer-aided prediction device, comprising:

[0062] The system includes a memory for storing program instructions and a processor for calling program instructions. When the program instructions are executed, they implement the unit functions of the system described in the fourth aspect of the present invention.

[0063] The sixth aspect of the present invention provides a computer-readable storage medium on which a computer program is stored, and when the computer program is executed by a processor, it implements the unit functions of the system described in the fourth aspect of the present invention.

[0064] The advantages and beneficial effects of this invention are as follows:

[0065] This invention provides a biomarker for the auxiliary diagnosis of systemic lupus erythematosus (SLE) and its application. The present invention is convenient to sample, requires a small blood volume, and can be performed during routine blood tests. This invention demonstrates that 15(S)-HETE has good diagnostic efficacy for SLE, and that the diagnostic efficacy is further improved when 15(S)-HETE is combined with anti-dsDNA antibodies or anti-Smith antibodies. It also shows good diagnostic efficacy for SLE that is negative for specific autoantibodies. Furthermore, 15(S)-HETE can reflect the disease activity of SLE. Attached Figure Description

[0066] Figure 1 This is a graph showing the concentration of 15(S)-HETE in the serum of SLE patients.

[0067] Figure 2 This is a graph showing the serum 15(S)-HETE concentration results in SLE patients with different erythrocyte sedimentation rate (ESR) concentrations.

[0068] Figure 3 This is a graph showing the correlation between serum IgG concentration and 15(S)-HETE concentration in SLE patients.

[0069] Figure 4 This is a graph showing the correlation between peripheral blood leukocyte count and 15(S)-HETE concentration in SLE patients.

[0070] Figure 5 This is a graph showing the correlation between the number of peripheral blood neutrophils and the concentration of 15(S)-HETE in SLE patients.

[0071] Figure 6 The ROC curves for training concentrations of anti-dsDNA antibody, serum 15(S)-HETE, and anti-dsDNA antibody combined with serum 15(S)-HETE in the diagnosis of systemic lupus erythematosus are shown.

[0072] Figure 7 The ROC curves are used to verify the diagnostic efficacy of concentrated anti-dsDNA antibody, serum 15(S)-HETE, and anti-dsDNA antibody combined with serum 15(S)-HETE for systemic lupus erythematosus.

[0073] Figure 8The ROC curves for training concentrations of anti-Smith antibody, serum 15(S)-HETE, and anti-Smith antibody combined with serum 15(S)-HETE in the diagnosis of systemic lupus erythematosus are shown.

[0074] Figure 9 The ROC curves are used to verify the diagnosis of systemic lupus erythematosus by concentrated anti-Smith antibody, serum 15(S)-HETE, and anti-Smith antibody combined with serum 15(S)-HETE.

[0075] Figure 10 This is a graph showing the difference in expression of 15(S)-HETE between patients with systemic lupus erythematosus who were negative for specific autoantibodies and healthy controls;

[0076] Figure 11 This is the ROC curve for 15(S)-HETE diagnosis of systemic lupus erythematosus in patients with negative specific autoantibodies. Detailed Implementation

[0077] The present invention will be described below with reference to some embodiments. These descriptions are merely preferred embodiments of the present invention and are not intended to limit the invention in any other way. Any person skilled in the art may make equivalent modifications to the disclosed technical content to create equivalent embodiments. Any simple modifications or equivalent changes made to the following embodiments based on the technical essence of the present invention without departing from the scope of the invention are all within the protection scope of the present invention.

[0078] Example 1

[0079] (1) Subject enrollment:

[0080] Inclusion criteria for the healthy control group: Healthy individuals aged 18-65 years, regardless of gender;

[0081] Exclusion criteria: Subjects cannot be selected if they meet any of the following conditions:

[0082] a) Healthy controls who have taken antibiotics, anticonvulsants, or had gastroenteritis in the past month;

[0083] b) Recently diagnosed with serious underlying diseases such as infectious diseases, malignant tumors, leukemia, acute heart failure, or acute coronary syndrome;

[0084] c) Symptoms or signs of severe, progressive, or uncontrolled kidney, liver, blood, gastrointestinal, endocrine, lung, heart, neurological, psychiatric, or brain disease;

[0085] d) To perform organ transplantation surgery;

[0086] e) Women who are pregnant.

[0087] SLE patient inclusion criteria: meeting the 2019 SLE classification diagnostic criteria of the European Alliance of Associations for Rheumatology (EULAR) / American College of Rheumatology (ACR), and not having taken glucocorticoids or immunosuppressants within the past three months;

[0088] Exclusion criteria: Those with chronic or acute infections or serious underlying diseases.

[0089] Inclusion criteria for patients with rheumatoid arthritis (RA): meeting the diagnostic criteria for RA classification in ACR / EULAR 2010 and not having taken glucocorticoids or immunosuppressants within the past three months;

[0090] Exclusion criteria: Those with chronic or acute infections or serious underlying diseases.

[0091] (2) Serum collection:

[0092] Peripheral blood was collected from healthy controls (N=24), SLE patients (N=52), and disease controls (RA patients (N=24) via antecubital vein puncture using a coagulation-promoting tube. The blood was centrifuged (3000 rpm, 10 minutes, 4 degrees Celsius), and the supernatant pale yellow liquid was collected as serum. The serum was aliquoted and stored at -80 degrees Celsius for subsequent testing.

[0093] (3) Enzyme-linked immunosorbent assay (ELISA):

[0094] The serum to be tested should be shaken and mixed well, then diluted 10 times with the Assay Buffer in the kit (Enzo Life Sciences, ADI-900-051). Take 100 μL of diluted serum for testing, perform the experiment according to the kit instructions, and calculate the concentration of 15(S)-HETE in the serum before dilution according to the method in the instructions.

[0095] (4) Using Prism 10 software, the concentrations of 15(S)-HETE in peripheral blood serum of healthy controls, SLE patients and RA patients were compared by one-way ANOVA and a statistical graph was generated.

[0096] The results are as follows Figure 1As shown, compared with healthy controls, the concentration of 15(S)-HETE in the serum of SLE patients was significantly decreased, which was statistically significant. However, in another common autoimmune disease, RA, the concentration of serum 15(S)-HETE did not decrease significantly, suggesting that the decrease in the concentration of 15(S)-HETE in the serum of SLE patients is disease-specific.

[0097] Example 2

[0098] Based on Example 1, further clinical diagnosis and treatment information of the subjects was collected and correlated with the serum 15(S)-HETE concentration measured above.

[0099] An elevated erythrocyte sedimentation rate (ESR) indicates SLE disease activity. SLE patients with an ESR higher than 30 mm / hr were classified as having high disease activity, while those with an ESR lower than 30 mm / hr were classified as having low disease activity. Comparing serum 15(S)-HETE concentrations between the two groups revealed a significant decrease in serum 15(S)-HETE concentrations in patients with high disease activity. Figure 2 ).

[0100] Serum IgG levels are elevated in SLE patients during disease activity. Correlation analysis revealed a significant negative correlation between serum IgG concentration and 15(S)-HETE concentration in SLE patients (P=0.0182, R0). 2 =0.1086) Figure 3 ).

[0101] Leukopenia is a common clinical manifestation of SLE. Neutrophil count in SLE patients is significantly negatively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and neutrophil counts significantly recover after treatment, indicating that decreased white blood cell and neutrophil counts can suggest SLE disease activity. Correlation analysis revealed a significant positive correlation between peripheral blood white blood cell count and 15(S)-HETE concentration in SLE patients (P=0.0123, R0.05). 2 =0.1188), and the peripheral blood neutrophil count in SLE patients was also significantly positively correlated with the 15(S)-HETE concentration (P=0.0406, R=0.1188). 2 =0.0812) Figures 4-5 ).

[0102] In summary, serum 15(S)-HETE concentration in SLE patients is significantly correlated with multiple disease activity indicators, and decreased serum 15(S)-HETE concentration may indicate disease activity.

[0103] Example 3

[0104] The subjects were divided into a training set and a validation set in a 1:1 ratio. The diagnostic efficacy of serum 15(S)-HETE concentration combined with autoantibodies for SLE was studied in both the training and validation sets: ROC curves were plotted using SPSS software.

[0105] In the training set, the AUC of anti-dsDNA antibody in the SLE group was 0.620, the AUC of serum 15(S)-HETE concentration was 0.666, and the AUC of anti-dsDNA antibody combined with serum 15(S)-HETE concentration was 0.712. Figure 6 Simultaneously, analysis revealed that the AUC of anti-Smith antibody in the SLE group was 0.620, the AUC of serum 15(S)-HETE concentration was 0.666, and the AUC of anti-Smith antibody combined with serum 15(S)-HETE concentration was 0.793. Figure 8 ).

[0106] In the validation set, the AUC of anti-dsDNA antibody in the SLE group was 0.580, the AUC of serum 15(S)-HETE concentration was 0.672, and the AUC of anti-dsDNA antibody combined with serum 15(S)-HETE concentration was 0.755. Figure 7 Simultaneously, analysis revealed that the AUC of anti-Smith antibody in the SLE group was 0.620, the AUC of serum 15(S)-HETE concentration was 0.672, and the AUC of anti-Smith antibody combined with serum 15(S)-HETE concentration was 0.749. Figure 9 The results suggest that serum 15(S)-HETE concentration can be used as an auxiliary diagnostic tool for SLE, significantly improving the diagnostic efficacy of two routinely tested indicators: anti-dsDNA antibody and anti-Smith antibody.

[0107] Example 4

[0108] A significant proportion of SLE patients test negative for both anti-Smith antibodies and anti-dsDNA antibodies, posing a major challenge to the clinical diagnosis of SLE.

[0109] We screened SLE patients (N=4) who were negative for both anti-Smith antibody and anti-dsDNA antibody to investigate whether serum 15(S)-HETE concentration could be used to diagnose this group of SLE patients who were negative for specific autoantibodies. The study found that compared with healthy controls (N=4), the serum 15(S)-HETE concentration in SLE patients who were negative for specific autoantibodies was significantly lower, which was statistically significant. Figure 10 ).

[0110] Another 20 healthy subjects were screened, and 26 patients (N=26) who were negative for both anti-Smith antibody and anti-dsDNA antibody were selected from the SLE subjects to verify the diagnostic efficacy of serum 15(S)-HETE concentration in SLE patients who were negative for specific autoantibodies. ROC curve analysis showed that the AUC was 0.7000, which was statistically significant (P=0.0212). Figure 11 The decrease in serum 15(S)-HETE concentration can serve as a relatively specific auxiliary reference indicator for diagnosing SLE patients who are negative for specific autoantibodies.

[0111] The above description of the embodiments is only for understanding the method and core ideas of the present invention. It should be noted that those skilled in the art can make various improvements and modifications to the present invention without departing from the principles of the invention, and these improvements and modifications will also fall within the protection scope of the claims of the present invention.

Claims

1. The application of reagents for detecting biomarkers in the preparation of products for diagnosing systemic lupus erythematosus, characterized in that, The biomarkers include 15(S)-HETE and anti-dsDNA antibody, and the reagents include binding proteins that specifically detect the biomarkers.

2. The application of reagents for detecting biomarkers in the preparation of products for diagnosing systemic lupus erythematosus, characterized in that, The biomarkers include 15(S)-HETE and anti-Smith antibody, and the reagents include binding proteins that specifically detect the biomarkers.

3. The application of reagents for detecting biomarkers in the preparation of products for diagnosing systemic lupus erythematosus, characterized in that, The biomarker includes 15(S)-HETE, and the systemic lupus erythematosus is a systemic lupus erythematosus that is negative for specific autoantibodies; the specific autoantibodies include anti-dsDNA antibodies and anti-Smith antibodies, and the reagent includes a binding protein that detects the specificity of the biomarker.

4. The application according to any one of claims 1-3, characterized in that, The product determines whether a subject has systemic lupus erythematosus by measuring the expression levels of biomarkers in a sample.

5. The application according to claim 4, characterized in that, The sample was selected from serum.

6. The application according to any one of claims 1-3, characterized in that, The products used to diagnose systemic lupus erythematosus include reagent kits, chips, test strips, or risk assessment systems.

7. A system for predicting systemic lupus erythematosus using biomarkers, characterized in that, include: A data acquisition unit is used to acquire data on biomarkers of the target subject, including 15(S)-HETE and anti-dsDNA antibody; Result determination unit: used to compare the biomarker data obtained by the data acquisition unit with a pre-set threshold to determine whether the target subject has systemic lupus erythematosus; Result Output Unit: Outputs the judgment result of the result judgment unit.

8. A system for predicting systemic lupus erythematosus using biomarkers, characterized in that, include: A data acquisition unit is used to acquire data on biomarkers of the target subject, including 15(S)-HETE and anti-Smith antibody; Result determination unit: used to compare the biomarker data obtained by the data acquisition unit with a pre-set threshold to determine whether the target subject has systemic lupus erythematosus; Result Output Unit: Outputs the judgment result of the result judgment unit.

9. A system for predicting systemic lupus erythematosus using biomarkers, characterized in that, include: A data acquisition unit is used to acquire data on biomarkers of the target subject, wherein the biomarkers include 15(S)-HETE; Result determination unit: used to compare the biomarker data obtained by the data acquisition unit with a pre-set threshold to determine whether the target subject has systemic lupus erythematosus; Result output unit: Outputs the judgment result of the result judgment unit; The systemic lupus erythematosus (SLE) is selected from SLE that is negative for specific autoantibodies; the specific autoantibodies include anti-dsDNA antibodies and anti-Smith antibodies.

10. A computer-aided prediction device, characterized in that, include: A memory and a processor, wherein the memory is used to store program instructions, and the processor is used to invoke the program instructions, and when the program instructions are executed, to implement the unit functions of the system according to any one of claims 7-9.

11. A computer-readable storage medium storing a computer program that, when executed by a processor, performs the unit functions of the system according to any one of claims 7-9.

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