Marker, system and kit for screening or diagnosing behcet disease and application of marker, system and kit

Abstract

The invention relates to a marker, a system and a kit for screening or diagnosing behcet disease and application of the marker, the system and the kit. The marker is an IgG4 protein which is specifically combined with erythrina indica lectin and has a glycosylation structure. The IgG4 protein specifically recognized and combined with ECL, especially the IgG4 protein containing Galbeta4GlcNAc and other special glycosylation structures, is obviously reduced in BD patients, and the IgG4 protein specifically combined with erythrina indica lectin and having the glycosylation structure is used as a marker, so that the BD patients or the BD suffering risk can be more rapidly and accurately judged clinically; powerful technical support is provided for clinical treatment or prevention of Behcet's disease, and a foundation is laid for research on related mechanisms of Behcet's disease.

Description

Technical Field

[0001] The present disclosure relates to the field of biotechnology, and in particular, to a marker, system, and kit for screening or diagnosing Behçet's disease, and uses thereof. Background Art

[0002] Behçet's disease (BD) is a multisystem chronic vasculitis of unknown etiology. BD is highly heterogeneous, with complex and variable clinical manifestations. Patients often experience recurrent oral ulcers, genital ulcers, and skin lesions. Early diagnosis of BD remains difficult, relying primarily on clinicians' symptom assessment and evaluation, which often leads to delayed diagnosis.

[0003] Glycosylation is a common translational modification that regulates numerous biological processes, including protein folding, stability, and host-pathogen interactions. The effector functions of immunoglobulins (Igs) are largely determined by their glycosylation structures. In addition to quantitative variations in specific Ig isotypes, Ig N-glycosylation plays a crucial role in regulating the functional interactions between Igs and receptors and other interacting molecules. Glycosylation plays a crucial role in immune homeostasis, immune regulation, and the effector functions of antibodies. Studies have reported that for IgG, subclass-specific structural differences and Fc glycosylation influence affinity for FcγRs. Lactosylated IgG has significantly increased affinity for activating FcRs. In addition to lactosylated N-glycans, IgG glycans containing fucose and sialic acid also influence Ig binding affinity for their Fc receptors. Furthermore, antibody glycosylation can influence antibody function by altering the structure of the Ig Fc fragment or by controlling the recruitment of effector cells that bind to specific Fc receptors.

[0004] In terms of inflammation, specific glycoforms on IgG are associated with different functions. Sialylation of the galactosylated N297 glycan affects the conformation of the antibody, thereby altering the interaction with the receptor and downstream anti-inflammatory signaling pathways. IgG without galactosylation is considered a pro-inflammatory antibody, and the loss of galactose leads to binding to mannan-binding lectins, thereby activating the complement pathway and participating in the pathogenesis. The distribution of immunoglobulin glycosylation and its changes among different immunoglobulin subtypes remains unclear in BD. Identifying new biomarkers is not only crucial for early diagnosis and risk assessment, but also helps to reveal the underlying pathological mechanisms. Summary of the Invention

[0005] In order to solve the above technical problems, the present disclosure provides a marker, a system, a kit and uses thereof for screening or diagnosing Behçet's disease.

[0006] In order to achieve the above objectives, the present disclosure provides, in a first aspect, a marker for screening or diagnosing Behçet's disease, wherein the marker is an IgG4 protein having a glycosylation structure that is specifically bound by Erythrina chinensis lectin.

[0007] Optionally, the glycosylation structure comprises Galβ4GlcNAc.

[0008] A second aspect of the present disclosure provides a system for screening or diagnosing Behçet's disease, the system comprising: A device for detecting the signal value of an IgG4 protein glycosylation structure lectin, a calculation device, an input device for inputting the standardized signal value of the IgG4 protein glycosylation structure lectin, and an output device for outputting the discrimination between normal subjects and Behçet's disease patients; wherein the computer device includes a memory and a processor, the memory storing a computer program, and the processor being configured to execute the computer program in the memory to implement correction calculation and standardization calculation of the IgG4 protein glycosylation structure lectin signal value, as well as Behçet's disease discrimination; The correction calculation is: the IgG4 protein glycosylation structure lectin signal value is divided by 25% of the negative control signal value of the IgG4 protein glycosylation structure lectin detection point in the Block area of ​​the detection chip to obtain the IgG4 protein glycosylation structure lectin correction signal value; The standardization calculation is as follows: dividing the IgG4 protein glycosylation structure lectin correction signal value by the IgG4 protein quantitative concentration value to obtain the IgG4 protein glycosylation structure lectin normalized signal value; The Behçet's disease is diagnosed as follows: if the ratio of the standardized signal value of the IgG4 protein glycosylation structure lectin of the patient to be tested to the standardized signal value of the IgG4 protein glycosylation structure lectin of the healthy control is greater than the judgment threshold and has a statistical difference, then the patient to be tested is determined to have Behçet's disease or to have a risk of developing Behçet's disease.

[0009] Optionally, the judgment threshold is any value greater than 1.0, preferably any value in the range of 1.2-10.0.

[0010] Optionally, the device for detecting the lectin signal value of the glycosylation structure of IgG4 protein includes an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled anti-IgG4 protein antibody, a lectin that can specifically bind to the glycosylation structure of IgG4 protein, and a chip signal reader; the glycosylation structure contains Galβ4GlcNAc; and the lectin is Erythrina chinensis lectin.

[0011] The third aspect of the present disclosure provides use of the material for detecting the signal value of IgG4 protein glycosylation structure lectin in the system described in the second aspect in preparing a kit for screening or diagnosing Behcet's disease.

[0012] Optionally, the material for detecting the signal value of the IgG4 protein glycosylation structure lectin is a material that can be detected in a human blood sample.

[0013] Optionally, the kit contains an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled anti-IgG4 protein antibody, and a lectin that can specifically bind to the IgG4 protein glycosylation structure; the lectin is Erythrina chinensis lectin.

[0014] Optionally, the kit further contains a fluorescent dye, a blocking agent, a diluent and a washing solution; the fluorescent dye is selected from at least one of Alexa Fluor® 647, Alexa Fluor® 488, Alex555 and Alex647; the blocking agent is BSA; the diluent is BSA or PBST; and the washing solution is PBST.

[0015] Optionally, the step of quantitatively detecting the IgG4 protein glycosylation structure lectin signal value comprises: S1. Obtain peripheral blood samples from patients with Behçet's disease; S2. Determine the IgG4 protein glycosylation structure lectin signal value in the peripheral blood sample.

[0016] Through the above technical solutions, the present disclosure provides a marker, system, and kit for screening or diagnosing Behçet's disease, and their uses. The specific glycosylation structures, especially those containing Galβ4GlcNAc, in IgG4 proteins specifically recognized and bound by Erythrina lectin are significantly reduced in patients with Behçet's disease. Using IgG4 proteins with glycosylation structures specifically bound by Erythrina lectin as markers can provide faster and more accurate clinical judgments on Behçet's disease or the risk of developing Behçet's disease, providing strong technical support for the clinical treatment or prevention of Behçet's disease and laying the foundation for research on the mechanisms related to Behçet's disease.

[0017] Other features and advantages of the present disclosure will be described in detail in the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The accompanying drawings are used to provide a further understanding of the present disclosure and constitute a part of the specification. Together with the following detailed description, they are used to explain the present disclosure but do not constitute a limitation of the present disclosure. In the accompanying drawings: Figure 1 This is a volcano plot of the sugar structures that are upregulated or downregulated in the plasma immunoglobulins of BD patients compared with healthy controls and disease controls. The left figure is the group comparison between BD patients and healthy controls (HC), and the right figure is the group comparison between BD patients and disease controls (DC).

[0019] Figure 2 Figure 2 is a Venn diagram of glycostructures upregulated or downregulated in plasma immunoglobulins of BD patients compared with healthy controls and disease controls.

[0020] Figure 3 is the distribution of immunoglobulin subtypes that differentially express carbohydrate structures in the BD group.

[0021] Figure 4 This is a comparison chart of IgG4 glycoforms detected by ECL / ECA in the BD group, healthy control group and disease control group.

[0022] Figure 5 It is a small sample ELISA to verify the binding strength of IgG4 protein and ECL in BD patient plasma. DETAILED DESCRIPTION

[0023] The following describes the specific embodiments of the present disclosure in detail with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present disclosure and are not intended to limit the present disclosure.

[0024] In this disclosure, the terms "Behçet's disease," "Behçet's syndrome," and "BD" are used interchangeably.

[0025] In this disclosure, the terms "Erythrina lectin", "ECL" and "ECA" may be used interchangeably.

[0026] A first aspect of the present disclosure provides a marker for screening or diagnosing Behçet's disease, wherein the marker is an IgG4 protein having a glycosylation structure that is specifically bound by Erythrina chinensis lectin.

[0027] In one embodiment of the present disclosure, the glycosylation structure comprises Galβ4GlcNAc.

[0028] In the present disclosure, the inventors of the present disclosure surprisingly discovered that the IgG4 protein specifically recognized and bound by the Erythrina lectin, especially the glycosylation structure containing Galβ4GlcNAc, etc., is significantly reduced in patients with Behçet's disease. Using the IgG4 protein with a glycosylation structure specifically bound by the Erythrina lectin as a marker can provide a faster and more accurate clinical judgment of Behçet's disease or the risk of Behçet's disease, and provide strong technical support for the clinical treatment or prevention of Behçet's disease.

[0029] A second aspect of the present disclosure provides a system for screening or diagnosing Behçet's disease, the system comprising: A device for detecting the signal value of an IgG4 protein glycosylation structure lectin, a calculation device, an input device for inputting the standardized signal value of the IgG4 protein glycosylation structure lectin, and an output device for outputting the discrimination between normal subjects and Behçet's disease patients; wherein the computer device includes a memory and a processor, the memory storing a computer program, and the processor being configured to execute the computer program in the memory to achieve the calculation of the correction and the standardization of the IgG4 protein glycosylation structure lectin signal value, as well as the discrimination of Behçet's disease; The correction calculation is as follows: the IgG4 protein glycosylation structure lectin signal value is divided by 25% of the negative control (buffer) signal value of the IgG4 protein glycosylation structure lectin detection point in the Block area of ​​the detection chip to obtain the IgG4 protein glycosylation structure lectin correction signal value; The standardization calculation is as follows: dividing the IgG4 protein glycosylation structure lectin correction signal value by the IgG4 protein quantitative concentration value to obtain the IgG4 protein glycosylation structure lectin normalized signal value; The Behçet's disease is diagnosed as follows: if the ratio of the standardized signal value of the IgG4 protein glycosylation structure lectin of the patient to be tested to the standardized signal value of the IgG4 protein glycosylation structure lectin of the healthy control is greater than the judgment threshold and has a statistical difference, then the patient to be tested is determined to have Behçet's disease or to have a risk of developing Behçet's disease.

[0030] In this disclosure, statistically significant differences refer to the results of the Mann-Whitney test. P <0.05.

[0031] According to the present disclosure, the judgment threshold is any value greater than 1.0, preferably any value in the range of 1.2-10.0, for example, it can be 1.1, 1.2, 1.3, 1.4, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0 and 10.0, or a value between any two of them.

[0032] According to the present disclosure, the device for detecting the IgG4 protein glycosylation structure lectin signal value comprises an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled anti-IgG4 protein antibody, a lectin capable of specifically binding to the IgG4 protein glycosylation structure, and a chip signal reader; Wherein, the glycosylation structure comprises Galβ4GlcNAc; and the lectin is Erythrina chinensis lectin.

[0033] The third aspect of the present disclosure provides use of the material for detecting the signal value of IgG4 protein glycosylation structure lectin in the system described in the second aspect in preparing a kit for screening or diagnosing Behcet's disease.

[0034] According to the present disclosure, the material for detecting the signal value of the IgG4 protein glycosylation structure lectin is a material that can be detected in a human blood sample.

[0035] In one embodiment of the present disclosure, the kit contains an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled anti-IgG4 protein antibody, and a lectin that can specifically bind to the IgG4 protein glycosylation structure.

[0036] In one embodiment of the present disclosure, the lectin is Erythrina chinensis lectin.

[0037] In one embodiment of the present disclosure, the kit further comprises a fluorescent dye, a blocking agent, a diluent, and a washing solution; Wherein, the fluorescent dye is selected from at least one of Alexa Fluor® 647, Alexa Fluor® 488, Alex555 and Alex647; The blocking agent is BSA (bovine serum albumin), preferably 1% BSA; The diluent is BSA or PBST, preferably 1% BSA or 0.05% PBST; the diluent is used to dilute the sample; The washing solution is PBST, preferably 0.05% PBST.

[0038] In one embodiment of the present disclosure, the step of quantitatively detecting the IgG4 protein glycosylation structure lectin signal value comprises: S1. Obtain peripheral blood samples from patients with Behçet's disease; S2. Determine the IgG4 protein glycosylation structure lectin signal value in the peripheral blood sample.

[0039] The present disclosure is described in detail below through examples. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present disclosure, and are not intended to limit the present disclosure.

[0040] In the following examples, the reagents, instruments or equipment used are all commercially available unless otherwise specified.

[0041] Example 1 This embodiment is used to illustrate blood sample collection.

[0042] Patients with Behçet's syndrome (BD group): The diagnosis was made according to the 2014 International Criteria for Behçet's Disease (ICBD) criteria or the 2009 International Study Group (ISG) criteria.

[0043] The disease control group (DC group) included patients with Takayasu arteritis (TA) diagnosed according to the 1990 American College of Rheumatology criteria for the diagnosis and classification of Takayasu arteritis (TA group). All patients with ANCA-associated vasculitis (AAV) whose diagnosis met the 1993 Chapel Hill consensus criteria for ANCA-associated vasculitis were designated the AAV group. Patients with primary Sjögren's syndrome (pSS) who met the American-European Consensus Criteria (AECG) were designated the pSS group.

[0044] Healthy control group (HC group): 30 healthy people who underwent physical examinations at the Physical Examination Center of Peking Union Medical College Hospital during the same period were included as healthy controls (HC). This group of people was defined as having normal imaging examination, laboratory examination, internal and external surgery examination results, and no history of autoimmune diseases, diabetes, cardiovascular diseases, tumors, or active infectious diseases.

[0045] Blood Sample Collection: Blood samples from all participants were first anticoagulated with EDTA and centrifuged at 12,000 rpm for 10 minutes. The upper plasma layer was collected and frozen at −80°C until use. All participants provided informed consent, and this study was approved by the Medical Ethics Committee of Peking Union Medical College Hospital (JS-2049). Detailed information on all participants is shown in Table 1.

[0046] Table 1

[0047] Example 2 This example is used to illustrate the quantification of immunoglobulins.

[0048] 1. Preparation of immunoglobulin quantitative chip: All blood samples, immunoglobulin standards and blank controls (1% BSA was used as blank control) were printed on the surface of diluted slides by a spotter, with each spot having two technical replicates.

[0049] 2. Blocking: Before the assay, the plasma chip was first blocked with 1% BSA at room temperature for 1 h on a shaker at 12 rpm in the dark.

[0050] 3. Sample addition: Detect the concentration of immunoglobulins in plasma by incubating with 100 μL / well of appropriate fluorescein-labeled detection antibody (Table 2) at room temperature in a dark-proof shaker at 12 rpm for 30 minutes.

[0051] Table 2 Detection antibodies for different immunoglobulin subtypes

[0052] 4. Washing: Wash the chip three times with 0.05% PBST in the dark, and then wash it twice with deionized water to remove unbound molecules.

[0053] 5. Chip detection: The chips were dried and the fluorescence signals were detected and analyzed using a GenePix 4300A microarray scanner (Molecular Devices, Sunnyvale, CA, USA) and GenePix Pro7 software (Molecular Devices, Sunnyvale, CA, USA).

[0054] 6. Quantification of immunoglobulins in plasma was performed using a standard curve conforming to a 4- or 5-parameter logistic model as described in Yu, X., et al., Quantifying antibody binding on protein microarrays using microarray nonlinear calibration. Biotechniques, 2013. 54(5): 257-64. The nplr package in R was used. The quantitative results are shown in Table 3.

[0055] Table 3

[0056] Example 3 This example is used to illustrate the detection of glycosylation structures in the proteome of a blood sample.

[0057] 1. Preparation before the experiment: (1) Preparation of laboratory-made lectin chip: The lectin chip was moved from -20℃ to a 4℃ refrigerator the night before the experiment. On the day of the experiment, the lectin chip was taken out 1 hour in advance and equilibrated to room temperature before use.

[0058] (2) Reagent preparation: Prepare 1% BSA and 0.05% PBST respectively, filter and store at 4°C (still need to be stored at 4°C after use).

[0059] 2. Sample chip screening: (1) Blocking: Add a fence to the chip, add 100 μL / well of 1% BSA to the chip, and block at room temperature at 12 rpm for 1 hour; (2) Sample: Plasma was centrifuged at 12,000 rpm for 10 min at 4°C, and then diluted with 1% BSA at different times according to the immunoglobulin to be detected: IgG and IgA antibody groups: the volume ratio of serum to 1% BSA was 1:100; IgG1+IgG3 antibody group: the volume ratio of serum to 1% BSA was 1:25; IgG2 and IgG4 antibody groups: the volume ratio of serum to 1% BSA was 1:25; Sample loading: Add the diluted plasma sample to the lectin chip, 100 μL / well, and incubate on a shaker at room temperature at 12 rpm for 2 h; (3) Washing: Wash three times with 0.05% PBST, 10 min each time; (4) Add fluorescent dye: Dilute donkey anti-human IgG (Fc), IgA, IgG1, IgG3, IgG2, IgG4, IgA1, and IgA2 to a final concentration of 2.5 μg / mL and dilute with 1% BSA. IgG+IgA, IgG1+IgG3, IgG2+IgG4, and IgA1+IgA2 can be grouped for detection. 100 μL / well, incubate in a shaker at 12 rpm for 1 hour at room temperature in the dark. For product information on anti-immunoglobulin secondary antibodies, please refer to Table 2 above. (5) Wash in dark: Wash with 0.05% PBST three times, 10 min each time; then wash with sterile double-distilled water twice, 2 min each time; (6) Microarray Detection: The microarray was air-dried and fluorescence signals were detected and analyzed using a GenePix 4300A microarray scanner (Molecular Devices, Sunnyvale, CA, USA) and GenePix Pro7 software (Molecular Devices, Sunnyvale, CA, USA). The scanning channels were as follows: IgG: 532; IgA, IgG3, IgG4, IgA1: 635; IgG1, IgG2, IgA2: 488.

[0060] 3. Data processing: Chip data processing: The F median signal values ​​of two technical replicates of the same lectin on the chip are averaged and used as the signal intensity of the lectin detection point. Samples missing all lectin detection signal points for a certain immunoglobulin subtype are removed. After eliminating duplicate samples, valid samples are obtained. Each lectin signal value on the chip is divided by 25% of the signal value of all buffers in the block where the detection point is located for background correction. Because the expression levels of each immunoglobulin subtype vary between different samples, each corrected signal value is divided by the quantitative concentration value of the corresponding immunoglobulin subtype of the patient for standardization, thereby eliminating differential changes in glycosylation signals caused by excessively high or low plasma immunoglobulin concentrations in the research subjects.

[0061] Statistical Analysis and Determination of BD-Associated Immunoglobulin Glycosylation: Statistical analysis of the data was performed using R 4.1.2 and Prism 9.0.2. Differentially expressed proteins between the BD group and the healthy control group and the disease control group were identified using the Man-Whitney test. The fold change of the lectin detection signal value for each immunoglobulin in the BD group compared with the healthy control group and the disease control group was calculated. Proteins with a fold change greater than 1 between the two groups were identified as BD-associated. Proteins with a fold change greater than 1.2 and a p < 0.05 were further validated in subsequent ELISA experiments.

[0062] 4. Experimental results: The BD group showed significant changes in glycosylation signal values ​​compared with the healthy control and disease control groups. Figure 1 Compared with the healthy control group and the disease control group, the sugar structures of BD plasma immunoglobulins that were up-regulated or down-regulated were shown in Figure 2 ,according to Figure 2 The Venn diagram showed that the levels of glycans bound by plasma immunoglobulins and chip lectins were significantly correlated with BD.

[0063] like Figure 3 As shown in the data, from the perspective of immunoglobulin subtypes, IgG glycan changes were the most common, accounting for 87.9% (29 / 33) of all changes. In addition, IgA and IgG1 glycan changes also occurred: IgA was elderberry agglutinin (SNA) bound to sialic acid, and IgG1 was banana agglutinin (BanLec) bound to sialic acid and urea oleifera agglutinin (UEA-I) bound to fucose.

[0064] like Figure 4 As shown, IgG4 proteins containing Galβ4GlcNAc glycosylation structures recognized by Erythrina chinensis lectin (ECL) were significantly reduced in BD. Compared with controls, the expression levels of 13 IgG glycans and one IgA glycan were altered by a fold change greater than 1.2 in BD. The fold changes in IgG4 glycoprotein expression in BD were 0.3 (compared with healthy controls, equivalent to the normalized signal value of IgG4 protein glycosylation structure lectin in BD patients / normalized signal value of IgG4 protein glycosylation structure lectin in HC group = 1 / 0.3 = 3.3) and 0.84 (compared with disease controls, equivalent to the normalized signal value of IgG4 protein glycosylation structure lectin in BD patients / normalized signal value of IgG4 protein glycosylation structure lectin in DC patients = 1 / 0.84 = 1.19).

[0065] Example 5 The IgG4 protein that specifically binds to ECL / ECA is downregulated in BD, and the fold change is significant. A large body of evidence indicates that complement plays a central role in the pathogenesis of BD, and that non- / low-galactosylated IgG has proinflammatory and cell-damaging effects, which are associated with the development and progression of immune diseases such as rheumatoid arthritis and membranous nephropathy. It is hypothesized that low-galactosylated IgG4 may be involved in the activation of complement via the lectin pathway, and thus in the development and progression of BD. Based on this, an ELISA was performed, in which plasma was coated with ECL and then incubated with HRP-labeled mouse anti-human IgG4 Fc secondary antibody. After adding TMB for color development, it was found that the binding strength of BD patient plasma to ECL was significantly enhanced ( Figure 5 ), combined with literature reports, this may indicate that the patient's plasma contains components including non / low galactosylation immunoglobulins that are prone to activate complement and promote inflammatory response.

[0066] The preferred embodiments of the present disclosure are described in detail above in conjunction with the accompanying drawings. However, the present disclosure is not limited to the specific details of the above embodiments. Within the technical concept of the present disclosure, various simple modifications can be made to the technical solutions of the present disclosure, and these simple modifications all fall within the scope of protection of the present disclosure.

[0067] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present disclosure will not further describe various possible combinations.

[0068] In addition, the various embodiments of the present disclosure may be arbitrarily combined, and as long as they do not violate the concept of the present disclosure, they should also be regarded as the contents disclosed by the present disclosure.

Claims

1. A marker for screening or diagnosis of Behçet's disease, characterized in that: The marker is an IgG4 protein with a glycosylation structure that is specifically bound by the Erythrina lectin.

2. The marker according to claim 1, wherein The glycosylation structure comprises Galβ4GlcNAc.

3. A system for screening or diagnosing Behçet's disease, characterized in that: The system comprises: A device for detecting the signal value of an IgG4 protein glycosylation structure lectin, a calculation device, an input device for inputting the standardized signal value of the IgG4 protein glycosylation structure lectin, and an output device for outputting the discrimination between normal subjects and Behçet's disease patients; wherein the computer device includes a memory and a processor, the memory storing a computer program, and the processor being configured to execute the computer program in the memory to implement correction calculation and standardization calculation of the IgG4 protein glycosylation structure lectin signal value, as well as Behçet's disease discrimination; The correction calculation is: the IgG4 protein glycosylation structure lectin signal value is divided by 25% of the negative control signal value of the IgG4 protein glycosylation structure lectin detection point in the Block area of ​​the detection chip to obtain the IgG4 protein glycosylation structure lectin correction signal value; The standardization calculation is as follows: dividing the IgG4 protein glycosylation structure lectin correction signal value by the IgG4 protein quantitative concentration value to obtain the IgG4 protein glycosylation structure lectin normalized signal value; The Behçet's disease is diagnosed as follows: if the ratio of the standardized signal value of the IgG4 protein glycosylation structure lectin of the patient to be tested to the standardized signal value of the IgG4 protein glycosylation structure lectin of the healthy control is greater than the judgment threshold and has a statistical difference, then the patient to be tested is determined to have Behçet's disease or to have a risk of developing Behçet's disease.

4. The system according to claim 3, wherein: The judgment threshold is any value greater than 1.0, preferably any value within the range of 1.2-10.

0.

5. The system according to claim 4, wherein: The device for detecting the IgG4 protein glycosylation structure lectin signal value comprises an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled anti-IgG4 protein antibody, a lectin that can specifically bind to the IgG4 protein glycosylation structure, and a chip signal reader; The glycosylation structure comprises Galβ4GlcNAc; and the lectin is Erythrina chinensis lectin.

6. Use of the material for detecting the signal value of IgG4 protein glycosylation structure lectin in the system of claim 3 in preparing a kit for screening or diagnosis of Behcet's disease.

7. The use according to claim 6, wherein The material for detecting the signal value of the IgG4 protein glycosylation structure lectin is a material that can be detected in a human blood sample.

8. The use according to claim 6, wherein The kit contains an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled anti-IgG4 protein antibody, and a lectin that can specifically bind to the IgG4 protein glycosylation structure; The lectin is Erythrina chinensis lectin.

9. The use according to claim 8, wherein The kit also contains a fluorescent dye, a blocking agent, a diluent, and a washing solution; The fluorescent dye is selected from at least one of Alexa Fluor® 647, Alexa Fluor® 488, Alex555 and Alex647; The blocking agent is BSA; The diluent is BSA or PBST; The washing solution is PBST.

10. The use according to claim 8, wherein The steps for quantitatively detecting the IgG4 protein glycosylation structure lectin signal value include: S1. Obtain peripheral blood samples from patients with Behçet's disease; S2. Determine the IgG4 protein glycosylation structure lectin signal value in the peripheral blood sample.

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