A marker, system and kit for screening or diagnosis of behcet's disease and uses thereof
By using IgG4 protein, which specifically binds to Erythrina lectin, as a biomarker, combined with a computing device, the screening or diagnosis of Behçet's disease has been improved, solving the problem of difficult early diagnosis of Behçet's disease and enabling faster and more accurate diagnosis, thus supporting clinical treatment and pathological research.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- PEKING UNION MEDICAL COLLEGE HOSPITAL
- Filing Date
- 2025-05-12
- Publication Date
- 2026-06-12
AI Technical Summary
Early diagnosis of Behçet's disease is difficult, and current technology relies on the diagnostic assessment of clinicians, leading to delays in diagnosis.
Using IgG4 protein with a glycosylated structure that specifically binds to Erythrina lectin as a marker, the presence or risk of Behçet's disease is determined by detecting the IgG4 protein glycosylated structure lectin signal value and performing correction and standardization calculations using a computing device.
It provides a faster and more accurate method for screening or diagnosing Behcet's disease, offering technical support for clinical treatment and prevention of Behcet's disease, and revealing the underlying pathological mechanisms.
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Figure CN120629582B_ABST
Abstract
Description
Technical Field
[0001] This disclosure relates to the field of biotechnology, and more specifically, to a biomarker, system, and kit for screening or diagnosing Behcet's disease, and their uses therein. Background Technology
[0002] Behçet's disease (BD) is a multisystem chronic vasculitis of unknown etiology. BD is highly heterogeneous, with complex and variable clinical manifestations, often including recurrent oral ulcers, genital ulcers, and skin lesions. Early diagnosis of BD remains challenging, relying primarily on clinicians' diagnosis and assessment of the patient's symptoms, which often leads to delays in diagnosis.
[0003] Glycosylation is a common translational modification that regulates many biological processes, including protein folding, stability, and host-pathogen interactions. The effector function of immunoglobulins largely depends on their glycosylation structure. Besides quantitative changes specific to immunoglobulin isotypes, N-glycosylation of immunoglobulins plays a crucial role in the functional regulation of interactions between immunoglobulins and receptors and other interacting molecules. Glycosylation plays an important role in immune homeostasis, immune regulation, and antibody effector function. Studies have reported that for IgG, subclass-specific structural differences and Fc glycosylation affect affinity for FcγR. Lactosylated IgG shows a significantly increased affinity for activated FcRs. In addition to lactose-free acylated N-glycans, IgG glycans containing fucose and sialic acid also affect the affinity of immunoglobulins for their Fc receptors. Furthermore, antibody glycosylation can affect antibody function by altering the structure of immunoglobulin Fc fragments or by controlling the recruitment of effector cells that bind to specific Fc receptors.
[0004] In inflammation, specific glycoforms on IgG are associated with different functions. Sialization of galactosylated N297 glycans alters receptor interactions and downstream anti-inflammatory signaling pathways by affecting antibody conformation. Galactosylation of IgG is considered a pro-inflammatory antibody; the loss of galactose leads to binding of mannan to lectins, thereby activating the complement pathway in pathogenesis. The glycosylation of immunoglobulins and the differences in their alteration among different immunoglobulin subtypes remain unclear in BD. Identifying novel biomarkers is crucial not only for early diagnosis and risk assessment but also for elucidating underlying pathological mechanisms. Summary of the Invention
[0005] To address the aforementioned technical problems, this disclosure provides a biomarker, system, and kit for screening or diagnosing Behcet's disease, as well as their uses.
[0006] To achieve the above objectives, the first aspect of this disclosure provides a biomarker for screening or diagnosing Behcet's disease, said biomarker being an IgG4 protein with a glycosylated structure that specifically binds to Erythrina lectin.
[0007] Optionally, the glycosylated structure comprises Galβ4GlcNAc.
[0008] A second aspect of this disclosure provides a system for screening or diagnosing Behçet's disease, the system comprising:
[0009] The device includes an apparatus for detecting the signal value of IgG4 protein glycosylation structure lectin, a computing device, an input device for inputting the standardized signal value of IgG4 protein glycosylation structure lectin, and an output device for outputting the distinction between normal individuals and patients with Behçet's disease; wherein the computing 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 perform correction calculation and standardization calculation of the IgG4 protein glycosylation structure lectin signal value, as well as the distinction of Behçet's disease;
[0010] The correction calculation is as follows: 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.
[0011] The standardization calculation is as follows: the IgG4 protein glycosylation structure lectin correction signal value is divided by the quantitative concentration value of IgG4 protein to obtain the IgG4 protein glycosylation structure lectin standardized signal value.
[0012] The Behçet's disease is determined as follows: if the ratio of the IgG4 protein glycosylation structure lectin standardized signal value of the patient to that of the healthy control is greater than the judgment threshold and has a statistically significant difference, then the patient is determined to have Behçet's disease or is at risk of having Behçet's disease.
[0013] Optionally, the judgment threshold is any value greater than 1.0, preferably any value in the range of 1.2-10.0.
[0014] Optionally, the device for detecting the IgG4 protein glycosylation structure lectin signal value includes an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled antibody against IgG4 protein, a lectin capable of specifically binding to the IgG4 protein glycosylation structure, and a chip signal reader; the glycosylation structure comprises Galβ4GlcNAc; and the lectin is Erythrina lectin.
[0015] This disclosure provides a third aspect of the use of materials from the system described in the second aspect for detecting IgG4 protein glycosylation structure lectin signal values in the preparation of a kit for screening or diagnosing Behcet's disease.
[0016] Optionally, the material used to detect the IgG4 protein glycosylation structure lectin signal value is a material that can be detected from human blood samples.
[0017] Optionally, the kit contains an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled antibody against IgG4 protein, and a lectin that can specifically bind to the IgG4 protein glycosylation structure; the lectin is Erythrina lectin.
[0018] Optionally, the kit further comprises 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.
[0019] Optionally, the steps for quantitatively detecting the IgG4 protein glycosylation structure lectin signal value include:
[0020] S1. Obtain peripheral blood samples from patients with Behçet's disease;
[0021] S2. Determine the IgG4 protein glycosylation structure lectin signal value in the peripheral blood sample.
[0022] Through the above technical solutions, this disclosure provides a biomarker, system, and kit for screening or diagnosing Behçet's disease, as well as their uses. The specific glycosylation structures, particularly those containing Galβ4GlcNAc, that are specifically recognized and bound by Erythrina lectin are significantly reduced in Behçet's disease patients. Using glycosylated IgG4 proteins specifically bound by Erythrina lectin as biomarkers can enable faster and more accurate clinical assessment of Behçet's disease or risk of developing it, providing strong technical support for clinical treatment or prevention of Behçet's disease and laying the foundation for research into the mechanisms related to Behçet's disease.
[0023] Other features and advantages of this disclosure will be described in detail in the following detailed description section. Attached Figure Description
[0024] The accompanying drawings are provided to further illustrate the present disclosure and form part of the specification. They are used together with the following detailed description to explain the present disclosure, but do not constitute a limitation thereof. In the drawings:
[0025] Figure 1This is a volcano diagram of the sugar structures of plasma immunoglobulin upregulated or downregulated expression in BD patients compared to healthy controls and disease controls. The left figure shows the intergroup comparison between BD patients and healthy controls (HC), and the right figure shows the intergroup comparison between BD patients and disease controls (DC).
[0026] Figure 2 This is a Venn diagram showing the sugar structure of upregulated or downregulated plasma immunoglobulin expression in BD patients compared to healthy controls and disease controls.
[0027] Figure 3 This represents the distribution of immunoglobulin subtypes with differentially expressed glycostructures in the BD group.
[0028] 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.
[0029] Figure 5 The ELISA small-sample verification was used to assess the binding strength of IgG4 protein to ECL in the plasma of BD patients. Detailed Implementation
[0030] The specific embodiments of this disclosure will be described in detail below with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are for illustration and explanation only and are not intended to limit this disclosure.
[0031] In this disclosure, the terms “Behçet’s disease,” “Behçet’s syndrome,” and “BD” are used interchangeably.
[0032] In this disclosure, the terms “Ketala lectin”, “ECL” and “ECA” are used interchangeably.
[0033] The first aspect of this disclosure provides a biomarker for screening or diagnosing Behcet's disease, said biomarker being an IgG4 protein with a glycosylated structure that specifically binds to Erythrina lectin.
[0034] In one embodiment of this disclosure, the glycosylated structure comprises Galβ4GlcNAc.
[0035] In this disclosure, the inventors have made a surprising discovery that the IgG4 protein specifically recognized and bound by Erythrina lectin, especially the glycosylated structure containing Galβ4GlcNAc, is significantly reduced in patients with Behcet's disease. Using the glycosylated IgG4 protein specifically bound by Erythrina lectin as a biomarker can provide a faster and more accurate clinical assessment of Behcet's disease or the risk of developing Behcet's disease, and provide strong technical support for the clinical treatment or prevention of Behcet's disease.
[0036] A second aspect of this disclosure provides a system for screening or diagnosing Behçet's disease, the system comprising:
[0037] The device includes an apparatus for detecting IgG4 protein glycosylation structure lectin signal values, a computing device, an input device for inputting standardized IgG4 protein glycosylation structure lectin signal values, and an output device for outputting a distinction between normal individuals and patients with Behçet's disease; wherein the computing 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 perform calculations for correcting and standardizing IgG4 protein glycosylation structure lectin signal values, as well as to distinguish Behçet's disease.
[0038] 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.
[0039] The standardization calculation is as follows: the IgG4 protein glycosylation structure lectin correction signal value is divided by the quantitative concentration value of IgG4 protein to obtain the IgG4 protein glycosylation structure lectin standardized signal value.
[0040] The Behçet's disease is determined as follows: if the ratio of the IgG4 protein glycosylation structure lectin standardized signal value of the patient to that of the healthy control is greater than the judgment threshold and has a statistically significant difference, then the patient is determined to have Behçet's disease or is at risk of having Behçet's disease.
[0041] In this disclosure, statistical difference refers to the result obtained through the Mann-Whitney test. P <0.05.
[0042] According to this disclosure, the judgment threshold is any value greater than 1.0, preferably any value in the range of 1.2-10.0, such as 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 any value between any two of them.
[0043] According to this disclosure, the device for detecting the IgG4 protein glycosylation structure lectin signal value includes an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled antibody against IgG4 protein, a lectin capable of specifically binding to the IgG4 protein glycosylation structure, and a chip signal reader.
[0044] The glycosylated structure comprises Galβ4GlcNAc; the lectin is Erythrina lectin.
[0045] This disclosure provides a third aspect of the use of materials from the system described in the second aspect for detecting IgG4 protein glycosylation structure lectin signal values in the preparation of a kit for screening or diagnosing Behcet's disease.
[0046] According to this disclosure, the material used to detect the IgG4 protein glycosylation structure lectin signal value is a material that can be detected from human blood samples.
[0047] In one embodiment of this disclosure, the kit contains an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled antibody against IgG4 protein, and a lectin capable of specifically binding to the IgG4 protein glycosylation structure.
[0048] In one embodiment of this disclosure, the lectin is Erythrina variegata lectin.
[0049] In one embodiment of this disclosure, the kit further comprises a fluorescent dye, a blocking agent, a diluent, and a washing solution;
[0050] The fluorescent dye is selected from at least one of Alexa Fluor® 647, Alexa Fluor® 488, Alex555 and Alex647;
[0051] The blocking agent is BSA (bovine serum albumin), preferably 1% BSA;
[0052] The diluent is BSA or PBST, preferably 1% BSA or 0.05% PBST; this diluent is used to dilute the sample.
[0053] The washing solution is PBST, preferably 0.05% PBST.
[0054] In one embodiment of this disclosure, the step of quantitatively detecting the IgG4 protein glycosylation structure lectin signal value includes:
[0055] S1. Obtain peripheral blood samples from patients with Behçet's disease;
[0056] S2. Determine the IgG4 protein glycosylation structure lectin signal value in the peripheral blood sample.
[0057] The present disclosure will be described in detail below through embodiments. It should be understood that the specific embodiments described herein are for illustration and explanation only and are not intended to limit the present disclosure.
[0058] Unless otherwise specified, all reagents, instruments, or equipment used in the following embodiments are commercially available.
[0059] Example 1
[0060] This example illustrates blood sample collection.
[0061] Patients with Behçet's syndrome (BD group): diagnosed according to the 2014 International Criteria for Behçet's Disease (ICBD) criteria or the 2009 International Study Group (ISG) criteria.
[0062] The disease control group (DC group) included: patients with Takayasu arteritis (TA) diagnosed according to the 1990 American College of Rheumatology diagnostic and classification criteria for Takayasu arteritis, designated as the TA group; all patients with ANCA-Associated Vasculitis (AAV) whose diagnoses met the 1993 Chapel Hill consensus on the diagnosis of ANCA-Associated Vasculitis, designated as the AAV group; and all patients with Primary Sjögren's Syndrome (pSS) meeting the American and European Consensus Criteria (AECG), designated as the pSS group.
[0063] Healthy control group (HC group): 30 healthy individuals who underwent physical examinations at the Peking Union Medical College Hospital's Physical Examination Center during the same period were included as healthy controls (HC). This group was defined as having normal imaging, laboratory, and internal and surgical examination results, and no history of autoimmune diseases, diabetes, cardiovascular diseases, tumors, or active infectious diseases.
[0064] Blood sample collection: Blood samples from all participants were first anticoagulated with EDTA and centrifuged at 12,000 rpm for 10 min. The supernatant plasma 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.
[0065] Table 1
[0066]
[0067] Example 2
[0068] This example illustrates the quantification of immunoglobulins.
[0069] 1. Immunoglobulin quantitative chip preparation: All blood samples, immunoglobulin standards and blank controls (with 1% BSA as the blank control) were printed on the surface of diluted glass slides by a spotting instrument. Each spot had two technical repeats.
[0070] 2. Blocking: Before the assay, the plasma chip was first blocked at room temperature with 1% BSA in a light-protected shaker at 12 rpm for 1 hour.
[0071] 3. Sample loading: The concentration of immunoglobulins in plasma is detected by incubating 100 μL / well (Table 2) of an appropriate fluorescently labeled detection antibody at room temperature and in the dark on a shaker at 12 rpm for 30 min.
[0072] Table 2. Detection antibodies for different immunoglobulin subtypes
[0073]
[0074] 4. Washing: Clean the chip three times with 0.05% PBST under light-protected conditions, and then wash twice with deionized water to remove unbound molecules.
[0075] 5. Chip Detection: After the chip is dried, the fluorescence signal is detected and analyzed using a GenePix 4300A microarray scanner (Molecular Devices, Sunnyvale, CA, USA) and GenePix Pro7 software (Molecular Devices, Sunnyvale, CA, USA).
[0076] 6. Quantification of immunoglobulins in plasma was performed using standard curves conforming to a 4- or 5-parameter logistic model, as described in the literature Yu, X., et al., Quantifying antibody binding on protein microarrays using microarray nonlinear calibration. Biotechniques, 2013. 54(5): p. 257-64., using the "nplr" package in R. The quantitative results are shown in Table 3.
[0077] Table 3
[0078]
[0079] Example 3
[0080] This embodiment is used to illustrate the detection of glycosylation structure of the proteome in blood samples.
[0081] 1. Preparations before the experiment:
[0082] (1) Preparation of laboratory-made lectin chip: The lectin chip was moved from -20℃ to 4℃ the night before the experiment. On the day of the experiment, the lectin chip was taken out 1 hour in advance and brought to room temperature for use.
[0083] (2) Reagent preparation: Prepare 1% BSA and 0.05% PBST respectively, filter them and temporarily store them at 4°C (they should also be stored at 4°C after use).
[0084] 2. Chip screening of samples:
[0085] (1) Sealing: Add a fence to the chip, add 100μL / well of 1% BSA to the chip, and seal at room temperature for 12rpm and 1h;
[0086] (2) Samples: Plasma was centrifuged at 12,000 rpm for 10 min at 4°C, and then diluted with 1% BSA at different ratios according to the different immunoglobulins being detected.
[0087] IgG and IgA antibody group: the volume ratio of serum to 1% BSA was 1:100;
[0088] IgG1+IgG3 antibody group: the volume ratio of serum to 1% BSA was 1:25;
[0089] IgG2 and IgG4 antibody groups: the volume ratio of serum to 1% BSA was 1:25;
[0090] Sample addition: Add diluted plasma sample to the agglutinin chip, 100 μL / well, and incubate on a shaker at room temperature for 12 rpm for 2 h;
[0091] (3) Washing: Wash three times with 0.05% PBST, 10 min each time;
[0092] (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 then dilute with 1% BSA. IgG+IgA, IgG1+IgG3, IgG2+IgG4, and IgA1+IgA2 can be detected in groups. Incubate 100 μL / well on a shaker at room temperature in the dark for 12 rpm for 1 h. For information on anti-immunoglobulin secondary antibodies, please refer to Table 2 above.
[0093] (5) Washing in the dark: Wash 3 times with 0.05% PBST for 10 min each time; then wash 2 times with sterile double-distilled water each time.
[0094] (6) Chip detection: After the chips were dried, 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). The scanning channels were as follows: IgG: 532; IgA, IgG3, IgG4, IgA1: 635; IgG1, IgG2, IgA2: 488.
[0095] 3. Data processing:
[0096] Chip data processing: The average F median signal value of two technically duplicated points of the same lectin on the chip is taken as the signal intensity of that lectin detection point. Samples with missing lectin detection signal points for a specific immunoglobulin subtype are removed. After removing duplicate samples, valid samples are obtained. Each lectin signal value on the chip is divided by 25% of the signal value of all buffers on the block containing that detection point for background correction. Because the expression levels of different immunoglobulin subtypes vary among different samples, each corrected signal value is standardized by dividing by the quantitative concentration value of the corresponding immunoglobulin subtype in that patient, thereby eliminating differential changes in glycosylation signals caused by excessively high or low plasma immunoglobulin concentrations in the study subjects.
[0097] Statistical analysis and determination of BD-related 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, healthy control group, and disease control group were identified using the Man-Whitney test. The fold change of the lectin detection signal value of each immunoglobulin in the BD group compared to the healthy control group and the disease control group was calculated. fold changes greater than 1 between any two groups were identified as BD-related indicators; indicators with fold changes greater than 1.2 and p < 0.05 will undergo further methodological validation in subsequent ELISA experiments.
[0098] 4. Experimental Results:
[0099] The significant changes in glycosylation signal values in the BD group compared to healthy controls and disease controls are shown in the following figure. Figure 1 The glycostructures showing up- or down-regulated expression of plasma immunoglobulins in the BD group compared to the healthy control group and disease control group are shown in the figure. Figure 2 ,according to Figure 2 The Venn diagram shows that the glycan levels of plasma immunoglobulins bound to chip lectins are significantly correlated with BD.
[0100] like Figure 3As shown, in terms of immunoglobulin subtypes, changes in IgG glycans were the most common, accounting for 87.9% (29 / 33) of all changes. In addition, IgA and IgG1 glycans also changed: IgA was black elderberry lectin (SNA) bound to sialic acid, and IgG1 was banana lectin (BanLec) bound to sialic acid and vitex lectin (UEA-I) bound to fucose.
[0101] like Figure 4 As shown, the IgG4 protein containing the Galβ4GlcNAc glycosylation structure recognized by Erythrina lectin (ECL) was significantly reduced in BD. Compared with the control group, the fold change in expression levels of 13 IgG glycans and 1 IgA glycan in BD was greater than 1.2, and the fold change in expression level of IgG4 glycoprotein in BD was 0.3 (equivalent to the leukin-normalized signal value of IgG4 protein glycosylation structure in BD patients / the leukin-normalized signal value of IgG4 protein glycosylation structure in HC group = 1 / 0.3 = 3.3) and 0.84 (equivalent to the leukin-normalized signal value of IgG4 protein glycosylation structure in BD patients / the leukin-normalized signal value of IgG4 protein glycosylation structure in DC patients = 1 / 0.84 = 1.19) compared with the disease control group.
[0102] Example 5
[0103] ECL / ECA-specific IgG4 protein is downregulated in BD, with significant fold-fold changes. Extensive evidence suggests that complement plays a central role in the pathogenesis of BD, and that non- / low-galactosylated IgG has pro-inflammatory and cell-damaging effects, correlated with the development of immune diseases such as rheumatoid arthritis and membranous nephropathy. Hypothesizing that low-galactosylated IgG4 may participate in complement activation via the lectin pathway, thereby contributing to the development of BD, we used ELISA to incubate ECL-coated plasma. After incubation with HRP-labeled mouse anti-human IgG4 Fc secondary antibody and subsequent TMB staining, we found a significant increase in the binding strength of ECL in the plasma of BD patients. Figure 5 Based on literature reports, this may indicate that the presence of components such as agalactosylated / low-galactosylated immunoglobulins in the patient's plasma can easily activate complement and promote inflammatory responses.
[0104] The preferred embodiments of this disclosure have been described in detail above with reference to the accompanying drawings. However, this disclosure is not limited to the specific details of the above embodiments. Within the scope of the technical concept of this disclosure, various simple modifications can be made to the technical solutions of this disclosure, and these simple modifications all fall within the protection scope of this disclosure.
[0105] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, this disclosure will not describe the various possible combinations separately.
[0106] Furthermore, various different embodiments of this disclosure can be combined in any way, as long as they do not violate the spirit of this disclosure, they should also be regarded as the content disclosed in this disclosure.
Claims
1. A system for screening or diagnosing Behçet's disease, characterized in that, The system includes: The device includes an apparatus for detecting the signal value of IgG4 protein glycosylation structure lectin, a computing device, an input device for inputting the standardized signal value of IgG4 protein glycosylation structure lectin, and an output device for outputting the distinction between normal individuals and patients with Behçet's disease; wherein the computing 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 perform correction calculation and standardization calculation of the IgG4 protein glycosylation structure lectin signal value, as well as the distinction 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 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: the IgG4 protein glycosylation structure lectin correction signal value is divided by the quantitative concentration value of IgG4 protein to obtain the IgG4 protein glycosylation structure lectin standardized signal value. The Behçet's disease is determined as follows: if the ratio of the IgG4 protein glycosylation structure lectin standardized signal value of the patient to the IgG4 protein glycosylation structure lectin standardized signal value of the healthy control is greater than the judgment threshold and has a statistical difference, then the patient is determined to have Behçet's disease or has the risk of having Behçet's disease. The glycosylated structure comprises Galβ4GlcNAc; the lectin is Erythrina lectin.
2. The system according to claim 1, wherein, The threshold value is any value greater than 1.
0.
3. The system according to claim 2, wherein, The judgment threshold is any value within the range of 1.2-10.
0.
4. The system according to claim 1, wherein, The device for detecting the IgG4 protein glycosylation structure lectin signal value includes an IgG4 protein glycosylation structure lectin signal value detection chip, a fluorescently labeled antibody against IgG4 protein, a lectin that can specifically bind to the IgG4 protein glycosylation structure, and a chip signal reader.
5. Use of the material used in the system of claim 1 to detect the IgG4 protein glycosylation structure lectin signal value in the preparation of a kit for screening or diagnosing Behcet's disease.
6. The use according to claim 5, wherein, The material used to detect the IgG4 protein glycosylation structure lectin signal value is a material that can be detected from human blood samples.
7. The use according to claim 5, 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 lectin.
8. The use according to claim 7, 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 sealing agent is BSA; The diluent is BSA or PBST; The washing solution is PBST.
9. The use according to claim 7, 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.