Protein antigen combination for aortic dissection detection and use thereof

Abstract

The present invention belongs to the field of biological detection, and specifically relates to a protein antigen combination for aortic dissection detection and the use thereof. The specific technical solution comprises an antigen composition comprising an FBN2 protein fragment and an SPEG protein, wherein the FBN2 protein fragment has an amino acid sequence as shown in SEQ ID NO: 1, and the SPEG protein has an amino acid sequence as shown in SEQ ID NO: 5. Provided are a protein antigen and a specific combination of antigens, which, by means of detecting autoantibodies corresponding thereto, can be used for the detection or diagnosis of aortic dissection, are particularly suitable for risk assessment and prediction prior to the onset of aortic dissection, and can be further prepared into a related reagent or kit on the basis of requirements.

Description

A protein antigen combination for aortic dissection detection and application TECHNICAL FIELD

[0001] The present application belongs to the field of biological detection, and particularly relates to a protein antigen combination for aortic dissection detection and application. BACKGROUND

[0002] The aorta is composed of three layers: intima, media and adventitia. The intima is in direct contact with the blood in the blood vessel and is mainly composed of a layer of endothelial cells on the basement membrane. Aortic dissection is an acute condition characterized by separation between the intima and the media of the aortic wall, followed by the formation of a false lumen. On the one hand, the false lumen can compress the true aortic lumen, causing poor blood flow or even occlusion of the blood vessel; on the other hand, blood in the false lumen is easily thrombosed; at the same time, aortic dissection is prone to cause arterial rupture, which poses a life-threatening risk to patients.

[0003] Aortic dissection is generally caused by a tear in the aortic intima. The high pressure in the aorta causes the blood in the artery to enter the media from the intima tear, causing the media to separate and expand along the long axis of the aorta, forming a true and false lumen separation state of the aortic wall. In addition, about 13% of aortic dissection patients do not find intimal tears, and the cause may be intramural hematoma (caused by intramural hemorrhage). Aortic dissection caused by intramural hematoma does not have a direct connection between the true and false lumens, so it is difficult to accurately diagnose by aortic angiography.

[0004] Aortic dissection develops rapidly, and the early mortality rate is very high, so many patients have died before diagnosis, making it difficult to determine the overall incidence. Untreated, aortic dissection is a fatal disease, with an estimated mortality rate of 40% at the first onset; if not treated in time, the mortality rate increases by 1% per hour within 48 hours of onset, and the annual mortality rate can be more than 90%. Therefore, rapid and accurate diagnosis of aortic dissection has important clinical value.

[0005] Currently, clinical diagnosis of aortic dissection mainly relies on clinical symptoms combined with imaging methods. According to the guidelines for diagnosis and treatment of aortic dissection, sudden onset of severe chest pain and / or back pain is the most typical manifestation of aortic dissection. The guidelines recommend that patients with acute chest pain be considered as suspected cases of aortic dissection, and further laboratory and imaging examinations be performed.

[0006] The imaging examination of aortic dissection is mainly CT angiography (CTA) and magnetic resonance imaging (MRI). CTA belongs to interventional examination, which needs to inject iodine contrast agent, and is difficult to be used for patients with iodine allergy, impaired renal function, pregnancy, hyperthyroidism and the like. MRI scanning time is relatively long, and the cooperation degree of patients with unstable circulation is low, and it is contraindicated for patients with in-vivo implanted life-assisting devices and metal objects. Therefore, the application of imaging examination is limited.

[0007] Aortic dissection can also be diagnosed by detecting biomarkers in blood. The guideline recommends detecting D-dimer as a biomarker. When D-dimer in blood increases, especially rapidly in a short time, the possibility of diagnosing aortic dissection increases, but differential diagnosis with pulmonary embolism is still needed, and D-dimer can be used as an exclusion index for the diagnosis of acute aortic dissection.

[0008] Autoantibody is an antibody produced by the immune system of an individual against the protein antigen of the individual itself. Normally, the immune system produces antibodies in response to exogenous proteins or substances in the body, and does not produce antibodies to the cells and components of the body itself. However, in some special cases, especially in pathological conditions, the immune system also recognizes one or more endogenous components of the body, resulting in the production of autoantibodies.

[0009] Autoantibody detection has been widely used in clinical diagnosis, such as anti-thyroid autoantibody detection, anti-nuclear antibody detection, and anti-phospholipid antibody detection. Disease-associated autoantibody (AAB) is an important biomarker, which can be used not only for the diagnosis of a specific disease, but also for the diagnosis of the early stage (single or few symptoms) of the disease or the diagnosis of the disease without typical clinical manifestations (atypical form), and even for the early warning years before the onset of the disease.

[0010] Currently, there is no specific biomarker for aortic dissection in clinical practice. Therefore, if a specific biomarker with accurate detection and high detection effect can be developed, it will have a wide clinical application prospect.

[0011] SUMMARY

[0012] The purpose of the present application is to provide a protein antigen combination for aortic dissection detection and application.

[0013] To achieve the above-mentioned purpose of the application, the technical scheme adopted by the present application is that an antigen, the antigen is a fragment of FBN2 protein, and the amino acid sequence is shown as SEQ ID NO: 1.

[0014] Correspondingly, an antigen combination comprising the antigen, the antigen combination further comprises SPEG protein, and the amino acid sequence of the SPEG protein is shown as SEQ ID NO: 5.

[0015] Preferably, the antigen combination further includes a fragment of SGCD protein, the amino acid sequence of which is shown in SEQ ID NO: 10.

[0016] Preferably, the antigen combination further includes a fragment of SMTN protein, the amino acid sequence of which is shown in SEQ ID NO: 4; or; the antigen combination further includes a fragment of COL3A1 protein, the amino acid sequence of which is shown in SEQ ID NO: 8.

[0017] Preferably, the antigen combination further includes a fragment of SMTN protein and a fragment of COL3A1 protein, the amino acid sequence of the SMTN protein fragment being shown in SEQ ID NO: 4, and the amino acid sequence of the COL3A1 protein fragment being shown in SEQ ID NO: 8.

[0018] Preferably, the antigen combination further includes a fragment of MAT2A protein and a fragment of CNN2 protein, the amino acid sequence of the MAT2A protein fragment being shown in SEQ ID NO: 3, and the amino acid sequence of the CNN2 protein fragment being shown in SEQ ID NO: 9.

[0019] Preferably, the antigen combination further includes fragments of COL3A1 protein, MAT2A protein, and CNN2 protein, wherein the amino acid sequence of the COL3A1 protein fragment is shown in SEQ ID NO: 8, the amino acid sequence of the MAT2A protein fragment is shown in SEQ ID NO: 3, and the amino acid sequence of the CNN2 protein fragment is shown in SEQ ID NO: 9.

[0020] or;

[0021] The antigen combination also includes fragments of EFEMP2 protein, COL3A1 protein, MAT2A protein, and CNN2 protein. The amino acid sequence of the EFEMP2 protein fragment is shown in SEQ ID NO: 7, the amino acid sequence of the COL3A1 protein fragment is shown in SEQ ID NO: 8, the amino acid sequence of the MAT2A protein fragment is shown in SEQ ID NO: 3, and the amino acid sequence of the CNN2 protein fragment is shown in SEQ ID NO: 9.

[0022] or;

[0023] The antigen combination further comprises a fragment of FBN1 protein, a fragment of ACTA2 protein, a fragment of COL3A1 protein, a fragment of MAT2A protein and a fragment of CNN2 protein, the amino acid sequence of the fragment of FBN1 protein is shown as SEQ ID NO: 6, the amino acid sequence of the fragment of ACTA2 protein is shown as SEQ ID NO: 2, the amino acid sequence of the fragment of COL3A1 protein is shown as SEQ ID NO: 8, the amino acid sequence of the fragment of MAT2A protein is shown as SEQ ID NO: 3, and the amino acid sequence of the fragment of CNN2 protein is shown as SEQ ID NO: 9.

[0024] Correspondingly, an antigen combination comprises a fragment of ACTA2 protein, a fragment of COL3A1 protein, a fragment of CNN2 protein, a fragment of SMTN protein and a fragment of ROBO4 protein, the amino acid sequence of the fragment of ACTA2 protein is shown as SEQ ID NO: 2, the amino acid sequence of the fragment of COL3A1 protein is shown as SEQ ID NO: 8, the amino acid sequence of the fragment of CNN2 protein is shown as SEQ ID NO: 9, the amino acid sequence of the fragment of SMTN protein is shown as SEQ ID NO: 4, and the amino acid sequence of the fragment of ROBO4 protein is shown as SEQ ID NO: 11.

[0025] Correspondingly, an antigen is SPEG protein, and the amino acid sequence is shown as SEQ ID NO: 5; or the antigen is a fragment of EFEMP2 protein, and the amino acid sequence is shown as SEQ ID NO: 7.

[0026] Correspondingly, a product for detecting / identifying aortic dissection, arterial tear and arterial injury is prepared by using the antigen and / or the antigen combination.

[0027] The present application has the following beneficial effects:

[0028] The present application provides specific protein markers related to aortic dissection, arterial tear and arterial injury. By detecting the presence of autoantibodies corresponding to these protein markers in the human body, the risk of aortic dissection of the detected person can be effectively evaluated. The protein markers provided by the present application, especially the protein marker combination, not only ensure high specificity of detection, but also greatly improve the sensitivity of detection, which has extremely important practical significance in clinical application.

[0029] The biological sample for detection can be serum, plasma, whole blood, saliva, oral mucosa swab, urine, lymph, cerebrospinal fluid, etc. According to specific conditions, the biological sample can be pretreated by extraction, dilution, enrichment, etc. The method is various, simple and easy to operate.

[0030] The antigen or antigen combination provided by the application can also be used for preparing an aortic dissection, an arterial tear, an arterial injury related autoantibody detection reagent or an aortic dissection diagnosis reagent. It should be understood that the protein antigen combination can also be used for preparing an aortic dissection related autoantibody detection kit, which can be prepared according to the method and reagent used for detecting the aortic dissection related autoantibody in the examples of the application, and can also be adjusted accordingly according to the need.

[0031] In summary, the application provides a protein antigen and a specific antigen combination, which can be used for detecting or assisting in diagnosing an aortic dissection, an arterial tear and an arterial injury, and is also suitable for risk assessment and prediction of aortic dissection; and can be further prepared into a related reagent or kit according to the need. DETAILED DESCRIPTION

[0032] The application finds that the proteins FBN2, ACTA2, MAT2A, SMTN, SPEG, FBN1, EFEMP2, COL3A1, CNN2, SGCD and ROBO4 are closely related to the diagnosis of aortic dissection.

[0033] The application further discloses that specific protein fragments or whole proteins of the above proteins have prominent advantages in aortic dissection diagnosis. The specific protein fragments include FBN2 (29-50), ACTA2 (30-120), MAT2A (238-290), SMTN (106-310), SPEG (1-113, whole protein), FBN1 (2235-2294), EFEMP2 (24-51), COL3A1 (90-152), CNN2 (148-309), SGCD (1-35) and ROBO4 (451-733). The FBN2 protein fragment sequence is shown as SEQ ID NO: 1. The ACTA2 protein fragment sequence is shown as SEQ ID NO: 2. The MAT2A protein fragment sequence is shown as SEQ ID NO: 3. The SMTN protein fragment sequence is shown as SEQ ID NO: 4. The SPEG protein sequence is shown as SEQ ID NO: 5. The FBN1 protein fragment sequence is shown as SEQ ID NO: 6. The EFEMP2 protein fragment sequence is shown as SEQ ID NO: 7. The COL3A1 protein fragment sequence is shown as SEQ ID NO: 8. The CNN2 protein fragment sequence is shown as SEQ ID NO: 9. The SGCD protein fragment sequence is shown as SEQ ID NO: 10. The ROBO4 protein fragment sequence is shown as SEQ ID NO: 11.

[0034] Based on the new discovery, the application provides application of the above proteins in preparation of products (for example, kits) for detecting and diagnosing aortic dissection. The above proteins and protein fragments can be used alone or in combination to form a protein (fragment) composition.

[0035] The technical solutions in the embodiments of the application will be clearly and completely described below. Obviously, the described embodiments are only some of the embodiments of the application, but not all the embodiments. If not specifically indicated, the technical means used in the embodiments are conventional means familiar to those skilled in the art. The obtained data are all average values obtained after at least three repetitions, and the data obtained in each repetition are all effective data.

[0036] Embodiment one: construction, expression, purification and performance display of protein antigens

[0037] 1. Construction and expression of antigen recombinant vectors. The protein antigens in Table 1 are selected by analyzing their sequences, structures, functions and expression distribution.

[0038] Table 1: Database ID correspondence table of protein antigens

[0039] The human cDNA library (purchased from Invitrogen Corporation) or full gene synthetic DNA is used as a template to design primers, and the genes of the proteins are cloned into pET28 plasmid by means of PCR, enzyme digestion, ligation and other molecular cloning methods. Meanwhile, HIS, c-myc and other tags are added to the N-terminus of the proteins to form fusion proteins. The obtained recombinant expression vectors are identified by DNA sequencing to confirm that they contain correct protein genes. It should be noted that the added tags are only for the convenience of identification and extraction of the proteins, and do not have a decisive influence on the functions of the proteins as antigens. When used, no tag or other tags can be added as needed.

[0040] The recombinant plasmid containing the protein gene is transformed into E. coli BL21 (DE3) competent cells, and the clones are inoculated into LB medium and cultured at 37°C on a shaker. When the bacterial density reaches OD 600 about 0.8, the temperature is lowered to 16°C, 0.1 mM isopropyl thiogalactoside (IPTG) is added to each LB medium, and expression is induced overnight to obtain the bacterial cells.

[0041] 2. Purification of antigens. The induced expression bacterial cells are collected by centrifugation and rinsed twice with PBS. The bacterial cells are resuspended and dispersed with lysis buffer (5-10 mL of lysis buffer per g of bacterial cells), ice-bathed, and the bacterial cells are broken by ultrasonic waves (ultrasonic power 200 W, breaking for 5 s and resting for 5 s). After breaking, the bacterial cells are centrifuged at 13,000 rpm and 10°C for 20 min, and the supernatant is purified by Ni column affinity chromatography and molecular sieve chromatography. After SDS-PAGE electrophoresis analysis, the molecular weight and purity of the protein are confirmed, the concentration is determined by the Bradford method, and the protein is stored at -80°C for later use. The purified protein to be tested is obtained, and the yield is calculated (the yield results are shown in Table 2).

[0042] 3. ELISA detection of the performance of the protein (fragment) antigen.

[0043] The solutions and reagents used for detection are as follows:

[0044] The coating buffer is PBS buffer with pH = 7.4. The preparation method is as follows: accurately weigh 3.58 g of Na2HPO4·12H2O, 0.23 g of KH2PO4·2H2O, 0.2 g of KCl and 8.0 g of NaCl, dissolve them in water, and add water to make up to 1 L.

[0045] Blocking solution / sample diluent / antibody diluent: 10 g of BSA (bovine serum albumin) is dissolved in the coating buffer, and water is added to make up to 1 L.

[0046] Washing solution: freshly prepared. Before use, 0.05% Tween 20 (V / V) is added to the coating buffer with pH = 7.4.

[0047] TMB color developing reagent, purchased from KPL.

[0048] Termination solution: 1M hydrochloric acid.

[0049] (1) Solid phase coating of the protein to be tested. The purified antigen to be tested obtained in step 2 was diluted to 5 μg / mL with coating buffer, and added to a 96-well plate at 50 μL per well, and coated at 4°C overnight. The next day, the solution was discarded, and the plate was spun dry, and washed three times with washing buffer at 200 μL per well each time. Then 200 μL of blocking solution was added to each well, and incubated at room temperature for 1 h. After the blocking solution was discarded and the plate was spun dry, it was washed three times with washing buffer at 200 μL per well each time, and spun dry again. The solid phase coated antigen was obtained in the 96-well plate.

[0050] (2) Addition of the sample to be tested. The human serum to be tested was diluted 100-fold with sample diluent, and added to the 96-well plate containing the protein to be tested at 50 μL per well. The 96-well plate was then placed in a microplate shaker, and incubated at room temperature for 1 h with shaking. The plate was spun dry, and washed three times with washing buffer at 200 μL per well each time, and spun dry again.

[0051] (3) Addition of enzyme-labeled secondary antibody. 1.0 mg / mL horseradish peroxidase-labeled recombinant sheep anti-human immunoglobulin G antibody (purchased from Jackson ImmunoResearch Inc.) was diluted 20,000-fold with antibody diluent, and added to the 96-well plate treated in step 3 at 50 μL per well. The 96-well plate was then placed in a microplate shaker, and incubated at room temperature for 0.5 h with shaking. The plate was spun dry, and washed three times with washing buffer at 200 μL per well each time, and spun dry again.

[0052] (4) Color development reaction and reading of optical density values. To the 96-well plate treated in step (3), 50 μL of TMB color developing reagent was added per well, and shaken for 15 s. The reaction was carried out at room temperature for 15 min in the dark, and 50 μL of termination solution was added. Then the absorbance value at 450 nm was read using an enzyme-labeled instrument, and the detection signal (S) of each sample to be tested was obtained.

[0053] (5) Sensitivity and specificity analysis. Respectively take 48 cases of positive samples (serum of patients diagnosed with aortic dissection) and 46 cases of negative samples (serum of healthy subjects), according to the above method (absorbance value of 450 nm wavelength), determine the detection signal (S) of each sample. It should be noted that: in the present application, the detection is to detect the corresponding autoantibody of the antigen or antigen combination, which will not be described below. Take the negative sample as the negative reference sample, calculate the average (M) and standard deviation (SD) of the detection signal (S) of all negative reference samples, and take M+2SD as the Cut Off value. The sample with detection signal (S) ≥Cut Off value (S≥M+2SD) is defined as positive; the sample with detection signal (S) <Cut Off value (S

[0054] The specificity and sensitivity are calculated based on the positive and negative results of the samples. Among them, the specificity refers to the proportion of healthy subject samples that are correctly determined as negative, that is, the number of samples that are correctly determined as negative in the negative samples divided by the total number of negative samples. The sensitivity refers to the proportion of aortic dissection patient samples that are correctly determined as positive, that is, the number of samples that are determined as positive in the positive samples divided by the total number of positive samples. The sensitivity and specificity of each measured antigen alone in sample detection are calculated. The results are shown in Table 2. Among them, the full protein of FBN2, FBN1, COL3A1 and ROBO4 protein is not obtained.

[0055] Table 2 Sensitivity and specificity display table of each protein antigen

[0056] Example Two: Selection and performance display of protein fragments

[0057] Referring to the method of Example One, the sequences, structures, functions and expression distribution of the proteins in Table 1 are analyzed, and different fragments are selected for cloning, respectively. The protein SPEG is not cloned fragment, and the full protein is used. The specific selected protein fragments are shown in Table 3.

[0058] Table 3 Cloning sequence corresponding table of protein antigen fragments

[0059] Referring to the method of Example One, the yield of each fragment is calculated. Using the same samples as in Example One, the sensitivity and specificity of each antigen in Table 3 alone in sample detection are detected and calculated. The results are shown in Table 4.

[0060] Table 4 Sensitivity and specificity display table of each antigen

[0061] According to the results of Table 4, one optimal fragment was selected from each of the protein antigens, and the results are shown in Table 5. The preferred protein antigen fragments not only have good specificity and sensitivity, but also have high yield, which is conducive to subsequent scale-up and production.

[0062] Table 5: Sensitivity and specificity of preferred antigen fragments

[0063] Example Three: Detection effect of antigen combination

[0064] Different antigen combinations were formed by selecting different antigen fragments from Table 5 of Example Two, and the antigen combinations are shown in Table 6. It should be noted that the inventors did not only conduct the combination tests of Table 6; the inventors obtained the antigen combinations shown in Table 6 after a large number of preliminary tests, and only selected some combinations with better effects due to the limited space.

[0065] Table 6: Comparison table of each antigen combination

[0066] 2. 48 positive samples (aortic dissection patients) and 46 negative samples (healthy subjects) were taken, and the sensitivity and specificity of each sample were detected using the detection method of Example One and each antigen combination in Table 6.

[0067] The definition method of positive and negative of a single antigen in an antigen combination refers to Example One. The overall sensitivity and specificity of the antigen combination are defined as follows:

[0068] For an antigen combination, when the detection signal of a serum sample using any one antigen in the combination is a positive detection signal, the serum sample is a positive sample; otherwise, the serum sample is a negative sample.

[0069] Based on the above positive and negative definition method, the positive and negative results of an antigen combination are obtained by detection, and the sensitivity of the antigen combination in patient samples is calculated.

[0070] Among them, the sensitivity refers to the proportion of aortic dissection patient samples that are correctly determined as positive, that is, the number of aortic dissection patient samples determined as positive divided by the total number of aortic dissection patient samples; the specificity refers to the proportion of healthy subject samples that are correctly determined as negative, that is, the number of healthy subject samples determined as negative divided by the total number of healthy subject samples.

[0071] The sensitivity and specificity results of each group of antigen combinations obtained by detection are shown in Table 7.

[0072] Table 7: Sensitivity and specificity detection results of each group of antigen combinations

[0073] In the later application, one or more of the ideal candidate antigens provided by the present application can be selected as needed to make a diagnostic kit.

[0074] The above-described embodiments are merely preferred modes of the present application, and are not intended to limit the scope of the present application. Various modifications, variations, changes, substitutions, and the like made by those skilled in the art to the technical solutions of the present application without departing from the design spirit of the present application shall fall within the protection scope of the present application as defined by the claims.

Claims

1. An antigen, characterized in that: The antigen is a fragment of FBN2 protein, and the amino acid sequence is shown as SEQ ID NO:

1.

2. An antigen combination, characterized by: The antigen of claim 1 further comprises SPEG protein, and the amino acid sequence of the SPEG protein is shown as SEQ ID NO:

5.

3. The antigen combination according to claim 2, characterized in that: The antigen combination further comprises a fragment of SGCD protein, and the amino acid sequence of the fragment of SGCD protein is shown as SEQ ID NO:

10.

4. The antigenic combination according to claim 3, characterized in that: The antigen combination further comprises a fragment of SMTN protein, and the amino acid sequence of the fragment of SMTN protein is shown as SEQ ID NO: 4; or; the antigen combination further comprises a fragment of COL3A1 protein, and the amino acid sequence of the fragment of COL3A1 protein is shown as SEQ ID NO:

8.

5. The antigenic combination according to claim 3, characterized in that: The antigen combination further comprises a fragment of SMTN protein and a fragment of COL3A1 protein, and the amino acid sequence of the fragment of SMTN protein is shown as SEQ ID NO: 4, and the amino acid sequence of the fragment of COL3A1 protein is shown as SEQ ID NO:

8.

6. The antigenic combination according to claim 5, characterized in that: The antigen combination further comprises a fragment of MAT2A protein and a fragment of CNN2 protein, and the amino acid sequence of the fragment of MAT2A protein is shown as SEQ ID NO: 3, and the amino acid sequence of the fragment of CNN2 protein is shown as SEQ ID NO:

9.

7. The antigen combination of claim 2, wherein: The antigen combination further comprises a fragment of COL3A1 protein, a fragment of MAT2A protein and a fragment of CNN2 protein, and the amino acid sequence of the fragment of COL3A1 protein is shown as SEQ ID NO: 8, the amino acid sequence of the fragment of MAT2A protein is shown as SEQ ID NO: 3, and the amino acid sequence of the fragment of CNN2 protein is shown as SEQ ID NO: 9; Or; The antigen combination further comprises a fragment of EFEMP2 protein, a fragment of COL3A1 protein, a fragment of MAT2A protein and a fragment of CNN2 protein, and the amino acid sequence of the fragment of EFEMP2 protein is shown as SEQ ID NO: 7, the amino acid sequence of the fragment of COL3A1 protein is shown as SEQ ID NO: 8, the amino acid sequence of the fragment of MAT2A protein is shown as SEQ ID NO: 3, and the amino acid sequence of the fragment of CNN2 protein is shown as SEQ ID NO: 9; Or; ​ The antigen combination further comprises a fragment of FBN1 protein, a fragment of ACTA2 protein, a fragment of COL3A1 protein, a fragment of MAT2A protein and a fragment of CNN2 protein, the amino acid sequence of the fragment of FBN1 protein is shown as SEQ ID NO: 6, the amino acid sequence of the fragment of ACTA2 protein is shown as SEQ ID NO: 2, the amino acid sequence of the fragment of COL3A1 protein is shown as SEQ ID NO: 8, the amino acid sequence of the fragment of MAT2A protein is shown as SEQ ID NO: 3, and the amino acid sequence of the fragment of CNN2 protein is shown as SEQ ID NO:

9.

8. An antigen combination, characterized by: The antigen combination comprises a fragment of ACTA2 protein, a fragment of COL3A1 protein, a fragment of CNN2 protein, a fragment of SMTN protein and a fragment of ROBO4 protein; the amino acid sequence of the fragment of ACTA2 protein is shown as SEQ ID NO: 2, the amino acid sequence of the fragment of COL3A1 protein is shown as SEQ ID NO: 8, the amino acid sequence of the fragment of CNN2 protein is shown as SEQ ID NO: 9, the amino acid sequence of the fragment of SMTN protein is shown as SEQ ID NO: 4, and the amino acid sequence of the fragment of ROBO4 protein is shown as SEQ ID NO:

11.

9. An antigen for detecting / identifying aortic dissection, arterial tear, arterial injury, characterized by: The antigen is a fragment of EFEMP2 protein, and the amino acid sequence is shown as SEQ ID NO:

7.

10. A product for detecting / identifying aortic dissection, arterial tear and arterial injury, which is prepared by using the antigen of claim 1 or 9 and / or the antigen combination of any one of claims 2-8 or the SPEG protein, and the amino acid sequence of the SPEG protein is shown as SEQ ID NO: 5.

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