Application of CD62P and / or platelet-neutrophil aggregate as auxiliary diagnosis marker for myasthenia gravis

Abstract

The invention discloses application of CD62P and / or platelet-neutrophil aggregate as a myasthenia gravis auxiliary diagnosis marker, and belongs to the technical field of disease auxiliary diagnosis markers. The invention provides an application of CD62P and / or platelet-neutrophil aggregate as a myasthenia gravis auxiliary diagnosis marker, and further provides an application of the CD62P and / or platelet-neutrophil aggregate in preparation of a myasthenia gravis auxiliary diagnosis reagent. Based on the application, a related auxiliary diagnosis reagent for myasthenia gravis and an auxiliary diagnosis system for myasthenia gravis are provided. The auxiliary diagnosis marker and the auxiliary diagnosis system method provided by the invention can provide important reference basis for early auxiliary diagnosis and disease monitoring of MG, and improve the accuracy and efficiency of clinical auxiliary diagnosis.

Description

Technical Field

[0001] The present invention belongs to the technical field of disease auxiliary diagnosis markers, and in particular relates to the use of CD62P and / or platelet-neutrophil aggregates as auxiliary diagnosis markers for myasthenia gravis. Background Art

[0002] Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies attack the neuromuscular junction, manifesting as fluctuating skeletal muscle weakness and fatigue. In severe cases, respiratory muscles are affected and even life-threatening, causing some young and middle-aged patients to lose their ability to work. With the aging of the population and the improvement of diagnosis and treatment technology, the incidence of MG has gradually increased worldwide in the past 70 years. A 2020 survey of inpatients in 1,665 tertiary hospitals across the country showed that the incidence of MG in my country was about 0.68 / 100,000. Since the survey did not include outpatients, the actual incidence may be much higher than this. The 2022 Red Book of China's MG Patient Health Report shows that the incidence of MG in the young population in my country is high, and multiple factors can lead to repeated illness, which has brought a heavy economic burden to society and patients. However, the initiation link of the pathogenesis of MG patients is not fully understood. It is currently believed that it may be related to the activation of innate immunity in the thymus to form a chronic inflammatory environment. The chronic inflammatory environment is considered to be an important initiating factor of Th cell imbalance and Treg dysfunction. At the same time, the imbalance and dysfunction of Th1 / Th2 and Th17 / Treg ratios maintain the chronic inflammatory environment in the thymus, promoting the autosensitization and production of pathogenic antibodies AChR. In recent years, research on platelets in innate immunity has continued to emerge, and they have gradually been regarded as an important part of the immune system.

[0003] CD62P, also known as P-selectin or GMP 140, is a member of the selectin family of adhesion molecules, a cell surface glycoprotein. Activated platelets relocate P-selectin, which is initially present in cytoplasmic granules, to their surface and can therefore be used to characterize activated platelets (CD62P-positive platelets). The platelet satellite phenomenon around neutrophils, namely platelet-neutrophilaggregates (PNAs), is a characteristic of selective platelet adhesion to neutrophils in whole blood.

[0004] The clinical manifestations of MG are extremely heterogeneous, and skeletal muscles throughout the body can be affected, showing fluctuating weakness and easy fatigability. The symptoms are "lighter in the morning and heavier in the evening", aggravated after activity and relieved after rest. On the basis of typical MG clinical features (fluctuating muscle weakness), pharmacological examinations (neostigmine test is positive), electrophysiological examinations (repeated nerve electrical stimulation and single fiber electromyography) and serum anti-AChR and other antibody tests (AChR antibodies can be detected in about 50%~60% of OMG and 85%~90% of GMG serum, MuSK antibodies can be detected in 10%~20% of AChR antibody-negative MG patients; LRP4 antibodies can be detected in 7%~33% of AChR and MuSK antibody-negative MG patients) can be used for auxiliary diagnosis if one abnormality is met, and other diseases need to be excluded. All confirmed MG patients need to further complete thymic imaging examinations (mediastinal CT or MRI) and further subgroup classification.

[0005] However, the incidence of MG is low, and nearly 80% of patients present with simple ocular muscle symptoms, which can easily lead to missed or misdiagnosis in the early stages. For some patients with atypical clinical manifestations and no significant abnormalities in antibody and electrophysiological test results, auxiliary diagnosis is often difficult.

[0006] There is no report in the prior art of this field on the use of CD62P or PNAs to assist in the diagnosis of myasthenia gravis. Summary of the invention

[0007] In order to fill the above technical gaps in the prior art and develop the auxiliary diagnosis use of CD62P or PNAs, the present invention provides the use of CD62P and / or PNAs as auxiliary diagnosis markers for myasthenia gravis.

[0008] The technical solution of the present invention is as follows: Use of CD62P and / or platelet-neutrophil aggregates as auxiliary diagnostic markers for myasthenia gravis.

[0009] Use of CD62P and / or platelet-neutrophil aggregates in preparing auxiliary diagnostic reagents for myasthenia gravis.

[0010] The myasthenia gravis auxiliary diagnostic reagent comprises a reagent for detecting CD62P and / or a reagent for detecting platelet-neutrophil aggregates.

[0011] The reagent for detecting CD62P refers to a reagent for detecting the level or content of CD62P in a subject; Preferably, the reagent for detecting the level or content of CD62P in a subject comprises: anti-human CD61 / CD41 antibody, anti-human CD62P antibody.

[0012] The reagent for detecting platelet-neutrophil aggregates refers to a reagent for detecting the level or content of platelet-neutrophil aggregates in a subject; Preferably, the reagent for detecting the level or content of platelet-neutrophil aggregates in a subject comprises: anti-human CD61 / CD41 antibody.

[0013] A myasthenia gravis auxiliary diagnostic reagent comprises: a reagent for detecting a marker; the marker is selected from: CD62P and / or platelet-neutrophil aggregates.

[0014] The reagents for detecting markers include: reagents for detecting the content or level of CD62P in a subject and / or reagents for detecting the content or level of PNAs in a subject.

[0015] Reagents for detecting the content or level of CD62P in a subject include: anti-human CD61 / CD41 antibodies and anti-human CD62P antibodies.

[0016] Preferably, the reagent for detecting the content or level of platelet-neutrophil aggregates in a subject comprises: anti-human CD61 / CD41 antibody.

[0017] Preferably, the auxiliary diagnosis includes: early screening, early warning, and clinical auxiliary diagnosis.

[0018] A myasthenia gravis auxiliary diagnosis system comprises: a detection unit and a calculation and analysis unit connected in sequence on a data main line; the detection unit detects the number of marker-positive cells and outputs the number of marker-positive cells to the calculation and analysis unit; the calculation and analysis unit outputs a first data branch when the percentage of the number of platelet cells positive for marker CD62P in the total number of platelets in peripheral blood is <8.9% and / or the percentage of platelet-neutrophil aggregates for marker is <4.29%; the calculation and analysis unit outputs to the downstream of the main line when the percentage of the number of platelet cells positive for marker CD62P in the total number of platelets in peripheral blood is ≥8.9% and / or the percentage of platelet-neutrophil aggregates for marker is ≥4.29%.

[0019] The myasthenia gravis auxiliary diagnosis system further comprises: a negative report output unit arranged downstream of the analysis unit on the main path; Preferably, the detection unit also detects the total platelet count and the total neutrophil count in the peripheral blood and outputs the total platelet count and the total neutrophil count in the peripheral blood to the calculation and analysis unit; Preferably, the myasthenia gravis auxiliary diagnosis system further comprises: a positive report output unit connected to the first data branch; Preferably, the data main path and the first data branch path are both data paths.

[0020] The present invention has the following outstanding beneficial effects: The present invention screened markers in several myasthenia gravis patients and healthy people collected clinically, and found that substances with different levels included CD62P and PNAs. The ratio of CD62P-positive platelets and PNAs was significantly increased in MG patients, which was closely related to the activity of myasthenia gravis disease. At the same time, the ROC curve verified that these two types of substances were suitable as candidate auxiliary diagnostic markers. Therefore, the present invention provides the use of CD62P and / or PNAs as auxiliary diagnostic markers for myasthenia gravis (MG). The present invention also provides the use of CD62P and / or PNAs in the preparation of auxiliary diagnostic reagents for myasthenia gravis based on the two auxiliary diagnostic markers CD62P-positive platelets and PNAs, and provides an auxiliary diagnostic system for myasthenia gravis, which assists in the diagnosis of myasthenia gravis by monitoring the ratio of CD62P-positive platelets and / or PNAs in the patient's blood, wherein the ratio of PNAs can assess its severity. The auxiliary diagnostic marker and auxiliary diagnostic system of the present invention can provide an important reference basis for early auxiliary diagnosis and disease monitoring of MG, and improve the accuracy and efficiency of clinical auxiliary diagnosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 The ROC curve of CD62P-positive platelets, an auxiliary diagnostic marker for MG, provided in one embodiment of the present invention.

[0022] Figure 2 The ROC curve of the MG auxiliary diagnostic marker PNAs provided by another embodiment of the present invention. DETAILED DESCRIPTION

[0023] The present invention is further described in detail below in conjunction with specific embodiments and experimental examples, but the embodiments of the present invention are not limited thereto, nor are the protection scope of the present invention limited thereto.

[0024] Sources of biological materials 1. The blood samples of 40 subjects used in Experimental Example 1 were collected from patients admitted to the applicant's unit. The public can obtain human blood samples through legal and normal channels to verify the technical effects of the present invention.

[0025] 2. The blood samples of 40 subjects used in Experimental Example 2 were collected from patients admitted to the applicant's unit. The public can obtain human blood samples through legal and normal channels to verify the technical effects of the present invention.

[0026] Group 1 Examples: Use of the Auxiliary Diagnostic Markers of the Present Invention This group of embodiments provides the use of CD62P and / or PNAs as auxiliary diagnostic markers for myasthenia gravis.

[0027] In a specific embodiment, the myasthenia gravis auxiliary diagnostic marker is selected from any one or two of CD62P and PNAs.

[0028] Any use of any one or two of CD62P and PNAs for the detection, early warning, prediction, diagnosis, prognosis, treatment, prevention and treatment of myasthenia gravis, or the preparation, production, sale, promise of sale, import or export of myasthenia gravis drugs, or the preparation, production, sale, promise of sale, import or export of myasthenia gravis diagnostic reagents falls within the scope of protection of the present invention.

[0029] The Chinese and English names of the markers herein have common technical meanings that can be conventionally understood by those skilled in the art, for example: CD62P can be the substance represented by the Baidu Encyclopedia entry "P-selectin", or it can be the meaning of "CD62P" recorded in the article "Analysis of the Mechanism of Vibrio vulnificus Hemolysin-Induced Platelet Activation"; PNAs may be the meaning of "platelet-neutrophil aggregates (PNA)" recorded in the article "Effects of Xuesetai combined with acupuncture and head scraping on brain CT blood perfusion imaging indicators, blood rheology and platelet-leukocyte aggregates in patients in the recovery period of cerebral infarction".

[0030] The second group of embodiments, use of the auxiliary diagnostic reagent of the present invention This group of embodiments provides the use of CD62P and / or PNAs in preparing auxiliary diagnostic reagents for myasthenia gravis.

[0031] In some embodiments, the myasthenia gravis auxiliary diagnostic reagent includes a reagent for detecting CD62P and / or a reagent for detecting PNAs.

[0032] In a specific embodiment, the reagent for detecting CD62P refers to a reagent for detecting the level or content of CD62P in a subject; Preferably, the reagent for detecting the level or content of CD62P in a subject comprises: anti-human CD61 / CD41 antibody, anti-human CD62P antibody.

[0033] Anti-human CD61 / CD41 antibodies are used to distinguish platelets from other blood components (such as red blood cells, white blood cells, etc.) and mark all platelets; anti-human CD62P antibodies are used to further confirm the activation state of platelets. By combining these two antibodies, activated platelets can be specifically detected. The gating logic of flow cytometry was based on the references "SK Popp et al., "Circulating platelet-neutrophil aggregates characterize the development of type 1 diabetes in humans and NOD mice", JCI Insight, Volume 7, Issue 2, Page e153993, January 2022, doi: 10.1172 / jci.insight.153993." and "S. Nhek et al., "Activated Platelets Induce Endothelial Cell Activation via an Interleukin-1β Pathway in Systemic Lupus Erythematosus", Arterioscler. Thromb. Vasc. Biol., Volume 37, Issue 4, Pages 707–716, April 2017, doi: 10.1161 / ATVBAHA.116.308126." The antibody manufacturer's catalog number is shown in Table 1 below.

[0034] Table 1

[0035] In a specific embodiment, the reagent for detecting PNAs refers to a reagent for detecting the level or content of PNAs in a subject; Preferably, the reagent for detecting the level or content of PNAs in a subject comprises: anti-human CD61 / CD41 antibody.

[0036] Neutrophils are distinguished from other white blood cells (such as lymphocytes or monocytes) based on the basic parameters of flow cytometry, forward scattered light (FSC) and side scattered light (SSC); anti-human CD61 / CD41 antibodies are used to specifically label platelets. Neutrophils with CD61 / CD41 (platelets) on their surface detected by flow cytometer fluorescent labeling technology are PNAs. The gate logic of flow cytometry is based on the reference "M. Ghorbani et al., "Platelet-Leukocyte Aggregate and Interleukin-6: An Emerging Perspective on a NewDiagnostic and Therapeutic Clue for Acute Coronary Syndrome, A Case-ControlStudy", Health Sci. Rep. , Volume 7, Issue 12, Page e70209, December 2024, doi: 10.1002 / hsr2.70209.” The antibody manufacturer’s catalog number is the same as shown in Table 1 above.

[0037] The third group of embodiments, the myasthenia gravis auxiliary diagnostic reagent of the present invention This group of embodiments provides an auxiliary diagnostic reagent for myasthenia gravis. All embodiments in this group have the following common features: the auxiliary diagnostic reagent for myasthenia gravis comprises: a reagent for detecting a marker; the marker is selected from: CD62P and / or PNAs.

[0038] In a specific embodiment, the reagent for detecting the marker includes: a reagent for detecting the content or level of CD62P in a subject and / or a reagent for detecting the content or level of PNAs in a subject.

[0039] In some embodiments, the reagent for detecting the content or level of CD62P in a subject comprises: anti-human CD61 / CD41 antibody, anti-human CD62P antibody.

[0040] Anti-human CD61 / CD41 antibodies are used to distinguish platelets from other blood components (such as red blood cells, white blood cells, etc.) and mark all platelets; anti-human CD62P antibodies are used to further confirm the activation state of platelets. By combining these two antibodies, activated platelets can be specifically detected. The gating logic of flow cytometry was based on the references "SK Popp et al., "Circulating platelet-neutrophil aggregates characterize the development of type 1 diabetes in humans and NOD mice", JCI Insight, Volume 7, Issue 2, Page e153993, January 2022, doi: 10.1172 / jci.insight.153993." and "S. Nhek et al., "Activated Platelets Induce Endothelial Cell Activation via an Interleukin-1β Pathway in Systemic Lupus Erythematosus", Arterioscler. Thromb. Vasc. Biol., Volume 37, Issue 4, Pages 707–716, April 2017, doi: 10.1161 / ATVBAHA.116.308126." The antibody manufacturer's catalog number is shown in Table 1 above.

[0041] Preferably, the reagent for detecting the content or level of PNAs in a subject comprises: anti-human CD61 / CD41 antibody.

[0042] Neutrophils are distinguished from other white blood cells (such as lymphocytes or monocytes) based on the basic parameters of flow cytometry, forward scattered light (FSC) and side scattered light (SSC); anti-human CD61 / CD41 antibodies are used to specifically label platelets. Neutrophils with CD61 / CD41 (platelets) on their surface detected by flow cytometer fluorescent labeling technology are PNAs. The gate logic of flow cytometry is based on the reference "M. Ghorbani et al., "Platelet-Leukocyte Aggregate and Interleukin-6: An Emerging Perspective on a NewDiagnostic and Therapeutic Clue for Acute Coronary Syndrome, A Case-ControlStudy", Health Sci. Rep. , Volume 7, Issue 12, Page e70209, December 2024, doi: 10.1002 / hsr2.70209.” The antibody manufacturer’s catalog number is the same as shown in Table 1 above.

[0043] Preferably, the auxiliary diagnosis includes: early screening, early warning, and clinical auxiliary diagnosis.

[0044] The fourth group of embodiments, the myasthenia gravis auxiliary diagnosis system of the present invention This group of embodiments provides a myasthenia gravis auxiliary diagnosis system. All embodiments of this group have the following common features: the myasthenia gravis auxiliary diagnosis system includes: a detection unit and a calculation and analysis unit connected in sequence on the data main line; the detection unit detects the number of marker-positive cells and outputs the number of marker-positive cells to the calculation and analysis unit; the calculation and analysis unit calculates that the percentage of the number of platelet cells positive for the marker CD62P in the total number of platelets in the peripheral blood is <8.9% and / or the percentage of the number of marker PNAs in the total number of neutrophils in the peripheral blood is <4.29%, and outputs the first data branch; the calculation and analysis unit calculates that the percentage of the number of platelet cells positive for the marker CD62P in the total number of platelets in the peripheral blood is ≥8.9% and / or the percentage of the number of marker PNAs in the total number of neutrophils in the peripheral blood is ≥4.29%, and outputs it to the downstream of the main line.

[0045] In a further embodiment, the myasthenia gravis auxiliary diagnosis system further includes: a negative report output unit disposed downstream of the analysis unit on the main path; Preferably, the detection unit also detects the total platelet count and the total neutrophil count in the peripheral blood and outputs the total platelet count and the total neutrophil count in the peripheral blood to the calculation and analysis unit; In some specific embodiments, the number of cells positive for the marker detected by the detection unit refers to: detecting the number of platelet cells positive for CD62P, and / or detecting the number of PNAs; In a more specific embodiment, detecting the number of CD62P-positive platelet cells refers to: detecting the number of CD62P-positive platelet cells in a blood sample collected from a subject using a flow cytometer; Detecting the number of PNAs means: using flow cytometry to detect the number of PNAs in a blood sample collected from a subject; Detection of the total platelet count in peripheral blood refers to: using a flow cytometer to detect the total platelet count in the peripheral blood of a blood sample collected from a subject; Detecting the total neutrophil count in peripheral blood refers to: using a flow cytometer to detect the total neutrophil count in peripheral blood in a blood sample collected from a subject.

[0046] In a specific embodiment, the CD62P-positive platelet cells have the common technical meaning known to those skilled in the art, and specifically can be the meaning of “CD62P-positive platelets” as described in the article “Naoxintong capsule limits myocardial infarct expansion by inhibiting platelet activation through the ERK5 pathway”; In other embodiments, the PNAs have the common technical meanings known to those skilled in the art, and specifically can be the meaning of “platelet-neutrophil aggregates” as described in the article “Platelet-Neutrophil aggregate formation induces NLRP3 inflammasome activation in VITT”; In some embodiments, the total peripheral blood platelet has the common technical meaning well known to those skilled in the art, and specifically may be the meaning of “peripheral blood platelet count” as described in the article “Platelet stimulation-regulated expression of ILK and ITGB3 contributes to intrahepatic cholangiocarcinoma progression through FAK / PI3K / AKT pathway activation”; In other embodiments, the total peripheral blood neutrophil count has the common technical meaning well known to those skilled in the art, and specifically may be the meaning of “peripheral blood neutrophil count” as described in the article “Expression of Siglec-9 in peripheral blood neutrophils was increased and associated with disease severity in patients with AECOPD”; Preferably, the myasthenia gravis auxiliary diagnosis system further comprises: a positive report output unit connected to the first data branch; Preferably, the data main path and the first data branch path are both data paths.

[0047] In a specific embodiment, the data path is selected from a wired form or a wireless form, for example, it can be a wired path, line, cable, or it can be a wireless path, wireless network, wifi connection, wireless channel, etc.

[0048] Experimental Example 1: Verification of the Accuracy of the Auxiliary Diagnosis of the Marker CD62P of the Present Invention This experimental example verifies the accuracy of the marker CD62P in assisting the diagnosis of myasthenia gravis. A total of 40 subjects were collected. The proportion of CD62P-positive platelets in the total platelets in the peripheral blood was detected. A total of 24 subjects had a CD62P-positive platelet ratio higher than 8.9%, and were evaluated as positive for myasthenia gravis; among these 24 subjects, 18 were clinically diagnosed as myasthenia gravis, indicating that in terms of positive auxiliary diagnosis of myasthenia gravis, the accuracy of the CD62P-positive platelet marker and the auxiliary diagnosis system of the present invention was 75%; the proportion of CD62P-positive platelets in 16 subjects was lower than 8.9%, and they were evaluated as negative for myasthenia gravis. Among these 16 subjects, 14 were clinically diagnosed as negative for myasthenia gravis, indicating that in terms of negative auxiliary diagnosis of myasthenia gravis, the accuracy of the CD62P marker and the auxiliary diagnosis system of the present invention was 87.5%; the diagnostic comparison results of some subjects are shown in Table 2 below: Table 2 Case number CD62P marker aids diagnosis Clinical criteria for the diagnosis of myasthenia gravis 1 Negative Positive 2 Positive Positive 3 Positive Positive 4 Positive Positive 5 Positive Positive 6 Positive Positive 7 Positive Positive 8 Positive Positive 9 Positive Positive 10 Positive Positive 11 Negative Negative 12 Negative Negative 13 Positive Negative 14 Negative Negative 15 Negative Negative 16 Negative Negative 17 Negative Negative 18 Positive Negative 19 Positive Negative 20 Negative Negative Experimental Example 2: Verification of the Accuracy of Auxiliary Diagnosis of the PNAs of the Present Invention This experimental example verifies the accuracy of the marker PNAs for auxiliary diagnosis of myasthenia gravis. A total of 40 subjects were collected. The proportion of PNAs in the total number of neutrophils in peripheral blood was detected. A total of 24 subjects had a PNA ratio higher than 4.29%, and were evaluated as positive for myasthenia gravis; among these 24 subjects, 18 were clinically diagnosed as myasthenia gravis, indicating that in terms of positive auxiliary diagnosis of myasthenia gravis, the accuracy of the PNAs marker and auxiliary diagnosis system of the present invention was 75%; the PNA ratio of 16 subjects was lower than 4.29%, and they were evaluated as negative for myasthenia gravis. These 11 subjects were also clinically diagnosed as negative for myasthenia gravis, indicating that in terms of negative auxiliary diagnosis of myasthenia gravis, the accuracy of the PNAs marker and auxiliary diagnosis system of the present invention was 68.75%; the diagnostic comparison results of some subjects are shown in Table 3 below: Table 3 Case number PNAs as diagnostic markers Clinical criteria for the diagnosis of myasthenia gravis 1 Positive Positive 2 Positive Positive 3 Positive Positive 4 Positive Positive 5 Positive Positive 6 Positive Positive 7 Positive Positive 8 Positive Positive 9 Positive Positive 10 Positive Positive 11 Negative Negative 12 Negative Negative 13 Negative Negative 14 Positive Negative 15 Positive Negative 16 Negative Negative 17 Negative Negative 18 Negative Negative 19 Negative Negative 20 Negative Negative In Experimental Examples 1 and 2, the clinical diagnostic criteria for myasthenia gravis are: meeting the clinical characteristics of MG (fluctuating muscle weakness and fatigability, aggravated by continuous activity and relieved by rest), meeting the positive AChR antibody test (radioimmunoassay), pharmacological examination (neostigmine test) and electrophysiological characteristics that meet the diagnostic criteria for MG (repetitive frequency electrical stimulation test with a decrease of more than 10% in the amplitude of low-frequency stimulation; widening of the "tremor" of the single fiber electromyogram, with or without block).

[0049] Experimental Example 3: Clinical severity assessment of MG patients The marker PNAs of the present invention can also be used to assess the clinical severity of MG patients. Clinically, the clinical severity of MG patients is assessed by quantitative MG score (QMGs). The results of the ratio of QMGs and PNAs to the total number of neutrophils in peripheral blood of some subjects are shown in Table 4 below.

[0050] Table 4 Case number QMG The proportion of PNAs to the total number of neutrophils in peripheral blood (%) 1 0 5.6 2 9 10.7 3 9 9.23 4 5 9.83 5 7 6.72 6 4 4.85 7 8 4.72 8 15 11 9 7 7.36 10 6 5.18 11 11 7.68 12 10 5.68 13 7 6.25 14 13 11.3 15 0 11.7 16 11 9.63 17 14 11.9 18 8 4.33 19 3 7.06 20 11 10.5 21 6 5.4 22 11 14.8 23 7 7.63 24 14 9.5 25 5 7.57 26 9 4.98 Pearson correlation analysis results: r = 0.4210, p = 0.0322.

Claims

1. Use of CD62P and / or platelet-neutrophil aggregates as auxiliary diagnostic markers for myasthenia gravis.

2. Use of CD62P and / or platelet-neutrophil aggregates in the preparation of auxiliary diagnostic reagents for myasthenia gravis.

3. Use of the CD62P and / or platelet-neutrophil aggregates according to claim 2 in the preparation of an auxiliary diagnostic reagent for myasthenia gravis, characterized in that: The myasthenia gravis auxiliary diagnostic reagent comprises a reagent for detecting CD62P and / or a reagent for detecting platelet-neutrophil aggregates.

4. Use of the CD62P and / or platelet-neutrophil aggregates according to claim 3 in the preparation of an auxiliary diagnostic reagent for myasthenia gravis, characterized in that: The reagent for detecting CD62P refers to a reagent for detecting the level or content of CD62P in a subject; And / or, the reagent for detecting the level or content of CD62P in the subject includes: anti-human CD61 / CD41 antibody, anti-human CD62P antibody.

5. Use of the CD62P and / or platelet-neutrophil aggregates according to claim 3 in preparing an auxiliary diagnostic reagent for myasthenia gravis, characterized in that: The reagent for detecting platelet-neutrophil aggregates refers to a reagent for detecting the level or content of platelet-neutrophil aggregates in a subject; And / or, the reagent for detecting the level or content of platelet-neutrophil aggregates in a subject includes: anti-human CD61 / CD41 antibody.

6. A myasthenia gravis auxiliary diagnostic reagent, characterized in that: include: A reagent for detecting a marker; the marker is selected from: CD62P and / or platelet-neutrophil aggregates.

7. The myasthenia gravis auxiliary diagnostic reagent according to claim 6, characterized in that: The reagents for detecting markers include: reagents for detecting the content or level of CD62P in a subject and / or reagents for detecting the content or level of PNAs in a subject.

8. The myasthenia gravis auxiliary diagnostic reagent according to claim 7, characterized in that: Reagents for detecting the content or level of CD62P in a subject include: anti-human CD61 / CD41 antibodies, anti-human CD62P antibodies; and / or, the reagent for detecting the content or level of platelet-neutrophil aggregates in the subject includes: anti-human CD61 / CD41 antibody; And / or, the auxiliary diagnosis includes: early screening, early warning, and clinical auxiliary diagnosis.

9. A myasthenia gravis auxiliary diagnosis system, characterized in that: include: The detection unit and the calculation and analysis unit are sequentially connected on the data main line; The detection unit detects the number of cells that are positive for the marker and outputs the number of cells that are positive for the marker to the calculation and analysis unit; the calculation and analysis unit outputs the first data branch when the percentage of the number of platelet cells that are positive for the marker CD62P in the total number of platelets in the peripheral blood is <8.9% and / or the percentage of the marker platelet-neutrophil aggregates in the total number of neutrophils in the peripheral blood is <4.29%; the calculation and analysis unit outputs it to the downstream of the main path when the percentage of the number of platelet cells that are positive for the marker CD62P in the total number of platelets in the peripheral blood is ≥8.9% and / or the percentage of the marker platelet-neutrophil aggregates in the total number of neutrophils in the peripheral blood is ≥4.29%.

10. The myasthenia gravis auxiliary diagnosis system according to claim 9, characterized in that: Also includes: A negative report output unit disposed downstream of the analysis unit on the main route; And / or, the detection unit further detects the total platelet count and the total neutrophil count in the peripheral blood and outputs the total platelet count and the total neutrophil count in the peripheral blood to the calculation and analysis unit; And / or, the myasthenia gravis auxiliary diagnosis system further comprises: a positive report output unit connected to the first data branch; And / or, the data main path and the first data branch path are both data paths.

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