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The Detection of Antibodies Against Postsynaptic Membrane at Neuromuscular Junction and the Study of Clinical Characteristics in Myasthenia Gravis

Author: FanXin
Tutor: YangLi
School: Tianjin Medical University
Course: Neurology
Keywords: Myasthenia gravis Acetylcholine receptor antibody Anti- muscle-specific receptor tyrosine kinase antibody Fluorescent immunoprecipitation
CLC: R746.1
Type: Master's thesis
Year: 2009
Downloads: 17
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Abstract

Objective: myasthenia gravis (MG) is an antibody-mediated autoimmune disease, approximately 85% of patients with serum acetylcholine receptor antibody (AChR-Ab) positive. Currently found in AChR-Ab negative serum anti-muscle-specific receptor tyrosine kinase antibody (MuSK-Ab), which inhibit development AChR aggregation of the postsynaptic membrane, closely associated with the pathogenesis of myasthenia gravis. Fluorescent immunoprecipitation method to detect the serum of patients with myasthenia gravis AChR-Ab, MuSK-Ab level summary of the inclusion of patients with clinical information, compare AChR-Ab positive MuSK-Ab-positive as well as negative serum antibody (SNMG) in patients with myasthenia gravis. The clinical features. Method: 1, fluorescent immunoprecipitation method MuSK / AChR plasmid polyethylene imine (PEI) for medium transfected HEK293 cells, select the best PEI / DNA optimize than to improve the efficiency of transfection. Antigen extracts obtained with serum combined to form a precipitate, read fluorescence plate reader fluorescence value (FU), to the healthy control group, the average (FU) three times the standard deviation (SD) prevail line above this value is considered MuSK-Ab/AChR-Ab positive. 2 serum and clinical information, collected 103 cases of clinically diagnosed patients with myasthenia gravis, detect AChR-Ab and MuSK-Ab levels in the serum of patients. Summary of AChR-Ab positive MuSK-Ab-positive and serum antibody-negative patients (SNMG) clinical features. Results: The collection of 103 cases of patients with myasthenia gravis, from 13 years old to 78 years old can be the onset, gender distribution was no significant difference. The women starting average age was 44.9 (18.1) the the male average starting age was 45.8 (16.2), 50% of patients with onset between the ages of 40-59 years old. Extraocular muscle paralysis is the most important first symptom (86.2%), is the most common clinical manifestations (96.1%). Limb muscle weakness and bulbar muscle weakness as the first symptoms of the patients were 7.4% (8/103) and 6.4% (6/103). 42.7% (44/103) of patients showed simple extraocular muscle involvement, and 57.3% (59/103) of patients showed extensive involvement muscles. 103 patients, the detection AChR-Ab positive rate of 71.8% (74/103), which simply extraocular muscle involvement MG (MGFA I type) AChR-Ab positive rate was 50% (20/40), involving the whole body muscle weakness, MG (MGFA other type) AChR-Ab positive rate was 85.7% (54/63). Five cases MuSK-Ab-positive serum AChR-Ab negative, positive AChR-Ab-negative patients was 17% (5/29). AChR-Ab-positive patients with MuSK-Ab positive and negative serum antibody (SNMG), age, gender, and the first symptom was no significant difference. MuSK-Ab-positive patients bulbar muscular involvement AChR-Ab positive group of patients than SNMG group of bulbar muscle weakness (60%), the percentage of patients than the the SNMG group (8.3%) (P = 0.02); (P = 0.001). Limbs involvement in patients with AChR-Ab-positive group (47.8%), as compared to the the SNMG group difference was significant (P = 0.008). SNMG patients mainly external ophthalmoplegia. MGFA grading standards and quantitative score (QMG) to be judged by the degree of the patient's condition, SNMG I type (simple extraocular muscle involvement) accounted for about 75% of patients (18/24), compared with AChR-Ab positive, MuSK-Ab-positive group (P = 0.001); the highest percentage of serum AChR-Ab positive group Ⅱ patients (60.8%, P = 0.013); ≥ III patients with MuSK-Ab-positive group compared with the other two groups, the share of the proportion of maximum (40%, P = 0.023). MuSK-Ab-positive patients with MuSK-Ab titers with QMG score related (r = 0.949, P = 0.014), regardless of the AChR-Ab titers with the severity of the disease. Patients (thymoma / thymic hyperplasia) associated with thymic lesions accounted for 41.7% (43/103), thymoma incidence of 22.3% (23/103), thymic hyperplasia incidence of 19.4% (20/103) . We found that MuSK-Ab-positive patients does not appear thymoma or thymic hyperplasia, thymoma and thymic hyperplasia AChR-Ab-positive group and SN-MG group positive rate of 23%, 27% and 12.5%, 12.5% . Patients with myasthenia gravis associated with thymoma or thymic hyperplasia AChR-Ab positive rate of 87% and 85% higher simplex myasthenia gravis AChR-Ab positive rate was 61.7% (P = 0.025). Conclusion: Severe weakness predilection age of 40-59 years old, male and female distribution was no significant difference. Extraocular muscle paralysis is the most important first symptom, the most common clinical manifestations, concomitant limb muscle and bulbar muscular body muscles extensive involvement. AChR-Ab positive rate was 71.8%, simple extraocular muscle involvement AChR-Ab positive rate was 50%, 85.7% involving patients with generalized muscle weakness. MuSK-Ab only appear in the serum AChR-Ab-negative patients, the detection rate of 17%. MuSK-Ab-positive patients mainly bulbar muscular involvement MuSK-Ab titers with the severity of the disease related, MuSK- Ab-positive patients is not associated with lesions of the thymus. AChR-Ab-positive patients with limb muscle involvement is more common typing mainly type Ⅱ Ⅱ most common type b, combined with higher thymic lesions in patients with AChR-Ab positive rate. The SNMG mild symptoms, mainly simple extraocular muscle involvement, MGFA parting type Ⅰ.

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