The Clinical Significances Of Expressions Of Muscle Antigen In Thymus And Change Of Anti-Muscle Antibody In MG Patients

Myasthenia gravis (MG) is a kind of autoimmue disease with the characteristic of the dysfunctional neuromuscular transmission. The explanation of it's etiology focuses on the antibodies against the skeletal antigens involving AChR-ab. However recent study discovered that the skeletal antigen in normal skeletal cells could not induce the secretion of any related antibody, nor did the nicotine AChR antigen on the post synapse membrane. The following findings suggested the thymus in the MG patients might express some components of skeletal antigen stimulating B cell to secret autoimmue antibody under the help of APC in the thymus. These findings can be concluded as: 1. Pathological findings could always be uncovered in the MG thymus, in that lymph foilicie hyperplasia could be found in 70% of them, thymoma in 15% and thymus hypoplasia in 10%; 2. Approximately 88.7% of the MG patients could achieve prominent symptom release after thymectomy; 3. The titer of AChR-ab would significantly decrease after thymectomy. To make a further study on the etiology of MG as well as explore the theory basis for thymectomy, this protocol tended to examine the expression of skeletal antigen and AChR, measure the titer of multiple anti-muscle antibody as well as the AChR-ab in the peripheral blood plasma, analyze the possible relation between clinical symptoms and the etiological antigen and antibodies which might take a part in the pathological process of the MG. Via light scope and eletronic microscope the pathologic changes and ultromicro -structure were observed, indicating prominent difference between MG thymus and the normal contral. A prominent characteristic is the hyperplasia of thymic myoid cells. Immunohistochemistry was performed in these cells to detect the antigen of Myosin, desmin and AChR which might take a part in stimulating the autoimmne reaction against AChR. RT-PCR was applied to detect the transcripts of genes coding AChR subuits, which indicated the structure of AChR in thymus cell. Though it has been well established that the AChR-ab is the key etiologic factor causing MG, the titer of AChR-ab in plasma dose not cmpletely macth the sever dgree of MG, indicating the effects of other etiologic factors such as the Myosin-ab. Since thymectomy has been regarded as the effective method to treat MG it is very essential to make it clear that whether it can improve the immune status in the MG patients. Using ELISA the plasma AChR-ab and Myosin-ab were detected. These results combined with other clinic pathological data were analyzed and compared to find out the clinic meaning of these two antibodies and the impaction of thymectomy on immnue status. Using western-blot the expression of skeletal antigen protein was quantified and their relation with the plasma antibody titer were studied. The prognostic implication of these antigens was also discussed. The release rate after thymectomy, gender, age, Osseman classification as well as the duration of MG symptoms prio to operation were all statistically analyzed vi X2 test to explore their relation. Main results and comments: 1. Plenty of hyperplasia blood capillary hyperplasia, prominent germinal centers and lymph foilicie were unvovered under the light scope. Scattered plasma cells were identified by electronic miceroscope containing many circular and equal sized immune secretory granule covered by membrana limitans. The similar secretory granules were also found outside these cells. In the 38 slides skeletal muscle protein was examined by immunohistochemistry stain, the numbers of pasitive cells were added via counting 10 obserbing sights. AChR significantly increased from 12.30±1.75 in the contral tissues to 33.05±2.48 in the MG thymus.Myosin significantly increased from 11.05±1.43 in the contral tissues to 25.03±2.51 in the MG thymus. Desmin significantly increased from 9.05±1.39 to 24.76±2.10 in the MG thymus. The AChR subunits of a+, a-,ε, β,γ,δin the MG thymus were all significantly highter than that in the normal contral tissues.These results proved the thymus as a target organ the autoimmune antibodies would attack. The abnormally increased expression of skeletal muscle antigen might excess the threshold of autotolerance playing an important role in the etiology of MG. 2. As to the level of plasma AChR-ab, through the analysis of 63 cases of MG, type Ⅰ(0.32±0.052)was significantly lower compared to IIa (0.41±0.051) and Ⅱb (0.42±0.054). The expression of AChR-ab varied significantly among different pathological types of MG--it was significantly higher in the myoma tissues compared to that in hyperplasiatissues(P<0.05);Afte thymectomy the AChR-ab decreased significantly especially in the patients with thymus hyperplasia. 3. Myosin is a component of thin filament. Its antibody, Myosin-ab, was significantly lower (P<0.05) in type I MG(0.27±0.032)compared to that in typeⅡa MG (0.39±0.061) or typeⅡb (0.40±0.042). Myosin-ab in patients of thymoma was significantly higher than that in patients of thymus hyperplasia (P<0.05). A significant relationship was uncovered between Myosin-ab and AChR-ab, in that the titer of Myosin-ab significantly decreased after thymectomy, especially in the patients with thymoma. The decrease of Myosin-ab was more significant than AChR-ab, indicating the level of plasma Myosin-ab was positively correlated with the theroputic effects of thymectomy, and the level of Myosin-ab could be much more easier to reflect the theraputic effects. 4. Multifactor analysis of 216 patients with simple MG showed that the CR and RR in 1, 3 and 5 years after operation was 21.2%,43.0%,43.4% and 87.6%,91.9%,92.1% respectively. A delayed respones occurred in the treatment of MG indicating long-term follow-up. The theraputic effect of thymectomy was significantly related with the duration of symptoms prio to operation and the Osserman classification, not related with the age and the pathological types. 5. AChR and Myosin were discovered to be overexpressed in MG tissues compared to normal contral, indicating that the antigen was so overexpressed in the MG tissues that it excessed the threshold of autotolerence. This might be a possible reason for the etiology of MG. So the theraputic effects of thymectomy might lie in the elimination of overexpressed T cell-related autoantigen.