Expression Of M3 Receptors In Thymus Of Different Pathological Types In Patients With Myasthenia Gravis And Its Relationship With Prognosis

Background and ObjectiveMyasthenia gravis(MG)is an autoimmune disease mainly mediated by antibodies,complement participation,and involvement of the neuromuscular junction(NMJ),and the patients always have structural or functional abnormalities of the thymus.Non-neuronal Cholinergic System(NNCS)is widely expressed in various tissues including thymus.Previous studies found that α1,α9,M3,α2,and β2 receptors were abnormally expressed in thymus tissue of MG patients,and the expression of α1,α9,α2,and β2 receptors in thymus of different pathological types in patients with MG has been tested,but the expression of M3 receptors has not yet been determined.Muscarinic acetylcholine receptors(mAChRs)M3 can cause changes in the number or function of immune cells by mediating Ca2+signaling in lymphocytes and triggering nuclear signaling,which may be related to the pathogenesis of MG.In this study,we examined the expression of M3 receptors in the thymus of MG patients with different pathological types and analyzed their correlations with surgical prognosis.We aimed to explore the role of M3 receptors in the pathogenesis of MG and provide new ideas for the diagnosis and treatment of MG.Materials and Methods1.General clinical date:From August,2012 to June,2018,145 patients with MG who underwent thymectomy and had complete medical records in the Department of Thoracic Surgery,the Second Affiliated Hospital of Zhengzhou University were collected,and we searched the basic information and exam results of all patients.The control group selected 15 patients who underwent cardiac surgery in our hospital during the same period.2.The expression of M3 receptors in thymus of different pathological types:The thymus tissue of patients and control group were made into paraffin sections.The expression of M3 receptors in thymus of different pathological types were detected by immunohistochemical techniques,and the scores were given according to the staining rate and degree of staining.3.Correlation analysis between the expression of M3 receptors in thymus of different pathological types and prognosis:According to MGFA’s post-intervention status assessment criteria,the prognosis of patients was followed up in order to assess the correlations between the expression of M3 receptors in thymus of different pathological types and prognosis.4.Statistical analysis:The data involved in this study were processed by SPSS21.0 software.The t-test was used for the comparisons between groups of data that meet the normal distribution,and the rank-sum test was used for data that do not meet the normal distributions.The correlations of categorical variables were analyzed by the chi-square test or Fisher exact test.Inspection level α=0.05.ResultsA total of 145 patients with MG were enrolled,including 65 patients with thymoma,25 patients with thymic hyperplasia,and 55 patients with thymic atrophy.The M3 receptors were expressed in the thymus of different pathological types in patients with MG and in the control group,mainly distributed in the cell membrane and cytoplasm,and a small amount in the nucleus.The expression of M3 receptors in proliferative thymus and thymoma was much lower than that in the control group(p<0.05),and there was no significant difference in the expression of M3 receptors between atrophic thymus and normal thymus(p>0.05).120 patients were followed up for 7 to 77 months,with a median follow-up time of 50 months.The complete stable remission rate was 28.3%,the total clinical remission rate(CSR+PR+MM)was 72.5%,and the total effective rate(CSR+PR+MM+1)was 89.2%.Correlation analysis was performed between the expression levels of M3 receptors in the thymus of different pathological types and the prognosis.The results showed that the expression of M3 receptors in proliferative thymus was negatively correlated with the patients’ complete remission(p<0.05),and the expression of M3 receptors in atrophic thymus and thymoma had no significant correlation with the patients’ complete remission(p>0.05).Conclusions(1)The M3 receptors were abundantly expressed in the thymus of different pathological types in patients with MG and in the control group,mainly distributed in the cell membrane and cytoplasm,and a small amount in the nucleus.(2)The expression of M3 receptors in the thymus of different pathological types in patients with MG were different.The expression of M3 receptors in hyperplastic thymus and thymoma tissue was much lower than that in the control group,and there was no significant difference in the expression of M3 receptors between atrophic thymus and normal thymus.(3)The expression level of M3 receptors in proliferative thymus was negatively correlated with the prognostic,and the expression of M3 receptors in atrophic thymus and thymoma had no significant correlation with prognosis.This difference in the expression of M3 receptors may play an important role in the pathogenesis of MG by affecting the apoptosis mechanism of cells.