STUDY OF IMMUNOGENETIC PATHOGENESIS OF CHILDHOOD-ONSET MYASTHENIA GRAVIS

由于儿童期发病的MG患者大多数抗AChR自身抗体滴度低或阴性，抗AChR自身抗体作为肌无力的原因的作用仍然是一个悬而未决的问题。至于儿童期发病的MG在日本的患病率，发现最大的发病年龄组在3岁以下，并且该年龄组的大多数患者具有潜伏全身（LG）型的临床特征。免疫功能紊乱是LG型的重要致病因素。采用PCR/SSO方法分析HLA-DRB、DQ、DP等位基因在儿童期MG患者中的表达频率。在DRB 1 ^**>0901-DQA 1 ^**>0301-DQB 1 ^**> 0303，DRB 1 ^**>1302-DQA 1 ^**>0102-DQB 1 ^**>0604，DRB 1 ^**>0901被认为是重要的AChR-高-应答性T细胞系（提交 ...更多信息 n）。这些高度多态性的HLA-II类蛋白作为抗原肽的结合位点发挥功能，这些抗原肽来源于抗原的加工，并将它们呈递给抗原特异性的CD 4 + T细胞，并且对T细胞抗原表位的特异性起关键作用。由于MHC分子与抗原肽的结合影响了成熟T细胞库的特异性，我们推测，在儿童期发作的MG和成人发作的MG的LG型患者之间观察到的HLA-DRB 1型表达频率的差异表明，来自AChR的抗原肽在两组MG患者之间是不同的。本研究比较了儿童型MG和成人型MG的AChR高反应性T细胞系的TCR α链。目前的结果表明，MG患者的潜伏一般型是基于与DPB 1 * 0901表达的强关联的特征亚型。少

As most MG patients with childhood onset have low or negative anti-AChR autoantibody titer, the role of anti-AChR autoantibody as the cause of muscle weakness remains as the open question. As for the prevalence of childhood-onset MG in Japan, the largest onset-age group was found to be under three years, and most patients of this age group had the clinical characteristic the latent general (LG) type. The disturbance in immune responses plays the important role as the pathogenic causes in the LG type. The expression frequencies of HLA-DRB,DQ or DP alleles in patients with childhood-onset MG was analyzed using PCR/SSO method. A significant correlation was observed in the expression of DRB1^<**>0901-DQA1^<**>0301-DQB1^<**>0303, DRB1^<**>1302-DQA1^<**>0102-DQB1^<**>0604, or DPB1^<**>2010 in the childhood-onset MG.DRB1^<**>0901 is considered to be important as antigenic peptide binding site of basis of the proliferation inhibition assay of the AChR-high-responsive T cell lines (in submissio … More n). These highly polymorphic HLA-class II proteins function as binding sites to antigenic peptides derived from the processing of antigens and present them to antigen-specific CD4+ T cells, and plays the pivotal roles for the specificity of the T-cell repatoire. As the binding of MHC molecule with antigenic peptide influences the specificity of the mature T-cell repertoire, we suppose that the difference in HLA DRB1 type expression frequency observed between LG type patients with childhood-onset MG and those with adult-onset MG suggest that the antigenic peptides from AChR are different between two groups of MG patients. Under the present study, T cell receptor (TCR) alphabeta chain repatoires from the AChR-high-responsive T cell lines of LG type of childhood-onset MG are compared with those with adult-onset MG of high AChR antibody titer. The present results demonstrate that the latent general type of MG patients is a characteristic subtype on the basis of a strong association to DPB1^<**>0901 expression. Less