STUDY OF IMMUNOGENETIC PATHOGENESIS OF CHILDHOOD-ONSET MYASTHENIA GRAVIS

由于大多数儿童期发病的MG患者抗achr自身抗体滴度低或阴性，抗achr自身抗体在肌无力中的作用仍是一个悬而未决的问题。日本儿童期MG患病率以3岁以下发病人群最多，且该年龄段患者多表现为潜伏性一般（LG）型。免疫应答紊乱是LG型发病的重要原因。采用PCR/SSO方法分析儿童发病MG患者HLA-DRB、DQ或DP等位基因的表达频率。DRB1^<**>0901-DQA1^<**>0301-DQB1^<**>0303、DRB1^<**>1302-DQA1^<**>0102-DQB1^<**>0604、DPB1^<**>2010在儿童期发病MG中的表达有显著相关性。DRB1^<**>0901被认为是重要的抗原肽结合位点，是achr高反应T细胞系增殖抑制实验的基础（已提交…More n）。这些高度多态性的hla - II类蛋白作为抗原加工产生的抗原肽的结合位点，并将其呈递给抗原特异性的CD4+ T细胞，在T细胞修复的特异性中起着关键作用。由于MHC分子与抗原肽的结合影响成熟t细胞库的特异性，我们认为LG型儿童期发病MG患者与成年期发病MG患者HLA DRB1型表达频率的差异表明两组MG患者的AChR抗原肽存在差异。本研究比较了LG型儿童期发病MG与成年期高AChR抗体滴度MG的高AChR反应性T细胞系的T细胞受体(TCR) α链修复。本研究结果表明，MG患者的潜在一般型是一种特征性亚型，与DPB1^<**>0901表达密切相关。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