STUDY OF IMMUNOGENETIC PATHOGENESIS OF CHILDHOOD-ONSET MYASTHENIA GRAVIS

儿童发病重症肌无力的免疫遗传发病机制研究

• 批准号: 07670912
• 负责人: SHINOMIYA Noriaki
• 金额: $ 1.47万
• 依托单位: TOHO UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670912/
• 关键词: Childhood-onset myasthenia gravis; HLA-DRB1^<**>0901; HLA-DQ; HLA-DPB1^<**>0201; acetylcholine receptor; T-cell repatoire; antigenic peptide; T cell receptor (TCR) alphabeta chain; 抗acetylcholine receptor抗体; 潜在性全身型; HLA-DRB1^※0901; HLA-DRB1^※13

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

由于大多数儿童期发病的 MG 患者的抗 AChR 自身抗体滴度较低或呈阴性，因此抗 AChR 自身抗体作为肌无力原因的作用仍然是一个悬而未决的问题。日本儿童期发病的 MG 患病率中，最大的发病年龄组为 3 岁以下，该年龄组的大多数患者具有潜伏一般型 (LG) 的临床特征。免疫反应紊乱作为LG型的致病原因发挥着重要作用。采用PCR/SSO方法分析儿童期发病的MG患者HLA-DRB、DQ或DP等位基因的表达频率。在儿童期发病时，DRB1^<**>0901-DQA1^<**>0301-DQB1^<**>0303、DRB1^<**>1302-DQA1^<**>0102-DQB1^<**>0604 或 DPB1^<**>2010 的表达存在显着相关性 MG.DRB1^<**>0901 被认为是重要的抗原肽结合位点，是 AChR 高反应 T 细胞系增殖抑制测定的基础（提交中……更多 n）。这些高度多态性的 HLA-II 类蛋白充当来自抗原加工的抗原肽的结合位点，并将其呈递给抗原特异性 CD4+ T 细胞，并对 T 细胞库的特异性发挥关键作用。由于MHC分子与抗原肽的结合影响成熟T细胞库的特异性，我们推测，在LG型儿童发病的MG患者和成人发病的MG患者之间观察到的HLA DRB1类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。在本研究中，将来自儿童期发病 LG 型 MG 的 AChR 高反应性 T 细胞系的 T 细胞受体 (TCR) 字母链库与高 AChR 抗体滴度的成人发病 MG 的 T 细胞系进行比较。目前的结果表明，MG 患者的潜在一般类型是基于与 DPB1^<**>0901 表达强相关性的特征亚型。较少的

项目成果

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