| Project/Area Number |
07670912
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | TOHO UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
SHINOMIYA Noriaki TOHO UNI.SCHOOL OF MEDICINE,ASSOCIATE PROF., 医学部, 助教授 (10104225)
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| Co-Investigator(Kenkyū-buntansha) |
SEGAWA Masaya TOHO UNI.SCHOOL OF MEDICINE,VISITING ASSISTANT PROF., 医学部, 非常勤講師
KAZAMA Hiromi TOHO UNI.SCHOOL OF MEDICINE,INSTRUCTOR, 医学部, 助手 (90224386)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | 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^※1302 / AChR特異的ヘルパーT細胞 / TCRVレパトリ- / 小児発症重症筋無力症 / HLA-DRタイプ / アセチルコリン・リセプター抗原 / AChR抗原特異的T細胞 |
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| Research Abstract |
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
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