2000 Fiscal Year Final Research Report Summary
Study for mechanism of autoantibody production in myasthenia gravis
| Project/Area Number |
09670647
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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 |
Neurology
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| Research Institution | Kanazawa University |
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Principal Investigator |
YOSHIKAWA Hiroaki Kanazawa University Health Service Center, Associate Professor, 保健管理センター, 助教授 (10272981)
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| Project Period (FY) |
1997 – 2000
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| Keywords | Myasthenia gravis / Acetylcholine receptor / Anti-acetylcholine receptor antibody / Autoimmune disease / Thymus / Bone marrow / Peripheral blood lymphocytes / IgG |
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| Research Abstract |
1. T cell-specific immunosuppressive agent ; FK506 prevents induction of rat experimental autoimmune myasthenia gravis (EAMG) evoked by immunizing T cells against the synthetic peptide which corresponds to human acetylcholine receptor (AChR) α-subunit residues 125-147 (Hα125-147).
2. The thymus in a majority of patients with acquired myasthenia gravis (MG) is the principal but not the sole reservoir of immunocytes that specifically react with muscle antigens.
3. The α-subunit segment 125-147 (Nα125-147) of the nicotinic acetylcholine receptor of human skeletal muscle (AChR) is stimulatory for lymph node T cells of immunized Lewis rats, and induces autoantibody production and clinical and electrophysiological signs of EAMG.The goal of this study was to identify and modify in this autoantigen the minimal epitope (s) necessary for helper T cell activation and disease induction. We identified Hα129-145 as a minimum epitope. The analog peptide with alanine substituted for phenylalanine 137 may have therapeutic potential because it is equivalent to the native peptide in its binding to MHC class II, but fails to stimulate a T cell proliferative response, and is therefore a candidate T cell receptor antagonist.
4. Thymocytes form MG patients were transferred into the peritoneal cavities of severe combined immunodeficiency (SCID) mice, which caused the mice to produce human IgG and IgM.The injected thymocytes were then recovered from the peritoneal cavities of MG-SCID mice. The functional human T and B cells survived in the SCID mice for a long period.
5. Peripheral blood mononuclear cells (PBMC) from MG patients is the most efficient site at producing AChRAb amongst thymocytes, bone marrow (BM) cells and PBMC, even in patients of short duration (equal to, or less than, 2 months). Monitoring AChRAb secretion by PBMC is useful to estimate the autoimmune activity of MG.
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