| Project/Area Number |
06454296
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
YATA Junichi Tokyo Medical and Dental University, School of Medicine, Professor, 医学部, 教授 (60057502)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1996: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | severe combined immunodeficiency / hyper-IgM syndrome / Wiskott-Aldrich syndrome / gene abnormality / mast cell / Fcepsilon receptor / allergy / 接着分子 / 遺伝子異常 / インターロイキン4 / IgE / IL-2レセプターγ鎖 / 免疫グロブリン遺伝子 / B細胞 / Fcεレセプター / IL-4 |
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| Research Abstract |
Pathogenesis of the immunological disorders such as congenital immunodeficiency diseases and allergy was analyzed on the basis of the molecules concerning with the differentiation and function of lymphocytes. X-linked severe combined immunodeficiency is caused by the gene abnormality of cytokine receptor gamma-chain common for IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. WE analyzed the gene from Japanese patients and found some new mutations. T and NK cells are defective, while B cells are normally present in this disease. However, we found that immunoglobulin gene rearrangement in variable region of the patient B cells stays at immature stage and that these genes show few mutation which should be observed in mature B cells. These abnormalities were not corrected even after reconstitution of T cells by bone marrow transplantation, which indicated that these are caused by the defect of B cells themselves. X-linked hyper-IgM syndrome is the result of the gene abnormality of CD40 ligand.
… More
We analyzed the gene in 13 Japanese patients and found some new mutations. In one case 2 different mRNAs were transcribed from 1 abnormal gene. This was the first observation in this disease. Prenatal diagnosis by the gene analysis using amniotic cells was performed and the result was confirmed to be correct after birth, which shows that prenatal gene diagnosis is practically available in this disease. WASP gene abnormality causes Wiskott-Aldrich syndrome. Eight Japanese cases were analyzed for the gene and 3 new mutations were found. Aggregation of actin fibers in cytoplasma was found to be impaired in the cells transfected with mutant WASP gene, which indicated that WASP molecule is related to cell configuration. Mast cells bear Fcepsilon receptors and are triggered to release chemical mediators when IgE bound to the receptors reacts with antigen. We disclosed that transcription of Fcepsilon receptor gene is enhansed by IL-4. IL-4 also incleased anhesiveness of mast cells by integrin. These observations indicated that IL-r has a role acting on mast cells besides inducing IgE production. Less
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