| Project/Area Number |
16591020
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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 | GIFU UNIVERSITY |
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Principal Investigator |
KANEKO Hideo Gifu University, University hospital, Assistant Professor, 医学部附属病院, 講師 (80293554)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAO Toshiyuki Gifu University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70260578)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | primary immunodeficiency / IgA deficiency / CVID / IgA subclass / TACI / alpha germline transcript / Bloom症候群 / BLM / common mutataion / Hyper IgM免疫不全症 / AID |
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| Research Abstract |
Selective IgA deficiency and common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency, the molecular basis of which is unknown. To investigate the cause of selective IgA deficiency, we examined what stage of B-cell differentiation was blocked. DNA and RNA were extracted from three Japanese patients with selective IgA deficiency and three with a partial IgA deficiency. In selective IgA deficiency patients, I alpha germline transcript expression levels decreased and alpha circle transcripts were not detected. Stimulation with PMA and TGF-beta1 up-regulated I alpha germline and alpha circle transcripts. In some patients, IgA secretion was induced by stimulation with anti-CD40, IL-4 and IL-10. In partial IgA deficiency patients, I alpha germline, alpha circle transcripts and C alpha mature transcripts were detected in the absence of stimulation. Our findings suggest that the decreased expression level of I alpha germline transcripts before a class switch might be critical for the pathogenesis of some patients with selective IgA deficiency. However, in patients with a partial IgA deficiency, B-cell differentiation might be disturbed after a class switch.
In addition we established the assay system, which could detect the expression of IgA1 and IgA2 gene specifically. This assay system is useful for elucidating the pathogenesis of CVID and IgA deficiency.
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