2004 Fiscal Year Final Research Report Summary
Studies of B cell development defects inpatients with a gamma globulinemia
| Project/Area Number |
15591095
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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 | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
KANEGANE Hirokazu Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Pediatrics, Assistant Professor, 附属病院, 講師 (00293324)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Agammaglobulinemia / Bone marrow / B cells / Pre B cells / Pro B cells / Flow cytometry / X-linked agammaglobulinemia / Bruton's tyrosine kinase |
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| Research Abstract |
We investigated many patients with primary immunodeficiencies from Japan and other countries by flow cytometric and genetic analyses. X-linked agammagbbulinemia (XLA) fundamentally occurs in male, havever, a female carrier of XLA present agammagbbullnemia by extremely skewed X-chromosome in activation, who is the fist case all over the world. We performed genetic analysis of Korean patients with severe combined immunodeficiencies, and identified the fist case of IL-7 receptor-α and γc deficiency in Korea. We studied the clinical diagnosis of Japanese patients with XLA, and demonstrated that some patients showed atypical phenotypes.
Approximately 90% of male patients with B cell deficient agammaglobulinemia are XLA, and the remaining 10% of those may have autosomal recessive trait. It was described that μ heavy chain, λ5, Igα, and BLNK genes were responsible for autosomal recessive agammaglobulinemia, but the mutation in these genes have not been identified in Japan. Analysis of the bone marrow showed that the maturation arrest from pro B cells into pie B-1a cells was observed in XLA patients, and we investigated the bone marrow B cells in non-XLA patients. Some patients demonstrated the maturation arrest from pro B cells into pre B-1a cells as shown in XLA patient, and others showed the maturation stop before pro B cells. One patient demonstrated that the maturation arrest from pre B1-b cells into pre B2 cells, and this profile was similar with that observed in Igα knockout mice. We investigated Igα gene in the patient, but could not identify the mutation. B cell maturation arrests may occur at various stages in agammaglobulinemia, and we would study the bone marrow B cells in more patients with non-XLA in the future.
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