2005 Fiscal Year Final Research Report Summary
Functional analysis of APRIL and BAFF, and the study of their role in the pathogenesis of autoimmune disease
| Project/Area Number |
16590984
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
TSUKAMOTO Hiroshi Kyushu University, University Hospital, Research Asociate, 大学病院, 助手 (70304772)
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| Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Takehiko Kyushu University, University Hospital, Assistant Professor, 大学病院, 講師 (90219212)
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| Project Period (FY) |
2004 – 2005
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| Keywords | APRIL / BAFF / BR3 / B cell / SLE / susceptible gene / polymorphism / TNF family |
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| Research Abstract |
Objective. To investigate the role of APRIL and BAFF, new members of the TNF family, in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
Results. By exon-specific PCR/SSCP, we identified two novel polymorphisms at codon 67 and 96 in APRIL gene. Both had amino acid substitutions, G67R and N96S, respectively. Only the 67G allele was associated with SLE in 148 Japanese SLE patients with allele frequency 0.662 compared with 0.575 for 146 healthy controls (p=0.0302). The frequency of the individuals who possessed at least one 67G allele in SLE patients (91.9%) was significantly higher than that in normal controls (80.1%) (p=0.0036). We developed ELISA for APRIL and BAFF, and demonstrated that serum levels of APRIL and BAFF were elevated in patients with SLE compared with healthy controls. We also identified a novel polymorphism, P21R, in BR3 gene. P21R is located in the cystein-rich domain of BR3, a specific receptor for BAFF, and could be functionally important. To investigate the reverse-signal through membrane BAFF, we constructed cDNA for membrane BAFF, which was not cleaved by furin convertase, by site-directed mutagenesis.
Conclusion. These results suggest that the 67G allele of APRIL is a contributing factor in the pathogenesis of SLE. The elevated serum levels of APRIL and BAFF may be associated with the pathogenesis of SLE. APRIL and BAFF could be a therapeutic target in the treatment of autoimmune disease.
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[Journal Article] A Phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease.2006
Author(s)
Tsukamoto H, Nagafuji K, Horiuchi T, Miyamoto T, Aoki K, Takase K, Henzan H, Himeji D, Koyama T, Miyake K, Inoue Y, Nakashima H, Otsuka T, Tanaka Y, Nagasawa K, Harada M
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Journal Title
Ann Rheum Dis 65
Pages: 508-514
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular Analysis of A Novel Hereditary C3 Deficiency with Systemic Lupus Erythematosus.2005
Author(s)
Tsukamoto H, Horiuchi T, Kokuba H, Nagae S, Nishizaka H, Sawabe T, Harashima S, Himeji D, Koyama T, Otsuka J, Mitoma H, Kimoto Y, Hashimura C, Kitano E, Kitamura H, Furue H, Harada M
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Journal Title
Biochem.Biophys.Res.Commun 330
Pages: 298-304
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT.2005
Author(s)
Horiuchi T, Gondo H, Miyagawa H, Otsuka J, Inaba S, Nagafuji K, Takase K, Tsukamoto H, Koyama T, Mitoma H, Tamimoto Y, Miyagi Y, Tahira T, Hayashi K, Hashimura C, Okamura S, Harada M
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Journal Title
Genes Immun 6
Pages: 162-166
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel mutations in TNFRSF1A in patients with typical tumor necrosis factor receptor-associated periodic syndrome and with systemic lupus erythematosus in Japanese.2004
Author(s)
Horiuchi T, Tsukamoto H, Mitoma H, Miyagawa H, Tamimoto Y, Yoshizawa S, Harada M, Hayashi K, Hashimura C, Oribe M, Okamura S
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Journal Title
Int J Mol Med 14
Pages: 813-818
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association of a four-amino acid residue insertion polymorphism of the HS1 gene with systemic lupus erythematosus : molecular and functional analysis.2004
Author(s)
Otsuka J, Horiuchi T, Yoshizawa S, Tsukamoto H, Sawabe T, Kikuchi Y, Himeji D, Koyama T, Mitoma H, Watanabe T, Harada M
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Journal Title
Arthritis Rheum 50
Pages: 871-881
Description
「研究成果報告書概要(欧文)」より
