Project/Area Number |
13670441
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
内科学一般
|
Research Institution | HOKKAIDO UNIVERSITY |
Principal Investigator |
KOBAYASHI Seiichi Hokkaido Univ., Coll. Of Med. Tech., Prof., 医療技術短期大学部, 教授 (30150246)
|
Co-Investigator(Kenkyū-buntansha) |
MORIYAMA Takanori Hokkaido Univ. Coll. Of Med. Tech., Asso. Prof., 医療技術短期大学部, 助教授 (20312423)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | systemic lupus erythematosus / RT-PCR / BAFF / BCMA / TACI / BAFF-R / anti-DNA antibody / alternative splicing / モノクローナル抗体 / ELISA / 生物製剤 / B細胞活性化 / TNFファミリー |
Research Abstract |
1. Although it was reported that serum levels of BAFF were elevated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), we found no difference of BAFF gene expression by BPMC between healthy donors and SLE patients. 2. Gene expression of three receptors for BAFF, i.e., BCMA, TACI and BAFF-R, by PBMC from SLE patients was upregulated in most cases and upregulation of BAFF-R gene expression was likely involved in anti-DNA autoantibody production. 3. We tried to establish monoclonal antibodies against BAFF, TACI or BCMA, but this project has not yet succeeded. 4. We cloned a TACI mRNA variant, which was possibly generated by alternative splicing (exon skipping) of the exon(s) encoding the extracellular domain. Defect of 46 amino acids and one amino acid substitution in extracellular region, and intact transmembrane and intracellular region were presumed in this splice variant, compared with full-length TACI mRNA. Expression and function of this variant protein are now under investigation.
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