1997 Fiscal Year Final Research Report Summary
Molecular cloning of autoantigens in rheumatoid arthritis
| Project/Area Number |
08457152
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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 |
内科学一般
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
OZAKI Shoichi KYOTO UNIVERSITY,Graduate School of Medicine Associate Professor, 医学研究科, 講師 (00231233)
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| Co-Investigator(Kenkyū-buntansha) |
HOSODA Kiminori KYOTO UNIVERSITY,Graduate School of Human and Environmental Studies Assistant Pr, 人間環境学研究科, 助手 (40271598)
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| Project Period (FY) |
1996 – 1997
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| Keywords | rheumatoid arthritis / synovial cells / synovial fluid / IgG / cDNA / expression cloning / follistatin-related protein / molecular biology |
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| Research Abstract |
We cloned three cDNAs encoding autoantigens in rheumatoid arthritis (RA) by immunological screening of lambda phage synovial cell-cDNA libraries with synovial fluid IgG, both of which were derived from RA patients. One of the isolated cDNA clones was found to encode follistatin-related protein (FRP).
ERP was first cloned as a transforming growth factor (TGF) beta1-inducible protein encoded by the TSC36 gene from a mouse osteoblastic cell line, and later human and rat homologues were cloned from glioma cell lines and named due to their similarity at the amino acid sequence level to follistatin (an inhibitor of activin), termed an FS module. FRP is a secreted extracellular soluble protein with unknown function. Immunoblotting analyzes detected serum antibodies to E.coli-expressed recombinant FRP in RA patients at a frequency of 30% (n=67), which was higher than those observed in any other systemic rheumatic diseases ; 10% (n=51) in systemic lupus erythematosus (P<0.01), 17% (n=18) in systemic sclerosis, 10% (n=10) in Sjogren's syndrome, and 0% (n=13) in polymyositis/dermatomyositis (P<0.05). Most of the epitopes were found within the EC domain. T cell antigenicity of FRP in RA patients remains to be examined. As follistatin specifically inhibits activin, FRP might inhibit or alter the growth factor-like activities of as yet unidentified ligands such as activin. It is therefore possible that antibodies to secreted soluble FRP might modify its function in the extracellular environment to exert some effect on the pathogenic process of RA.
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