| Project/Area Number |
02670268
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Tokyo University |
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Principal Investigator |
TAKEUCHI Fujio Tokyo University.Medicine(Hospital) Fellow, 医学部(病), 助手 (70154979)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUNAGA Katsushi Tokyo University.Medicine(Hospital) Fellow, 医学部(病), 助手 (40163977)
NAKANO Keiichiro Tokyo University.Medicine(Hospital) Fellow, 医学部(病), 助手 (10090490)
MATSUTA Kunio Tokyo University.Medicine(Hospital) Lecture, 医学部(病), 講師 (80143436)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | arthritis rheumatism / HLA-DR / C4AQ0 / adenovirus / ethnics / auto-antibody / EB virus / susceptibility gene / C4AQO / 判別分析 / 日本と韓国 / エピトープ / HLAーDR / エピト-プ / 遺伝要因 / 補体第4成分 |
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| Research Abstract |
In this research program, genetical background of rheumatoid arthritis (RA) were studied on MHC class II and III, and pathogenesis of RA was discussed. It was confirmed that the sequence coding the amino acids QRRAA located at the position of 70 - 74 on HLA DRbeta chain, was most strongly associated with RA. The sequence is common among Dw15, DR1, Dw16, and is very closely similar to amino acid sequence of Dw4 and DR10 at the position. It indicated the possibility that the sequence was a susceptible sequence through ethnics. The sequence was also associated with Korean RA and a contribution of a sequence, QKRAA, to RA was also observed in Korea. Still more, whole conformation of HLA chain was also thought to be important. On the other hand C4AQ0 was associated with Japanese RA though the C4AQ0 did not have Caucasian-type deletion. C4AQ0 was not associated with QRRAA and any specific DR types. In Korea the slight increase of C4AQ0 was observed but not significant. The frequency of C4B5
… More
was increased and the association of C4B5 with Dw15 was observed in both Japanese and Korean. The C4AQ0 without Caucasian-type deletion was increased in both SLE and PSS. No patient with homozygote of C4AQ0 was deleted in this research series. The genetic factors did not affect on clinical features such as progression of the disease, positivity of rheumatoid factor and inflammation. These data suggested that patients would take almost similar clinical course even if their genetical backgrounds were different. But by the stastical method of Hayashi II, patients could be clasterized according to genetical parameters. For investigating the contribution of QRRAA to the pathogenesis of RA, homology search was carried out. Several agents were revealed to have the similar sequence. Among them, high titer of anti-EB virus antibody was observed in RA but it was not associated with the positivity of QRRAA and with clinical features. Antibody to adenovirus type V was not different between RA and normal control either. Auto-antibody against the synthetic peptide containing QRRAA was detected in RA and the positivity was high in RA patients with QRRAA. The auto-antibody was also observed in synovial fluid of RA patients but the pathogenic significance was unclear. Our data in the study make it clear that genetic factors play an important role in pathgenesis of RA. It would be important to study continuously the association of genetic factors with etiological mechanism of RA and environmental factors such as virus et al. in the future. Less
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