HIROHATA Shunsei University of Tokyo, Dep. of Medicine, Assistant Professor, 医学部(病)物療内科, 助手 (90189895)
木佐木 友成 東京大学, 医学部物療内科, 助手 (20169840)
SAWADA Tetsuji University of Tokyo, Dep. of Medicine, Assistant Professor, 医学部(病)物療内科, 助手 (50235470)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1991 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1990 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1989 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Synovial fluids(SF)and sera(S)from patients witn rheumatoid arthritis(RA)were examined for IgM, IgM-rheumatoid factor(IgM-RF). albumin in and interleukin-6(IL-6)activity. The quotient of SFIS IGN-RF was elevated compared with that of SF/S albumin in 7 patients with seropositiye RA, although the quotient of SF/S IgN was low er than that of SF/S albumin. SF IL-6 activity was much higher than serum IL-6 activity in all the 7 RA patients. In synovial fluids from 22 seropositiye RA patients, SF IL-6 activity was significantly correlated with the SF I gill-RF. IGG-RF and IGA-RF, but not with SF[gM, [gG or IgA. Moreover, SF IGM-RF as well as SF IL-6 activity was significantly correlated with the Westergren erythrocyte sedimentation rate(ESR)or the Lansbury articular index. These results indicate that(L-6and RF might be Produced within the rheumatoid joints as a result of abnormal im mune system activation, which is associated with the disease activity of RA. Three of the 4 seronegative RA pat
ients, however, showed high SF IL-6 without detectable levels of SF IGM-RF. indicating that IL-6 alone is not sufficient for IGM-RF production.
The expression of CD14, Fc gamma receptor l(FcgammaRI), FcrRH, and HLA-DR on peripheral blood monocutes from 9 atients with rheumatoid arthritis(RA)was studied to investigate their natures and their roles i. 1 the pathogenes is of rheumatoid synovitis. Peripheral blood mononuclear cells obtained from 9 patients with active RA, 8 patien ts with RA in complete remission, and 14 healthy individuals, were stained with various monoclonal antibodies and analyzed on fluourescence activated cell sorter. The expression of CD14 as well as FcgammaRI and FcgammaRII was upregu lated on peripheral blood monocutes from active RA patients, although the expression of HLA-DR was not increased. In addition, the expression of FcgammaRI and FcRII on monocutes was still upregulated in RA patients in complete remi ssion, whereas the expression of CD14 on sonocytes was normalized in these patients. These results indicate that Peripheral blood sonocytes in active RA patients are already activated to express higher densities of CD14. In ad dition, our observation that C014 density was increased on a subset of circulating blood monocutes in active RA, that HLA-DR was not significantly altered and that FcgammaRI and FcgammaRIl were increased in both active and inactive RA is not compatible with the expected actions of IFN-gamma. Finally, it is suggested that peripheral blood monocut es in RA patients may have intrinsic abnormalities as evidenced by the enhanced expression of FcgammaRs, which is pe rsistently observed irrespective of the disease activity of RA. The development of rheumatoid arthritis(RA)has been considered to involve both genetic and environmental f actors. We describe a patient who developed Progressive RA after transfusion-associated hepatitis C virus infect ion. Of interest, our patient possessed the combination of HLA-DR4 and HLA-Bw54, which has been frequently observe d in Japanese patients with RA, indicating that he was genetically susceptible to the disease. This suggests that hepatitis C virus may trigger the development of RA in genetically susceptible individuals. It should of course be pointed out that RA could have been a chance occurrence in our patient. Patients with RA and hepatitis C virus infection should be studied prospectively to seek evidence in the joint fluid, joint tissue, or elsewhere, to distinguish whether the RA is triggered by hepatitis C infection or whether hepatitis C virus itself resides in th e joint, causing either an immune complex reaction or direct cytotoxicity.