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The role of rheumatoid factor on altered immune responses of intra-articular lymhocytes in rheumatoid arthritis.

类风湿因子对类风湿性关节炎关节内淋巴细胞免疫反应改变的作用。

基本信息

批准号：
01570354
负责人：
INOUE Tetsufumi
金额：
$ 1.34万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

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 … More 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. Less

对类风湿关节炎(RA)患者的滑液(SF)和血清(S)进行了IgM、IgM-类风湿因子(IgM-RF)检测。白蛋白和白介素6活性。7例血清阳性RA患者SFISIGN-RF的商数高于SF/S白蛋白的商数，但SF/S白蛋白的商数低于SF/S白蛋白的商数。7例RA患者sF IL-6活性均显著高于血清IL-6活性。在22例血清阳性RA患者的滑液中，SF IL-6活性与SF I-Gill-RF显著相关。Ig G-RF和IGA-RF，但不与SF[GM，[GG或IgA].此外，SF-IGM-RF和SF IL-6活性与Westgren血沉(ESR)或Lansbury关节指数显著相关。提示类风湿关节内可能存在免疫系统异常激活而产生L-6和类风湿因子，与类风湿关节炎的疾病活动性有关。4例血清阴性RA中的3例PAT…然而，更多的文献显示高水平的sFIL-6，而没有检测到sFIGM-RF的水平。对9例类风湿关节炎(RA)患者外周血中CD14、Fcγ受体L(FcGammaRI)、FcrRH和HLADR的表达进行了研究，以探讨它们的性质及其作用：1类风湿滑膜炎。对9例活动期RA患者、8例RA完全缓解期患者和14例健康人的外周血单个核细胞进行各种单抗染色，并用荧光活化细胞分选仪进行分析。活动期RA患者外周血单核细胞CD14、FcGammaRI和FcGammaRII表达上调，而HLADR表达无明显变化。此外，完全缓解期RA患者单核细胞表面FcGammaRI和FcRII的表达仍然上调，而CD14的表达在这些患者中正常。这些结果表明活动期RA患者的外周血声母细胞已经被激活以表达更高密度的CD14。此外，我们观察到活动期RA患者外周血单核细胞C014密度升高，人类白细胞抗原-DR无明显改变，而活动期和非活动期RA患者FcGammaRI和FcGammaRIl均升高，与干扰素-γ的预期作用不相容。提示RA患者外周血单核细胞可能存在内源性异常，表现为FcGammaRs表达增强，这种异常与RA的病情活动无关。类风湿关节炎(RA)的发展被认为与遗传和环境因素有关。我们描述了一例输血相关丙型肝炎病毒感染后发展为进行性类风湿性关节炎的患者。有趣的是，我们的患者具有人类白细胞抗原-DR4和人类白细胞抗原-Bw54的组合，这在日本的类风湿关节炎患者中经常观察到，这表明他在遗传上对这种疾病易感。这表明丙型肝炎病毒可能在遗传易感个体中触发类风湿性关节炎的发展。当然，应该指出的是，类风湿性关节炎可能是我们患者的偶然事件。应对RA和丙型肝炎病毒感染的患者进行前瞻性研究，在关节液、关节组织或其他地方寻找证据，以区分RA是由丙型肝炎感染引发的，还是丙型肝炎病毒本身存在于关节内，引起免疫复合体反应或直接细胞毒性。较少