Approarch for the viral agent responsible for rheumatoid arthritis

1.对6例类风湿关节炎患者滑膜组织中分离的人细小病毒B19（B19）进行了DNA序列分析。结果表明，与第五类疾病的B19 DNA相比，RA的B19 DNA中没有特异性区域。第五类疾病患者的抗B19抗体对B19感染的红系细胞中B19 DNA增加的抑制率在70%以上，而部分RA患者的抗B19抗体对B19 DNA增加的抑制率明显降低，提示RA患者可能允许B19在体内持续感染。我们发现了一种不同于红细胞P抗原的B19受体。B19感染T细胞后，T细胞趋化能力增强。4.建立了NS-1基因转染的巨噬细胞系U937-NS 1。加入IPTG后，TNFαmRNA和NS 1 mRNA的表达均增加，提示B19的NS 1可能参与了类风湿关节炎滑膜免疫细胞产生TNFα的过程。本研究旨在探讨NS 1基因激活诱导TNFα产生的分子机制。5.获得了NS 1转基因C57/B6（NS 1 Tg）小鼠。NS 1 Tg小鼠表现出II型胶原诱导的多关节炎的可行性。

1.We characterized DNA sequence of human parvovirus B19(B19) isolated from synovium tissues of 6 patients with rheumatoid arthritis. The results revealed no specific regions in B19 DNA derived from RA, compared with those from fifth desease.2.We evaluated neutralizing ability of B19 antibody in humans. Anti-B19 antibodies from patients with fifth disease showed above 70% of inhibition on the increase of B19 DNA in B19-infected erythroid cell lines, whereas some from RA had significantly decreased inhibition of B19 increase, indicating that RA patients might permit persistent B19 infection in vivo.3.B19 can proliferate not only in erythroid cells but also in immunocytes. We found a novel receptor for B19 which is different from P antigens in erythrocytes. The B19 infection to T cells caused an enhanced chomotaxic ability.4.We established NS-1-transfected macrophage cell line, U937-NS1. The addition of IPTG induced an enhanced production of TNFαmRNA and NS1 mRNA, indicating that NS1 of B19 may be responsible for the production of TNFα in immunocytes invading rheumatoid synovium. We are investigating precise mechanism of molecular mechanism of TNFα production evoked by the activation of NS1 gene.5.We obtained NS1 transgenic C57/B6(NS1Tg) mice. NS1 Tg mice showed a feasibility of type II collagen-induced polyarthritis.