Mechanism for human parvovirus B19-induced rheumatoid arthjritis

1.临床研究：比较类风湿关节炎(RA)患者发病时有无人类细小病毒B19(B19)感染的临床特征。B19感染靶细胞的机制：B19与Ku80结合，P抗原作为靶细胞表面的细胞受体。B19进入细胞是通过claslin实现的。提示B19的胞内转运可能存在未知因素。3.中和抗体在类风湿关节炎中的活性。中和抗体在B19感染的宿主防御中起重要作用。我们研究了B19感染和类风湿关节炎患者中抗B19的中和抗体活性。用定量聚合酶链式反应检测血清抗体对红系细胞株KU812EP6中B19感染的抑制作用。在大多数急性B19感染病例中，症状缓解时中和能力水平升高。在62例类风湿关节炎患者中，有41例持续感染B19的患者的中和能力仍明显低下。4.针对B19的siRNA抑制B19的增殖。在RA滑膜细胞原代培养体系中加入NS1siRNA可明显抑制肿瘤坏死因子α的增殖，提示NS1siRNA有可能应用于RA的治疗。

1.Clinical study:We compared clinical features of patients with rheumatoid arthritis(RA) who had or had not the evidences of human parvovirus B19 (B19) infection at the onset of RA. The result revealed no differences between the clinical profile of patients with B19 and that without B19.2.Mechanism for the B19 infection to the targeted cells.B19 bound to Ku80 and P antigen as the cellular receptor on on the surface of targeted cells. The entry of B19 into cells occurred using claslin. It has been suggested that there may be an unknown factor that is responsible for the intracellular transportation of B19 to nucleus.3.Neutralizing antibody activity to B19 in rheumatoid arthritis.Neutralizing antibodies has an important role on the host defence at B19 infection. We studied neutralizing antibody activity against B19 in patients with B19 infection and rheumatoid arthritis. The neutralizing activity was ddetermined through the ability of serum antibody to inhibit B19 infection in erythroid cell line KU812Ep6 using quantitative PCR assay. The levels of neutralizing ability elevated at symptomatic resolution in most cases with acute B19 infection. Despite the elevation of IgG anti-B19 antibodies, the neutralizing ability remained markedly low in patients with prolonged B19 infection in 41 of 62 patients with rheumatoid arthritis.4.Inhibition of B19 proliferation by siRNA against B19.SiRNA to B19 NS1 inhibited B19 proliferation in B19-infected erythroid cell lines. The addition of NS1 siRNA to primary culture system using RA synovial cells in vitro caused marked inhibition of TNF α proliferation, indicating a possible application of NS1 siRNA to the therapy for RA.