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Mechanism for human parvovirus B19-induced rheumatoid arthjritis

人细小病毒B19诱导类风湿性关节炎的机制

基本信息

批准号：
16390284
负责人：
SASAKI Takeshi
金额：
$ 9.15万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390284/
关键词：
rheumatoid arthritis human parvovirus B19 KU80 neutralizing antibody siRNA ヒトパルボウィルスB19 TNFα ウイルス中和抗体 si RNA 持続感染レセプターマクロファージ T細胞 Ku80 P抗原低酸素

项目摘要

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.

1.临床研究：我们比较了类风湿关节炎（RA）患者在RA发病时是否有人类细小病毒B19 （B19）感染的临床特征。结果显示，B19患者的临床特征与不含B19.2的患者无差异。B19感染靶细胞的机制。B19作为靶细胞表面的细胞受体与Ku80和P抗原结合。B19通过claslin进入细胞。有人认为可能有一种未知的因素导致B19在细胞内转运到细胞核。类风湿关节炎中B19的中和抗体活性。中和抗体在B19感染的宿主防御中具有重要作用。我们研究了B19感染和类风湿关节炎患者抗B19的中和抗体活性。采用定量PCR法测定血清抗体对KU812Ep6红细胞B19感染的抑制作用。在大多数急性B19感染病例中，在症状消退时，中和能力水平升高。62例类风湿关节炎患者中有41例B19长期感染，尽管IgG抗B19抗体升高，但其中和能力仍明显较低。siRNA对B19增殖的抑制作用。B19 NS1的SiRNA抑制B19感染红细胞的增殖。在体外RA滑膜细胞原代培养体系中加入NS1 siRNA可显著抑制TNF α增殖，提示NS1 siRNA可能应用于RA的治疗。