类风湿关节炎患者HLA—DR4／1表型与流感病毒血凝素特异性T细胞增殖及其抗体的关系

Relationship between HLA-DR4/1 subtypes and T cell response to influenza virus hemagglutinin or anti-HA308-317 antibodies in rheumatoid arthritis

目的探讨类风湿关节炎（RA）患者人类白细胞抗原（HLA）-DR4／1表型与流感病毒血凝素（HA）308-317多肽特异性T细胞增殖和血清抗HA308-317抗体之间的关系。方法将HA308-317多肽与70例RA患者外周血单个核细胞（PBMC）共孵育5d，^3H掺入法测定T细胞增殖。用ELISA法检测RA患者血清HA308-317抗体水平。以序列特异性引物聚合酶链反应（PCR-SSP）技术对RA患者进行HLA-DR分型。结果在70例RA患者中，27例HLA-DR4／1表型阳性。其中，HA308-317多肽可刺激T细胞增殖的RA患者有17例（62.9％），10例无反应性；15例（55．6％）HLA-DR4／阳性RA患者抗HA308-317抗体阳性。在HLA-DR4／1表型阴性的RA患者中，T细胞对HA308-317多肽有反应性者10例（23．3％），无反应性者33例；25例（58．1％）患者抗HA308-317抗体阳性。HLA-DR4／1表型阳性组HA308-317特异性细胞增殖高于HLA-DR4／1表型阴性组（P〈0．01），但两组血清中HA308—317抗体水平差异无统计学意义（P〉0．05）。结论RA患者HA308-317特异性T细胞增殖与HLA-DR4／1表型有关，HA308-317抗体生成与HLA-DR4／1亚型无明显关系；HA308—317多肽可能通过诱导HLA-DR4／1特异性T细胞活化参与RA的发病。

Objective To investigate the relationship between HLA-DR4/1 subtypes and T cell response to influenza virus hemagglutinin （HA） as well as anti-HA308-317 antibodies in rheumatoid arthritis （RA）. Methods The peripheral blood mononuclear cells （PBMCs） from 70 RA patients were cultured with HA308-317 for 5 days. T cell proliferative responses to HA308-317 were evaluated by [^3H] thymidine incorporation assay. ELISA was used to detect the antibodies to HA308-317. HLA-DR4/1 subtypes were analyzed by PCR with sequence-specific primers. Results Twenty-seven of the 70 RA patients （38.6%） were positive for HLA-DR4/1 subtypes and 43 patients （61.4%） were negative for HLA-DR4/1 subtypes. In the HLA-DR4/1 positive group, T cell proliferative response to HA308-317 was observed in 17 （62.9%） RA patients and anti-HA308-317 antibodies were present in 15 RA patients （55. 6% ）. In the HLA-DR4/1 negative group, T cell proliferative response to HA308-317 was observed in 10 （23.3%） patients and anti- HA308-317 antibodies were present in 25 （58.1%） patients. T cell proliferative response to HA308-317 in the HLA-DR4/1 positive group was higher than in the negative group （P 〈 0. 01 ）. However, there was no significant difference in production of antibodies to HA308-317 between the HLA-DR4/1 positive and negative groups （ P 〉 0. 05）. Conclusion There is a relationship between HLA-DR4/1 subtypes and T cell response to HA308-317. Antibodies to HA308-317 are not associated with HLA-DR4/1 phenotype. HA308- 317 peptide may be involved in the pathogenesis of RA through activating HLA-DR4/1 specific T cells.