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

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5 d,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/I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/l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.

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

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 by3H]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-HA308-3 17 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.