类风湿关节炎患者人类白细胞抗原-DR4/1表型与Ⅱ型胶原特异性T细胞增殖及血清Ⅱ型胶原抗体的关系

Relationship between HLA-DR4/1 subtypes and T cell responses to type Ⅱ collagen or anti-CⅡ263-272 antibodies

目的探讨类风湿关节炎(RA)患者HLA-DR4/1表型与Ⅱ型胶原(CⅡ)263-272多肽特异性T细胞增殖和血清CⅡ263-272抗体之间的关系。方法将CⅡ263-272多肽与70例RA患者外周血单个核细胞(PBMC)共孵育5天,用3H参入法测定T细胞增殖,用酶联免疫吸附测定法(ELISA)检测患者血清CⅡ263-272抗体水平。以序列特异性引物聚合酶链反应(PCR-SSP)技术对上述患者进行HLA-DR分型。结果在70例RA患者中,27例HLA-DR4/1表型阳性,43例HLA-DR4/1表型阴性。在HLA-DR4/1表型阳性的RA患者中,CⅡ263-272多肽可刺激T细胞增殖的有15例(55.6%),12例(44.4%)呈无反应性;18例(66.7%)患者抗CⅡ263-272抗体阳性。而在HLA-DR4/1表型阴性的RA患者中,T细胞对CⅡ263-272多肽有反应性者13例(30.3%),无反应性者30例(69.7%);15例(34.8%)RA患者抗CⅡ263-272抗体阳性。HLA-DR4/1表型阳性组CⅡ263-272特异性细胞增殖和CⅡ263-272抗体生成均高于HLA-DR4/1表型阴性组。结论RA患者CⅡ263-272特异性T细胞增殖和CⅡ263-272抗体生成与HLA-DR4/1表型有关。

Objective： To investigate the relationship between HLA-DR4/1 subtypes and T cell respon- ses to type Ⅱ collagen or anti-C Ⅱ 263-272 antibodies. Methods： Peripheral blood mononuclear cells and sera were obtained from 70 rheumatoid arthritis （RA） patients. T cell proliferative responses to C Ⅱ 263- 272 were evaluated by [^3H ] thymidine incorporation assay. Antibodies specific to C Ⅱ263-272 were determined by ELISA. HLA-DR4/1 subtypes were analyzed by PCR-SSP. Results： In HLA-DR4/1 positive group, T cell proliferative responses to C Ⅱ263-272 were observed in 55.6% RA patients and anti- C Ⅱ 263-272 antibodies were present in 66.7% RA patients. In HLA-DR4/1 negative group, T cell proliferative responses to C Ⅱ 263-272 were observed in 30.3% RA patients and anti-C Ⅱ 263-272 antibodies were present in 34.8% RA patients. The number of positive antibodies to C Ⅱ 263-272 or T cell prolifera- tive responses to C Ⅱ 263-272 in HLA-DR4/1 positive group were higher than in negative group. Conclusion： There is a relationship between HLA-DR4/1 subtypes and T cell responses to C 11263-272 or anti- C Ⅱ 263-272 antibodies.