HLA-DRB1*1501和TNF-α308位点基因多态性预测再生障碍性贫血免疫抑制疗法的疗效

目的 研究再生障碍性贫血(AA)患者HLA-DRB1*1501表型及肿瘤坏死因子-a（TNF-a） 308位点基因多态性对其免疫抑制疗法疗效的预测价值。方法 40例初治AA患者,给于环孢菌素（CsA）为主的免疫抑制治疗,应用PCR SSP方法分析HLA-DRB1*1501表型，用PCR-RFLP技术检测TNF-a308位点基因型,并随访评价上述各指标与患者预后的关系。结果 HLA-DRB1*1501表达阳性患者与阴性患者对免疫抑制治疗有效率分别为85.7%和46.2%（P=0.024）；TNF a308A（TNF2）阳性患者与阴性患者对免疫抑制治疗有效率分别是78.6%和48.1%（P=0.039）；HLA-DRB1*1501阳性TNF2阳性、HLA-DRB1*1501阳性TNF2阴性、HLA-DRB1*1501阴性TNF2阳性、HLA-DRB1*1501阴性TNF2阴性四种预测概率值分别为0.963、0.785、0.754、0.354。结论 HLA-DRB1*1501和TNF a联合检测有可能成为AA患者免疫抑制治疗疗效的预测方法。

Combined measurement of HLA-DRB1*1501 and the TNF-α-308 gene polymorphism in predicting response to immunosuppressive therapy for aplastic anemia

Objective    To investigate the correlation of the HLA-DRB1*1501 phenotype and TNF-a-308G/A gene polymorphism with response to immunosuppressive therapy for aplastic anemia(AA). Methods    Phenotypes of HLA-DRB1*1501 and polymorphisms of TNF-a-308 were respectively determined by PCR SSP and PCR-RFLP in 40 AA patients initially treated with immunosuppressive therapy based on cyclosporine (CsA).The relation between laboratory indexes and clinical response was investigated. Results    The response rates to immunosuppressive therapy of HLA-DRB1*1501+ and HLA-DRB1*1501 were 12/14(85.7%) vs 12/26(46.2%) (P=0.024), and of TNF-a-308A(TNF2)+and TNF2- were 11/14(78.6%) vs 13/27(48.1%)(P=0.039). Prediction probabilities of the four groups (HLA-DRB1*1501+TNF2+, HLA-DRB1*1501+TNF2 , HLA-DRB1*1501-TNF2+ and HLA DRB1*1501-TNF2) were 0.963, 0.785, 0.754 and 0.354 respectively.  Conclusion   The combined measurement of HLA-DRB1*1501  and TNF-a（308A）could be a predictor of response to immunosuppressive therapy for aplastic anemia and valuable for clinical application.