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

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

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。

Objective To investigate the correlation of the HLA-DRB1＊ 1501 phenotype and the 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.