干扰素γ联合HLA-DRB1*1501预测再生障碍性贫血免疫抑制疗法的应用价值  

Clinical implications of combined measurement bone marrow T cells intracellular IFNγ and HLADRB1*1501 measurement in predicting the response to immunosuppressive therapy for aplastic anemia

作　　者：陈昀[1] 徐从高[2] 郭农建[3] 黄平[3] 肖东杰[3] 丁卜同[3] 葛林阜[4] 

机构地区：[1]山东大学医学院临床学院,济南250012 [2]山东大学齐鲁医院血液科 [3]济南市中心医院 [4]济南军区总医院

出　　处：《中华内科杂志》2007年第10期846-849,共4页Chinese Journal of Internal Medicine

基　　金：山东省自然科学基金(Y2002C07)

摘　　要：目的研究和评价骨髓 T 淋巴细胞内 IFNγ与 HLA-DRB1*1501联合检测在再生障碍性贫血(AA)免疫抑制疗法(IST)疗效预测中的临床应用价值。方法 51例以含环孢素 A 的 IST 治疗的 AA 患者,治疗前检测骨髓 CD_8^+ T 细胞内 IFNγ染色和 HLA-DRB1*1501,随访后评价上述指标与临床疗效的关系。结果细胞内 IFNγ阳性的灵敏度为94.3%(33/35),特异度为62.5%(10/16);HLA-DRB1*1501阳性的灵敏度为45.7%(16/35),特异度为87.5%(14/16)。两者联合后,并行试验灵敏度和阴性预测值提高(分别为97.1%和90.0%);串联试验特异度和阳性预测值升高(均为93.7%)。由 logistic 回归方程计算出双阳性、细胞内 IFNγ阳性伴 HLA-DRB1*1501阴性、细胞内IFNγ阴性伴 HLA-DRB1*1501阳性和双阴性4组患者的预测概率分别为89.0%、77.4%、34.5%、18.2%。结论骨髓 T 细胞内 IFNγ和 HLA-DRB1*1501表型均简便实用,两者联合可以作为具临床实用价值的一种预测 AA 患者 IST 疗效的方法,双阳性预示患者治疗有效的可能性更高,对于大多数细胞内 IFNγ阳性的原发性 AA 患者来说有重要意义。Objective To evaluate the clinical implication of combined measurement of bone marrow （BM） T lymphocyte intracellular IFNγ with HLA-DRB1 ＊ 1501 in predicting the response to immunosuppressive therapy （IST） in patients with aplastic anemia （AA）. Methods Enrolled into the present study were 51 idiopathic AA patients treated with cyclosporine A （CsA） based IST. BM CD8^＋ T lymphocyte intracellular IFNγ was determined with flow cytometry and HLA-DRB1 ＊ 1501 detected with PCR- sequence specific primer before treatment. The relationship between laboratory indices and clinical response were investigated and the potential usefulness of parameters in predicting the response to IST for AA was evaluated. Results These HLA-DRB1 ＊ 1501 shows sensitivity of 45.7% （ 16/35 ） and specificify of 87. 5% （14/16） respectively. Intracellular IFNγ has sensitivity of 94. 3% （33/35） and specificity of 62.5% （10/16）, respectively. With combination of intracellular IFNγ with HLA-DRB1 ＊ 1501, the parallel test increases the sensitivity of 97. 1% （54/35） and the negative predictive value of 90.0% （9/10）. On the other hand, the serial test improves the specificity and positive predictive value which both achieve 93.7% （15/16）. It could be calculated through a logistic regression equation that the probabilities of prediction of four subgroups of patients whose results are both positive reaction, a positive intracellular IFNγ plus negative HLA-DRB1 ＊ 1501, a negative intracellular IFNγ plus positive HLA-DRB1 ＊ 1501 and both negative reaction are 89.0% , 77.4%, 34. 5% and 18.2% , respectively. Conclusions Combination of BM T ceils intracellular IFNγ stain and HLA-DRB1 ＊ 1501 phenotype can be a useful predictor for AA patients in immunosuppressive therapy. The patients with both positive results of the two tests may have more possibilities to response to IST. It may have an important implication for the majority of AA patients whose intracellular IFNγ stain has a positive reaction

关 键 词：贫血 再生障碍性 干扰素Ⅱ型 免疫抑制剂 HLA-DR抗原 

分 类 号：R556[医药卫生—血液循环系统疾病]