多变量模型预测再生障碍性贫血免疫抑制疗法疗效的初步研究  

Preliminary study of multivariable model in predicting response to immunosuppressive therapy in patients with 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] 余喆[4] 常亚丽[3] 周亚伟[3] 

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

出　　处：《中华血液学杂志》2007年第9期583-586,共4页Chinese Journal of Hematology

基　　金：山东省自然科学基金(Y2002C07)

摘　　要：目的研究和评价外周血 T 细胞亚群、骨髓 T 淋巴细胞内 IFN-γ表达、Th_1/Th_2及 Tc_1/Tc_2值及 HLA-DRB1*1501表型在再生障碍性贫血(AA)患者免疫抑制疗法(IST)疗效预测中的价值;探讨建立临床和实验室指标多变量 AA 患者 IST 疗效预测模型的可行性。方法采用流式细胞术检测51例 AA 患者治疗前后外周血 T 细胞亚群,骨髓 T 细胞 IFN-γ、IL-4、并分析上述指标与疗效的关系。结果在所评价的指标中,CD8^+细胞内 IFN-γ的预测值最高,其灵敏度和特异度分别为94.3%和62.5%,阳性和阴性预测值分别为84.6%和83.3%,细胞内 IFN-γ阳性且 Tc_1/Tc_2<50能提高阳性预测值达92.3%。以中性粒细胞绝对计数(ANC)、骨髓 T 细胞内 IFN-γ染色、Tc_1/Tc_2分层和 HLA-DRB1*1501表型4个指标建立一个多变量模型,可用于诊断点的确定和个体患者治疗有效概率的预测。结论骨髓 CD8^+T 细胞内 IFN-γ敏感性和特异性最好,但对细胞内 IFN-γ阳性的原发性 AA 患者预测价值受限;CD8^+细胞内 IFN-γ阳性且 Tc_1/Tc_2<50预示患者有更多的机会通过 IST 治疗获得缓解;提示多变量 AA 患者 IST 疗效预测模型较单一预测指标更加适合临床,具有潜在的临床应用价值。Objective To evaluate the potential usefulness of a muhivariable model in predicting the response to immunosuppressive therapy （IST） in patients with aplastic anemia （AA）, and its application to the clinical practice. Methods PB T cells subpopulation and BM T cells intracellular IFN-γ and IL-4 were serially analyzed by flow cytometry （FCM） before and during treatment. HLA-DRB1 ＊ 1501 phenotype was analyzed by PCR-SSP. The predictive potentials of different parameter combinations for clinical responsiveness were statistically assessed. Results In all evaluated parameters, CD8^＋ cell intracellular IFN-γ had the relatively best diagnostic value with sensitivity and specificity of 94.3% and 62.5%, and positive and negative predictive value of 84.6% and 83.3% respectively. Positive CD8^＋ cell intracellular IFN-γ plus Tc1/Tc2 〈 50 could increase the positive predictive value to 92.3%. A muhivariable model consisting of absolute neutrophil count （ANC）, BM T cell intracellular IFN-γ, Tc1/Tc2 ratio and HLA-DRB ＊ 1501 phenotype of the patients was finally established. Conclusion The muhivariable model is superior to each of the single parameters in terms of predictive power of IST therapeutic outcome, and its higher accuracy and the clinical application make it potentially useful in practice.

关 键 词：贫血 再生障碍性 细胞因子 HLA表型 免疫抑制剂 疗效 

分 类 号：R556[医药卫生—血液循环系统疾病]