益气养血方治疗再生障碍性贫血的免疫学指标与血常规变化规律探析

Changes of Immunological Indexes and Blood Routine in Treatment of Aplastic Anemia by Yiqi Yangxue Prescription

目的:探讨益气养血方联合西药治疗再生障碍性贫血(AA)血象升高患者的免疫学特征,以及免疫学指标对血象升高的预测作用,以期为疗效预测、治疗方案调整提供参考。方法:该研究为回顾性研究,选取2018年9月至2021年3月中国中医科学院西苑医院等19个分中心接受益气养血方联合西药治疗6个月的77例AA患者,按治疗6个月时血象恢复程度[包括血红蛋白(HGB)、白细胞计数(WBC)、血小板计数(PLT)及中性粒细胞计数(ANC)],将患者分为2组,一组血象较基线值增长<50%,另一组较基线值增长≥50%,比较两组的临床特征及免疫学特征。结果:①与HGB上升<50%组比较,HGB上升≥50%组患者治疗前CD3^(+)人白细胞DR抗原(HLA-DR)^(+)更高,且治疗前辅助型T细胞2(Th2)<5%、CD8^(+)≥50%及CD3^(+)HLA-DR^(+)≥9%的患者占比更高(P<0.05,P<0.01);多因素Logistic回归分析显示治疗前CD8^(+)≥50%是HGB升高≥50%的独立影响因素[比值比(OR)=12.000,95%置信区间(95%CI)2.218,64.928,P<0.01]。②与WBC上升<50%组比较,WBC上升≥50%组治疗前CD3^(+)HLA-DR^(+)<6%及T-box转录因子(T-bet)≥200%的患者占比更高(P<0.05);多因素Logistic回归分析显示治疗前CD3^(+)HLA-DR^(+)<6%(OR=2.998,95%CI 1.036,8.680,P<0.05)、T-bet≥200%(OR=3.634,95%CI 1.076,12.273,P<0.05)均是WBC升高≥50%的独立影响因素;③与PLT上升<50%组比较,PLT上升≥50%组治疗前Th1、CD3^(+)HLA-DR^(+)更低,且Th1<12%、CD4^(+)≥6%、CD3^(+)HLA-DR^(+)<5%的患者占比更高(P<0.05,P<0.01);多因素Logistic回归分析显示治疗前CD3^(+)HLA-DR^(+)<5%是PLT升高≥50%的独立影响因素(OR=16.190,95%CI 3.430,76.434,P<0.01)。④与ANC上升<50%组比较,ANC上升≥50%组治疗前各指标差异均无统计学意义。结论:益气养血方联合西药治疗在HGB增长快的AA患者中,表现出Th2<5%、CD3^(+)HLA-DR^(+)≥9%,CD8^(+)≥50%的AA 患者中更为显著;在WBC 增长快的AA 患者中,表现出CD3^(+)HLA-DR^(+)<6%和T-bet≥200%;在PLT 增长快的AA 患者中,表现出Th1<12%、CD4^(+)≥6%,尤其是CD3^(+)HLA-DR^(+)<5%的AA 患者中更为显著。

Objective:To investigate the immunological characteristics of the patients with aplastic anemia(AA)and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters,thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen.Method:A retrospective study was conducted,involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital,China Academy of Chinese Medical Sciences from September 2018 to March 2021.The patients were assigned into two groups according to the elevations in hemogram parameters[including hemoglobin(HGB),white blood cell count(WBC),platelet(PLT),and absolute neutrophil count(ANC)]after 6 months of treatment.One group had the elevation<50%,and the other group had the elevation≥50%compared with the baseline.The clinical and immunological characteristics were compared between the two groups.Result:①Compared with the group with HGB elevation<50%,the group with HGB elevation≥50%showed elevated level of CD3^(+)human leukocyte antigen-DR(HLA-DR)^(+)and increased proportion of patients with T-helper cell type 2(Th2)<5%,CD8^(+)≥50%,and CD3^(+)HLA-DR^(+)≥9%before treatment(P<0.05,P<0.01).The multivariate Logistic regression analysis showed that CD8^(+)≥50%before treatment was the independent influencing factor for HGB elevation≥50%[odds ratio(OR)=12.000,95%confidence interval(CI)2.218,64.928,P<0.01].②Compared with the group with WBC elevation<50%,the group with WBC elevation≥50%showed increased proportion of patients with CD3^(+)HLA-DR^(+)<6%and T-box transcription factor(T-bet)≥200%before treatment(P<0.05).The multivariate Logistic regression analysis showed that CD3^(+)HLA-DR^(+)<6%(OR=2.998,95%CI 1.036,8.680,P<0.05)and T-bet≥200%(OR=3.634,95%CI 1.076,12.273,P<0.05)before treatment were independent influencing factors for WBC elevation≥50%.③Compared with the group with PLT elevation<50%,the group with PLT elevation≥50%presented lowered Th1 and CD3^(+)HLA-DR^(+)levels and increased proportion of patients with Th1<12%,CD4^(+)≥6%,and CD3^(+)HLADR^(+)<5%before treatment(P<0.05,P<0.01).The multivariate Logistic regression analysis showed that CD3^(+)HLA-DR^(+)<5%before treatment was the independent influencing factor for PLT elevation≥50%(OR=16.190,95%CI of 3.430 to 76.434,P<0.01).④Compared with the group with ANC elevation<50%,the group with ANC elevation≥50%showed no significant changes in the hemogram parameters before treatment.Conclusion:As for the AA patients with rapid elevation in HGB,Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5%and CD3^(+)HLA-DR^(+)≥9%,especially those with CD8^(+)≥50%.As for the AA patients with rapid elevation in WBC,the therapy was particularly effective in the patients with CD3^(+)HLA-DR^(+)<6%and T-bet≥200%.As for the AA patients with rapid growth in PLT,the therapy was particularly effective in the patients with Th1<12%and CD4^(+)≥6%,especially those with CD3^(+)HLA-DR^(+)<5%.