摘要
目的检测再生障碍性贫血(AA)患者外周血CD4+CD25+Treg细胞和T细胞亚群的表达情况,分析两者与AA病情严重程度及免疫抑制剂疗效的关系,为评估AA患者病情、选择合理治疗方案提供依据。方法以46例接受免疫抑制剂(单用环孢素A)治疗的初诊AA患者和26例正常健康体检者为研究对象,采用多参数流式细胞术检测其细胞免疫功能,包括T细胞亚群、CD4+CD25+Treg细胞和效应性T细胞,按照正常对照组水平将患者分组:CD127low/CD127high比值正常型和降低型;CD4+/CD8+比值正常型、倒置型及正置型,分析比较各亚型与病情、疗效之间的关系,并进一步比较CD4+CD25+Treg细胞与T细胞亚群在评估AA患者免疫状态中的优劣。结果1CD127low/CD127high比值正常型占28.3%(13/46),降低型占71.7%(33/46);重型AA(SAA)与非重型AA(NSAA)两组降低型患者所占比例分别为89.5%(17/19)、59.3%(16/27),差异有统计学意义(χ2=5.022,P<0.05);单用环孢素治疗,总有效率为48.1%(13/27),有效者降低型比例92.3%(12/13),明显高于无效者降低型比例50.0%(7/14)(χ2=3.395,P<0.05)。2CD4+/CD8+比值正常型占39.1%(18/46),倒置型占39.1%(18/46),正置型占21.7%(10/46);SAA与NSAA两组中按CD4+/CD8+分型,两组间构成比例差异无统计学意义(χ2=0.211,P>0.05);单用环孢素治疗,有效和无效者按CD4+/CD8+分3种亚型,分别占有效者46.2%(6/13)、46.2%(6/13)、7.7%(1/13),无效者为35.7%(5/14)、28.6%(4/14)、35.7%(5/14),差异无统计学意义(χ2=2.983,P>0.05)。3CD4+CD25+Treg和T细胞亚群监测AA患者免疫状态异常的阳性率分别为71.7%(33/46)和60.9%(28/46),CD4+CD25+Treg监测免疫状态异常的敏感性高于T细胞亚群(χ2=4.290,P<0.05)。结论大多数患者存在CD4+CD25+Treg细胞和(或)T细胞亚群的异常,与AA发病机制的免疫异常密切相关;在监测AA患者免疫功能异常、评估病情及免疫抑制剂疗效时,CD4+CD25+Treg细胞比T细胞亚群更敏感;CD4+CD25+Treg细胞联合T细胞亚群的监测对临床了解AA病情和发病机制、合理用药、提高诊断和治疗水平有重要价值。
Objective To investigate the expression of regulatory T cells（Treg）and T-cell subgroups in patients with aplastic anemia （AA ） and the relationship between Treg and T-cell subgroups and the severity and immunosuppressive effect of AA,and to provide a basis for selecting rational therapy of AA patients.Methods Cellular immune function of 46 AA patients with immunotherapy were analyzed by tricolour fluorescence labeled monoclonal antibody and multiparameter flow cytometry,including T-cell subtypes,CD4^＋CD25^＋ Treg and effective T cells （Teff）.The AA patients were divided into normal type of ratio,inverted type of ratio,hypernormal type of ratio according to the ratio of CD4^ ＋/CD8^ ＋ cell in healthy control,and the AA patients were divided into normal type of ratio and low type of ratio according to the ratio of Treg/Teff cell in healthy control.Patients＇condition and therapeutic effects were investigated between subtypes in patients with AA.Results ① The percentage of the normal type and the low type of CD127 low/CD127 high in all patients was respectively 28.3% （13/46 ）and 71.1% （33/46 ）.There was significant difference in percentage of Treg/Teff low type between SAA and NSAA,89.5%（1 7/1 9）vs 59.3%（1 6/27） （χ^2 = 5.022, P 〈 0.05 ）. The total effective rate was 48.1% （13/27 ） treating AA patients with single immunosuppresive agent cyclosporine A （CsA）,and the rate of Treg/Teff low types of the effective patients was significantly higher than the ineffective patients 92.3% （12/13 ）vs 50.0% （7/14 ）,respectively （χ^2 = 6.677,P 〈0.01）.②According to the ratio of CD4^ ＋/CD8^ ＋ cells,the percentage of both normal type of ratio and inverted type of ratio in all patients was 39.1%（18/46）,the percentage of hypermormal type of ratio was 21.7%（10/46）.There was no significant difference on the percentage of CD4^ ＋/CD8^ ＋ types between SAA and NSAA（χ^2 = 0.21 1,P〉 0.05 ）. The rate of CD4^ ＋/CD8^ ＋ immunological subtypes treating only with CSA between SAA and NSAA was respectively 46.2%（6/13）,46.2%（6/13）,7.7%（1/13）and 35.7%（5/14）,28.6%（4/14）,35.7%（5/14）（χ2 =2.983,P〉0.05）.③The positive rates of CD4^＋CD25^＋ Treg cells and T cell subsets to monitor the abnormal immune status in patients with AA were 71.7% （33/46）and 60.9%（28/46）,respectively.The CD4＋ CD25 ＋ Treg to monitor abnormal immune status was significantly sensitive than that of T cell subsets （χ^2 =4.290,P 〈0.05）.Conclusion The abnormal ratios of CD4^＋CD25^＋ Treg and T-cell subgroups exist in the majority of AA patients,immunologic abnormality may play a role in pathogenesis of the patients with AA.The detection of CD4^＋CD25^＋ Treg in patients with AA was more sensitive than that T-cell subgroups,which may contribute to the evaluation of patients＇ condition and choice of rational treatment prescription.Detection of CD4^＋CD25^＋ Treg and T-cell subgroups may play an important role in evaluating the patients＇condition and pathogenesis,rational drug use,improving the diagnosis and treatment in patients with AA.
出处
《临床荟萃》
CAS
2015年第6期628-632,共5页
Clinical Focus
基金
安徽省科技攻关类战略新兴产业项目资助(11010402168)
