T辅助细胞极化群体在儿童慢性特发性血小板减少性紫癜发病机制中的作用研究

Study on T helper cell polarized populations in children with chronic idiopathic thrombocytopenic purpura

目的探讨儿童慢性特发性血小板减少性紫癜(CITP)发病中,T辅助细胞(Th)亚群细胞因子的变化。方法采用定量夹心酶联免疫测定技术检测30例CITP患儿疾病活动期及治疗达完全缓解后,血清中Th1细胞因子白细胞介素(IL)-2、干扰素(IFN)-γ,Th2细胞因子IL-4,IL-5,IL-10和Th3细胞因子转化生长因子(TGF)-β1的变化。结果1在疾病活动期,Th1型细胞因子IL-2和IFN-γ浓度较正常对照组儿童显著升高,差异有显著意义(P<0.01);Th2型细胞因子IL-4,IL-5和IL-10浓度较正常对照组儿童降低,其中IL-4和IL-10显著低于对照组(P<0.01);Th1/Th2,(IL-2+IFN-γ)/(IL-4+IL-5)明显高于对照组(P<0.01),并且与患儿外周血小板计数呈负相关(RR=0.2515,P=0.0174);血清TGF-β1较对照组减少(P<0.01)。2治疗缓解期,血清中Th2型细胞因子较疾病活动期明显升高,Th1/Th2明显下降,差异有显著意义(P<0.01),血清TGF-β1明显增加,显著高于疾病活动期(P<0.01)。结论CITP患儿存在异常的淋巴细胞极化状态,是一种Th1类优势疾病。疾病活动期,患儿具有Th1细胞因子活动模式,在疾病缓解期,Th1向Th2模式迁移,血清TGF-β1明显增加,Th3与Th2细胞协同发挥负性免疫调节作用,血小板逐渐上升。控制CITP中细胞因子反应,可能是免疫治疗的一种有效方式。

Objective To investigate the roles of T helper cell （Th） polarized populations in the pathogenesis of chronic idiopathic thromboeytopenic purpura （CITP） in children. Methods The serum levels of Thl type cytokines IL-2,IFN-γ,Th2 type cytokines IL-4,IL-5,1L-10 and Th3 type cytokines transforming growth factor -betal （TGF-β1） in 30 children with CITP were measured by using quantitative sandwich enzyme /mmunoassay technique in the stage of attack and remission respectively. Results The results showed that： ① In the period of onset ,IL-2 and IFN-γ were significantly increased in children with CITP than in healthy controls （P〈0. 01）. By contrast, the serum levels of IL-4,1L-5 and IL-10 were decreased, and IL-4 and IL-10 were significantly lower than those in normal controls （P〈0.01）. Th1/Th2 cytokine ratio （IL-2＋IFN-γ/IL-4- IL-5） was markedly higher in children with CITP than in healthy controls （P〈0. 01）, and which showed a negative correlation with peripheral platelet count （RR = 0. 2515, P=0. 0174）. The serum levels of TGF-β1 in CITP patients was significantly lower than that in normal controls（P〈0.01）. ②In the remission stage, Th2 type cytokines and the serum levels of TGF-β1 were markedly increased than that in the period of onset （P〈0. 01）, and Th1/Th2 cytokine ratio were markedly decreased in the period of onset （P〈 0. 01）. Conclusion Abnormal lymphocyte polarization phenomenon is indicated in children with CITP. In the period of onset, the lymphocytes in serum from children with CITP are mainly Thl which secreted IFN-γand IL-2, while Th2 which secreted IL-4,IL-5, IL-10 are increased in the remission stage and the serum levels of TGF-β1 was markedly increased. Th3 cytokines cooperated with Th2 cytokines exert negative immunoregulation and, consequently, platelet progressively rise. How to regulate Th1/Th2/ Th3 cytokine balance to normal levels in children with CITP deserve further study.