Chang Hong, Zhang Qiu-Ye, Lin Yi, Cheng Na, Zhang Shou-Qing
Department of Pediatric Cardiology Nephrology and Rheumatism, The Affiliated Hospital of Qingdao University Medical College Qingdao 266003, China.
Department of pediatrics, Qianfo Hill institute of Shandong Province Jinan 250014, China.
Int J Clin Exp Med. 2015 Aug 15;8(8):13532-9. eCollection 2015.
We discussed the correlation of TLR2 (Toll-like receptor) and TLR4 expressions in peripheral blood mononuclear cells (PBMCs) to Th1- and Th2-type immune responses in children with Henoch-Schönlein Purpura (HSP). The role of TLR2 and TLR4 in the pathogenesis of HSP was analyzed. Sixty-four HSP children treated at our hospital from October 2011 to November 2012 were enrolled and divided into NHSPN group (complicated by renal impairment, 36 cases) and HSPN group (not complicated by renal impairment, 28 cases). In the meantime, 30 normal children receiving physical examination at our hospital were recruited as controls. Peripheral blood T cell subgroups and TLR2 and TLR4 expressions in PBMCs were detected by using flow cytometry; relative expression levels of TLR2 and TLR4 mRNA in PBMCs by real-time quantitative fluorescence PCR, and plasma levels of IFN-γ, IL-4 and IL-6 by ELISA method. Relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in children with HSP were significantly higher than those of the controls (P<0.01). The relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in HSPN group were obviously higher than those in NHSPN group (P<0.05; P<0.01; P<0.01; P<0.01); CD3(+) T cells and CD3(+)CD4(+) T cells in HSP group were significantly decreased, while CD3(+)CD8(+) T cells and CD3(+)HLADR(+) T activated cells were considerably increased (P<0.01); The plasma levels of IL-4 and IL-6 in HSP group were significantly higher than those of the normal controls (P<0.01, P<0.01); IFN-γ level in the former was much lower than in the control group (P<0.05); IFN-γ/IL-4 ratio in the former was also lower than that in the control (P<0.01); TLR2 and TLR4 expressions in HSP group showed significantly positive correlation with the plasma levels of IL-4 and IL-6 (P<0.01, P<0.05; P<0.01, P<0.01) and significantly negative correlation with IFN-γ/IL-4 ratio (P<0.01; P<0.01). TLR2 and TLR4 activation may be involved in the pathogenesis of HSP. TLR2 and TLR4 overactivation may induce HSP-related renal impairment; Children with HSP showed T-cell disorders and Th1/Th2 imbalance. Activated TLR2 and TLR4 possibly mediate the pathogenesis of HSP by upregulating Th2-type immune responses.
我们探讨了过敏性紫癜（HSP）患儿外周血单个核细胞（PBMCs）中Toll样受体2（TLR2）和TLR4表达与Th1型和Th2型免疫反应的相关性。分析了TLR2和TLR4在HSP发病机制中的作用。选取2011年10月至2012年11月在我院治疗的64例HSP患儿，分为NHSPN组（合并肾脏损害，36例）和HSPN组（未合并肾脏损害，28例）。同时，选取30例在我院体检的正常儿童作为对照。采用流式细胞术检测外周血T细胞亚群及PBMCs中TLR2和TLR4的表达；采用实时定量荧光PCR检测PBMCs中TLR2和TLR4 mRNA的相对表达水平，采用酶联免疫吸附测定法检测血浆中IFN-γ、IL-4和IL-6水平。HSP患儿PBMCs中TLR2和TLR4 mRNA的相对表达水平及TLR2和TLR4蛋白表达均显著高于对照组（P<0.01）。HSPN组PBMCs中TLR2和TLR4 mRNA的相对表达水平及TLR2和TLR4蛋白表达均明显高于NHSPN组（P<0.05；P<0.01；P<0.01；P<0.01）；HSP组CD3(+)T细胞和CD3(+)CD4(+)T细胞显著减少，而CD3(+)CD8(+)T细胞和CD3(+)HLADR(+)T活化细胞显著增加（P<0.01）；HSP组血浆IL-4和IL-6水平显著高于正常对照组（P<0.01，P<0.01）；前者IFN-γ水平显著低于对照组（P<0.05）；前者IFN-γ/IL-4比值也低于对照组（P<0.01）；HSP组TLR2和TLR4表达与血浆IL-4和IL-6水平呈显著正相关（P<0.01，P<0.05；P<0.01，P<0.01），与IFN-γ/IL-4比值呈显著负相关（P<0.01；P<0.01）。TLR2和TLR4激活可能参与HSP的发病机制。TLR2和TLR4过度激活可能诱发HSP相关肾脏损害；HSP患儿存在T细胞紊乱及Th1/Th2失衡。活化的TLR2和TLR4可能通过上调Th2型免疫反应介导HSP的发病机制。
