Yu Hsin-Hui, Liu Pi-Hua, Yang Yao-Hsu, Lee Jyh-Hong, Wang Li-Chieh, Chen Wei-J, Chiang Bor-Luen
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Tao-Yuan, Taiwan, ROC.
J Formos Med Assoc. 2015 Apr;114(4):347-52. doi: 10.1016/j.jfma.2012.12.007. Epub 2013 Feb 1.
BACKGROUND/PURPOSE: Henoch-Schönlein purpura (HSP) is the most common small vessel vasculitis in children. It is considered to be an IgA-containing immune complex-mediated disease. Chemokines are small secreted proteins that attract leukocytes during inflammation. Our aim was to determine the serum levels of chemokines and investigate the association of chemokine gene polymorphisms with childhood HSP.
Serum levels of chemokines (interleukin-8/CXCL8, MCP-1/CCL2, RANTES/CCL5, MIG/CXCL9, and IP-10/CXCL10) were determined using cytometric beads arrays. We investigated the association of three single-nucleotide polymorphisms (SNPs) MCP1/CCL2 -2518C/T, RANTES/CCL5 -403C/T, and RANTES/CCL5 -28C/G with HSP in 85 HSP patients and 136 healthy controls.
Five serum chemokine levels were significantly elevated in patients with the acute stage of HSP compared to the normal controls (p < 0.05). MCP1/CCL2 -2518 TT genotype and T allele were associated with the risk for HSP with OR (95% CI) 3.32 (1.45-7.59) and 1.78 (1.20-2.64), respectively. The RANTES/CCL5 -28 GG genotype was associated with a significantly lower percentage of corticosteroid usage and lower corticosteroid accumulative dose in HSP patients. RANTES/CCL5 -403 TC and TT genotype were significantly associated with renal manifestations with an OR (95% CI) of 4.33 (1.44-12.99), adjusted for sex and age and the other two SNP genotypes.
Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis.
背景/目的：过敏性紫癜（HSP）是儿童最常见的小血管炎。它被认为是一种含IgA的免疫复合物介导的疾病。趋化因子是在炎症过程中吸引白细胞的小分泌蛋白。我们的目的是测定趋化因子的血清水平，并研究趋化因子基因多态性与儿童HSP的关联。
使用细胞计数珠阵列测定趋化因子（白细胞介素-8/CXCL8、单核细胞趋化蛋白-1/CCL2、调节激活正常T细胞表达和分泌因子/CCL5、γ干扰素诱导的单核因子/CXCL9和干扰素诱导蛋白10/CXCL10）的血清水平。我们在85例HSP患者和136例健康对照中研究了三个单核苷酸多态性（SNP），即MCP1/CCL2 -2518C/T、RANTES/CCL5 -403C/T和RANTES/CCL5 -28C/G与HSP的关联。
与正常对照相比，HSP急性期患者的五种血清趋化因子水平显著升高（p<0.05）。MCP1/CCL2 -2518 TT基因型和T等位基因与HSP风险相关，OR（95%CI）分别为3.32（1.45-7.59）和1.78（1.20-2.64）。RANTES/CCL5 -28 GG基因型与HSP患者使用皮质类固醇的百分比显著降低和皮质类固醇累积剂量降低相关。在根据性别、年龄以及其他两个SNP基因型进行校正后，RANTES/CCL5 -403 TC和TT基因型与肾脏表现显著相关，OR（95%CI）为4.33（1.44-12.99）。
我们的结果支持趋化因子在HSP发病机制中起重要作用这一事实。MCP1/CCL2基因多态性与HSP易感性相关。RANTES/CCL5基因多态性可能与疾病严重程度和HSP肾炎有关。
