克罗恩病患者血清可溶性细胞毒T淋巴细胞相关抗原4水平高表达及其临床意义

High levels of serum soluble cytotoxic T lymphocyte associated antigen 4 and its clinical significance in patients with Crohn＇s disease

目的 研究可溶性细胞毒T淋巴细胞相关抗原4（sCTLA4）在克罗恩病（CD）患者血清中的表达状况,分析sCTLA4水平与红细胞沉降率（ESR）和C反应蛋白（CRP）的关系及其临床意义,探讨CTLA4基因-1661A/G和-1722T/C多态性与CD的相关性.方法 收集126例CD患者和300名健康对照者,酶联免疫吸附实验测定血清sCTLA4水平.全自动红细胞沉降系统分析仪测定ESR水平.速率散射比浊法测定CRP水平.DNA测序技术检测CTLA4基因-1661A/G和-1722T/C多态性.结果 CD患者血清中sCTLA4水平为（18.70±3.72）ng/ml,明显高于健康对照者[（1.72±0.32）ng/ml,P＜0.01].活动期CD患者血清sCTLA4水平为（19.83±4.35）ng/ml,比缓解期CD患者[（18.02±3.14）ng/ml,P=0.015]增高.CD患者血清sCTLA4水平与ESR和CRP水平呈正相关（r=0.267,P=0.003;r=0.524,P＜0.01）.疾病行为影响CD患者血清sCTLA4水平,狭窄型CD患者血清sCTLA4水平高于非狭窄非穿透型和穿透型CD患者,差异均有统计学意义（P值分别=0.021和0.015）.CD组和健康对照组中CTLA4基因-1661A/G,-1722T/C等位基因及基因型频率差异无统计学意义（P＞0.05）.结论 CD患者血清sCTLA4水平增高,增高的sCTLA4水平不仅与疾病活动状态及狭窄型疾病行为相关,且与CRP正相关,提示sCTLA4分子在CD免疫学发病中可能起重要作用.

Objective To investigate the expression of serum soluble cytotoxic T lymphocyte associated antigen 4 （sCTLA4）, the association of sCTLA4 level with erythrocyte sedimentation rate （ESR） and C reactive protein （CRP）, as well as its role in patients with Crohn＇s disease （CD）. The relationship-1661A/G and -1722T/C polymorphisms of CTLA4 gene and between disease susceptibility and phenotype of CD was analyzed. Methods A total of 126 CD patients and 300 healthy controls were enrolled in the study. Serum sCTLA4 level was determined by enzyme-linked immunosorbent assay. The concentrations of ESR and CRP were analyzed by automatic ESR Analyzer SRS 100/Ⅱ and rate nephelometry, respectively. The polymorphisms of CTLA4-1661A/G and -1722 T/C were genotyped by DNA sequencing. Results Serum sCTLA4 level was higher in CD patients than in healthy controls [（18. 70±3. 72） ng/ml vs （1.72±0. 32） ng/ml, P＜0. 01）]. Among CD patients, sCTLA4 level was higher in patients with active disease when compared to those with inactive disease [（19.83±4.35） ng/ml vs （18. 02±3.14） ng/ml, P=0. 015）]. sCTLA4 level was positively correlated with ESR and CRP levels （r=0. 267, P=0. 003; r=0. 524 P ＜0.01, respectively）. In CD patients, serum sCTLA4 level was significantly higher in those with stricturing disease behavior than that in those without stricturing and penetrating or with penetrating disease behavior （P= 0.021; P=0. 015, respectively）. Detection of CTLA4 -1661A/G and -1722T/C polymorphisms showed no significant difference between CD patients and healthy controls. Conclusions The high level of serum sCTLA4 in CD patients is correlated with disease activity, CRP levels and disease behavior. It suggests that sCTLA4 may play an important role in pathogenesis of CD.