Correlation of contact system activation with occurrence of thrombotic events in patients with systemic lupus erythematosus / 中华危重病急救医学

ABSTRACT

Objective To explore the role of contact system activation in the mechanism of systemic lupus erythematosus (SLE) patients with thrombotic events.Methods A simple sample drawing study was conducted.Sixty-nine patients with SLE admitted to Department of Rheumatism in Tianjin Hospital from June 2014 to February 2016 were enrolled.The patients were divided into simple SLE group (n =38) and SLE + vascular diseases (VD) group (n =31) according to whether the patients complicated with VD or not.The VD patients were subdivided into three subgroups including SLE complicated with myocardial infarction (SLE + MI,n =10),SLE complicated with deep vein thrombosis (SLE + DVT,n =13),and SLE complicated with arterial thrombosis (SLE + AT,n =8).Sixty-eight healthy age and gender-matched volunteers without history of VD were served as controls.Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of FⅫa-C1 inhibitor (FⅫa-C1INH) and FⅫa-antithrombin (FⅫa-AT) in plasma.Flow cytometry was used to analyze the contents of platelets associated factors.The correlation between platelet associated factor and FⅫA-C1INH and FⅫa-AT was analyzed by Spearman correlation analysis.Receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of FⅫA-C1INH and FⅫa-AT for SLE thrombotic events.Results Compared with health control group,the expression of FⅫa-C1INH in plasma in SLE group was significantly decreased [nmol/L0.00 (0.00,0.07) vs.0.08 (0.03,0.13),P ＜ 0.01],the expression of FⅫa-AT was significantly up-regulated [nmol/L0.18 (0.07,0.38) vs.0.16 (0.12,0.26),P ＜ 0.05].Compared with the simple SLE group,the expression of FⅫa-C1INH in SLE + DVT and SLE + AT groups was significantly decreased [nmol/L0.03 (0.02,0.07),0.02 (0.01,0.04) vs.0.07 (0.02,0.11),both P ＜ 0.05],and the expression of FⅫa-AT in plasma in SLE + AT group was significantly increased [nmol/L0.34 (0.21,0.53) vs.0.17 (0.06,0.30),P ＜ 0.01].It was shown by correlation analysis that FⅫa-C1INH was negatively related with FⅫa-AT in patients with SLE (r =-0.24,P =0.041 6).Activated platelet associated factors such as the production of interferon mediated by transmembrane protein 1 (IFTMI1) and interferon induced by double stranded RNA dependent activation agent (PRKRA) were positively related with up-regulation of FⅫa-AT and down-regulation of FⅫa-C1INH (IFITM1 and FⅫa-ATr =0.39,P =0.001 2;IFITM1 and FⅫa-C1INHr =-0.30,P =0.0146;PRKRA and FⅫa-ATr =0.29,P =0.017 6;PRKRA and FⅫa-C1INHr =-0.36,P =0.0029).The thrombospondin-1 (TSP-1) and platelet P-selectin were positively related with up-regulation of FⅫa-AT (r1 =0.72,P1 ＜ 0.0001;r2 =0.34,P2 =0.003 8).It was shown by ROC curve analysis that the area under the ROC curve (AUC) for FⅫa-C1INH on evaluating the risk of SLE thrombotic events was 0.998,the sensitivity was 100％,and specificity was 97.4％ when cut-off ＜ 0.01 nmol/L;AUC for FⅫa-AT for evaluating the risk of SLE thrombotic events was 0.954,the sensitivity was 95.0％,and specificity was 84.2％ when cut-off ＞ 0.40 nmol/L;predicted probability of two markers for predicting diagnosis was 0.5,the sensitivity and specificity were both 100％.Conclusions Contact system is activated in patients with SLE.FⅫA-C1INH and FⅫa-AT levels are closely related with platelet associated factors IFITM1 and PRKRA.FⅫA-C1INH and FⅫa-AT can be served as a promising potential biomarker for evaluation of the risk of thrombotic events in SLE.