目的评价CD8~+CD28~+/CD8~+CD28-T细胞平衡在预测炎症性肠病(IBD)患者并发消化道出血(GH)的作用与价值。方法收集IBD患者49例,其中溃疡性结肠炎(UC)30例,克罗恩病(CD)19例,使用流式细胞术检测外周血CD8~+CD28~+及CD8~+CD28-T细胞T细胞的百分含量,对患者进行为期1年的随访,使用受试者工作特征(ROC)曲线法评价CD8~+CD28~+/CD8~+CD28-T细胞平衡(比值)在预测IBD患者出现GH的效能,并使用Kaplan-Meier生存分析法比较不同因素下的持续缓解时间(LTR)差异,并对相关指标进行相关性分析。结果 (1)CD组的免疫抑制剂、激素及生物制剂(BA)使用率均显著高于UC组(P=0.003、0.043及0.002);(2)UC组患者的CD8~+CD28~+T细胞显著高于CD组(t=3.022,P=0.004);(3)ROC结果显示CD8~+CD28~+T细胞、CD8~+CD28-T细胞及CD8~+CD28~+/CD8~+CD28-比值三者在预测GH方面均具有良好的效能(均为P〈0.01),但以CD8~+CD28~+/CD8~+CD28-最优[曲线下面积(AUC)为0.977,P=0.000],截值分析显示当CD8~+CD28~+/CD8~+CD28-比值取值为1.14时(13.95%/12.24%),其对应的敏感度达93.3%,特异度为91.2%;(4)未使用BA及未行手术治疗的IBD患者算术及中位LTR均显著长于使用BA及已行手术的IBD患者(分别为χ2=9.730,P=0.002;χ2=15.981,P=0.000);(5)Spearman分析显示CD8~+CD28~+/CD8~+CD28-与BA及手术均成显著相关性(P=0.009、0.038)。结论外周血CD8~+CD28~+T细胞降低或CD8~+CD28-T细胞升高与IBD患者出现GH密切相关,CD8~+CD28~+/CD8~+CD28-平衡预测GH的敏感度及特异度均高,尤其是在比值为1.14时;该平衡与生物制剂及手术存在显著相关性。
Objective To evaluate the sensitivity and specificity of CD8~+CD28~+/CD8~+CD28-T lymphocyte balance in predicting the gastrointestinal hemorrhage(GH) in patients with inflammatory bowel disease(IBD). Methods Forty-nine IBD patients,including 30 with ulcerous colitis(UC) and 19 with Crohn's disease(CD), were enrolled to test peripheral blood CD8~+CD28~+and CD8~+CD28-T cells using flow cytometry. All the patients were followed up for one year. The receiver-operating characteristic(ROC) curves were used to test the efficiency of CD8~+CD28~+/CD8~+CD28-T lymphocyte balance to predict GH. The differences in lasting time of remission(LTR) under different factors were compared using Kaplan-Meier survival analysis, and the correlation between CD8~+T lymphocytes and the factors were analyzed. Results The utilization rates of immunosuppressant, steroids, and biological agent(BA) were significantly higher in CD patients than in UC patients(P=0.003, 0.043 and 0.002,respectively). The frequencies of CD8~+CD28~+T cells were obviously higher in UC patients than those in CD patients(t=3.022, P=0.004). CD8~+CD28~+T cells, CD8~+CD28-T cells, and especially CD8~+CD28~+/CD8~+CD28-ratio(area under curve of 0.977, P=0.000;cut-off value of 1.14 [13.95%/12.24%] with a sensitivity of 93.3% and a specificity of 91.2%) showed good efficiencies in predicting GH(P0.01). The mean and median of LTR of IBD patients who did not receive BA or surgical treatment were significantly longer(χ2=9.730, P=0.002; χ2=15.981, P=0.000). CD8~+CD28~+/CD8~+CD28-ratio was significantly related to both BA(P=0.009) and surgery(P=0.038). Conclusion Both decreased CD8~+CD28~+T cells and elevated CD8~+CD28-T cells are closely correlated with GH, and their ratio can predict the occurrence of GH with a high sensitivity and specificity and is correlated with BA and surgery at the cut-off value of 1.14.