溃疡性结肠炎患者肠黏膜固有层内炎症细胞比例预测黏膜组织学愈合的有效性研究

Study on the effectiveness of the proportion of inflammatory cells in the lamina propria of intestinal mucosa in predicting mucosal histological healing in patients with ulcerative colitis

目的确定更简便、实用的预测溃疡性结肠炎(UC)黏膜组织学愈合的评分标准。方法回顾性分析2017年4月11日至2021年2月8日在同济大学附属第十人民医院消化内科住院治疗且内镜下诊断为黏膜愈合的68例UC患者和同期行内镜检查的60名健康体检者的临床资料。根据收集的UC患者临床资料、内镜报告、组织病理学评估完成患者的改良梅奥评分、溃疡性结肠炎内镜下严重度指数(UCEIS)、Nancy指数和Robarts组织病理学指数,以及肠黏膜固有层内中性粒细胞、嗜酸性粒细胞和浆细胞的占比,并且根据CD177、CD40L确定肠黏膜固有层内活化的中性粒细胞和T细胞的占比。采用多因素logistic回归分析推导新的临床、实验室诊断公式,并采用受试者操作特征曲线(ROC)评估方程的有效性。结果68例UC患者中,改良梅奥评分为0.7分(0.4分,1.1分),UCEIS为0.5分(0.3分,0.8分),Nancy指数为(5.9±3.2)分,Robarts组织病理学指数为(2.6±1.7)分。根据多因素logistic回归分析得出临床诊断组织学愈合的公式为Y1=-21.09+355.9X_(1)+305.8X_(2)+44.91X_(3)(X_(1)、X_(2)、X_(3)分别为中性粒细胞、嗜酸性粒细胞、浆细胞的占比),ROC分析结果显示Y1<-0.747是诊断临床组织学愈合的临界值,曲线下面积(AUC)值为0.986,95%置信区间为0.922~1.000(P<0.001),灵敏度为97.10%,特异度为91.20%;实验室诊断组织学愈合的公式为Y2=-10.57+469.1X_(1)+132.7X_(2)+101.2X_(3)+18.56X_(4)(X_(1)、X_(2)、X_(3)、X_(4)分别为CD177阳性中性粒细胞、嗜酸性粒细胞、CD40L阳性T细胞和浆细胞的占比),ROC分析得出Y2<1.960是诊断组织学愈合的临界值,AUC值为0.980,95%置信区间为0.913~0.999(P<0.001),灵敏度为84.78%,特异度为100.00%。临床和实验室诊断新标准与组织学Nancy指数(r=0.411、0.308,P=0.001、0.011)和Robarts组织病理学指数(r=0.311、0.273,P=0.010、0.024)均呈正相关。结论临床和实验室诊断新标准相较于Nancy指数更简便、实用,新的临床诊断公式Y1<-0.747和实验室诊断公式Y2<1.960是预测UC患者组织学愈合的独立因素。

Objective To determine a simpler and more practical scoring standard for predicting mucosal histological healing in ulcerative colitis(UC).Methods From April 11,2017 to February 8,2021,68 UC patients diagnosed with mucosal healing under endoscopy and hospitalized at Department of Gastroenterology,the Tenth People′s Hospital of Tongji University and during the same period 60 healthy individuals who underwent endoscopy for health checkup were retrospectively analyzed.Modified Mayo score and ulcerative colitis endoscopic index of severity(UCEIS),the modified Nancy index and Robarts histopathology index were determined based on the collected clinical data,endoscopic reports and histopathological evaluation.The proportions of neutrophils,eosinophils,and plasma cells in the colonic mucosal lamina propria were calculated.The proportions of activated neutrophils and T cells in the colonic mucosal lamina were calculated according to CD177 and CD40L,respectively.The new clinical and laboratory diagnostic formulas were determined by multivariate logistic regression analysis,the effectiveness of the equations was evaluated by receiver operating characteristic curve(ROC).Results Among the 68 patients with UC,the modified Mayo score was 0.7(0.4,1.1),the UCEIS was 0.5(0.3,0.8),the Nancy index was 5.9±3.2,and the Robarts histopathology index was 2.6±1.7.According to multivariate logistic regression analysis,the formula for clinical diagnosis of histological healing was Y1=-21.09+355.9X_(1)+305.8X_(2)+44.91X_(3)(X_(1),X_(2) and X_(3) were the proportions of neutrophils,eosinophils,and plasma cells,respectively).The results of ROC analysis indicated that Y1<-0.747 was the cut-off value of diagnosis of histological healing,and the area under the curve(AUC)was 0.986 and 95%confidence interval(CI)was 0.922 to 1.000(P<0.001),the sensitivity was 97.10%and the specificity was 91.20%.The formula of laboratory diagnosis of histological healing was Y2=-10.57+469.1X_(1)+132.7X_(2)+101.2X_(3)+18.56X_(4)(X_(1),X_(2),X_(3),and X_(4) were the proportions of CD177+neutrophils,eosinophils,CD40L+T cells and plasma cells,respectively).The results of ROC analysis indicated that Y2<1.960 was the cut-off value of diagnosis of histological healing,and the AUC was 0.980,95%CI was 0.913 to 0.999(P<0.001),the sensitivity was 84.78%,and the specificity was 100.00%.The new clinical and laboratory diagnostic criteria were positively correlated with the Nancy histological index(r=0.411 and 0.308,P=0.001 and 0.011),and Robarts histopathology index(r=0.311,0.273,P=0.010 and 0.024).Conclusions Compared with the Nancy index,the new clinical and laboratory diagnostic criteria are simpler and more practical.The new clinical diagnostic formula Y1<-0.747 and the new laboratory diagnosis formula Y2<1.960 are the independent factors for predicting histological healing in UC patients.