Objective: To investigate the diagnostic and evaluation value of plasma interleukin 9 (IL9) in the mucosal healing (MH) in patients with inflammatory bowel disease (IBD) treated with biological agents. Methods: Cohort study. IBD patients (137 cases) treated in the Affiliated Suzhou Hospital to Nanjing Medical University (Suzhou Municipal Hospital) from September 2019 to January 2022 were prospective selected. Each patient was treated with biological agents [Infliximab (IFX, 56 cases), Adalimumab (ADA, 20 cases), Ustekinumab (UST, 18 cases), Vedolizumab (VDZ, 43 cases)]. According to different therapeutic drugs, the IFX, ADA, UST, and VDZ group were divided. Clinical symptoms, inflammatory indicators and imaging examinations etc. were evaluated every 8 weeks, and the degree of MH was evaluated by endoscopy at the 54th week. The expression of plasma IL9 was detected by ELISA after initial enrollment (W 0) and 8 weeks of biological treatment (W 8). Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of IL9 for MH. Select the cut off value for the optimal ROC threshold based on the highest value of the Youden index. Spearman's rank correlation was used to analyze the correlation between IL9 and Simple Endoscopic Score for CD (SES-CD) and Mayo Endoscopic Score (MES), so as to evaluate the predictive value of IL9 for MH in IBD patients treated with biologic agents. Results: Among the 137 patients, there were 97 Crohn's disease (CD) patients, 53 males and 44 females, aged (31.6±10.3) years (18-60 years). There were 40 ulcerative colitis (UC) patients, 22 males and 18 females, aged (37.5±14.7) years (18-67 years). Among the CD patients, 42 cases (43.3%) achieved MH on endoscopy at the 54th week, and 60 patients (61.9%) achieved clinical remission. Among the UC patients, 22 cases (55.0%) achieved MH and 30 cases (75.0%) achieved clinical remission. At W 0, the relative expression of IL9 in patients in IBD patients who achieved MH after 54 weeks of biological treatment was lower than that in the non-MH patients [x¯±s, (127.42±34.43) vs (146.82±45.64) ng/L, (113.01±44.88) vs (146.12±48.66) ng/L, respectively, both P<0.05]. At W 8, the relative expression of IL9 in the MH group was lower than that in the non-MH patients (both P<0.05). The relative expression of IL9 in the MH patients after IFX treatment was lower than that in the non-MH group (P<0.05). There was no significant difference among the other groups between MH and non-MH patients (all P>0.05). IL9 at W 8 showed high value in predicting MH in IBD [CD patients: area under curve (AUC)=0.716(95%CI: 0.616-0.817, P<0.001), sensitivity and specificity were 80.77%(95%CI:67.64%-88.45%) and 48.89%(95%CI: 35.53%-64.47%), respectively; UC patients: AUC=0.821, sensitivity and specificity were 77.78% and 72.73%, respectively]. At W 8, the cut off values for CD and UC patients were IL9>80.77 ng/L and IL9>77.78 ng/L, respectively. IL9 was positively correlated with endoscopic MH score parameters [M(Q1,Q3),SES-CD: 3.0(8.5, 18.5); MES: 2.0(1.0, 3.0)] (r=0.55, 0.72, respectively, both P<0.001) at W8. Conclusion: The plasma IL-9 at the week 8 after biological agents treatment can be used to diagnose and evaluate the MH of patients with IBD.
目的： 探讨血浆白细胞介素9（IL9）对生物制剂治疗后的炎性肠病（IBD）患者黏膜愈合的诊断及评估价值。 方法： 随访研究。前瞻性选取2019年9月至2022年1月在南京医科大学附属苏州医院（苏州市立医院）就诊的137例IBD患者，分别使用生物制剂英夫利昔单抗（IFX，56例）、阿达木单抗（ADA，20例）、乌司奴单抗（UST，18例）和维得利珠单抗（VDZ，43例）治疗；根据治疗药物不同，分为IFX组、ADA组、UST组和VDZ组。每8周评估1次（包括临床症状、炎症指标、影像学检查等），第54周时行内镜评估黏膜愈合程度。ELISA法检测入组时（W 0）和生物制剂治疗8周（W 8）后血浆IL9的表达量。受试者工作特征（ROC）曲线评估IL9对黏膜愈合的诊断效能。根据约登指数的最高值选择最佳ROC曲线阈值的截止值。Spearman等级相关分析IL9与克罗恩病简化内镜评分（SES-CD评分）、梅奥内镜评分（MES评分）间的相关性，以评估W 0和W 8时IL9对生物制剂治疗54周时的IBD患者黏膜愈合的预测价值。 结果： 137例患者中，有97例克罗恩病（CD）患者，男53例，女44例，年龄（31.6±10.3）岁（18~60岁）；有40例溃疡性结肠炎（UC）患者，男22例，女18例，年龄（37.5±14.7）岁（18~67岁）。CD患者中，42例患者（43.3%）第54周内镜检查提示黏膜愈合；60例（61.9%）获得临床缓解。UC患者中，22例（55.0%）达到黏膜愈合；30例（75.0%）获得临床缓解。W 0时，黏膜愈合的CD和UC患者的IL9相对表达量均低于未愈合的患者［x¯±s，分别为（127.42±34.43）比（146.82±45.64）ng/L，（113.01±44.88）比（146.12±48.66）ng/L，均P<0.05］。W 8时，黏膜愈合的CD和UC患者的IL9相对表达量均低于未愈合的患者（均P<0.05）。IFX治疗后黏膜愈合的患者的IL9相对表达量低于未达到黏膜愈合的患者（P<0.05）；其他治疗组患者黏膜愈合与未愈合间的差异均无统计学意义（均P>0.05）。W 8时IL9对预测IBD黏膜愈合具有较高的预测价值［CD患者：ROC曲线下面积（AUC）=0.716（95%CI：0.616~0.817，P<0.001），灵敏度和特异度分别为80.77%（95%CI：67.64%~88.45%）和48.89%（95%CI：35.53%~64.47%）；UC患者：AUC=0.821，灵敏度和特异度分别为77.78%和72.73%］，CD和UC患者的cut off值分别为IL9>80.77 ng/L、IL9>77.78 ng/L。W 8时，IL9与内镜下黏膜愈合参数［M（Q1，Q3），SES-CD评分：3.0（8.5，18.5）；MES评分：2.0（1.0，3.0）］均呈正相关（分别r=0.55、0.72，均P<0.001）。 结论： 生物制剂治疗第8周时的血浆IL9可用于诊断和评估IBD患者的黏膜愈合情况。.