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[血浆白细胞介素9在生物制剂治疗的炎症性肠病患者黏膜愈合中的诊断及评估价值]

[The diagnostic and evaluation value of plasma interleukin 9 in the mucosal healing in patients with inflammatory bowel disease treated with biological agents].

作者信息

Ye Y L, Hu T, Xu L J, Zhang L P, Yin J, Yu Q, Pang Z

机构信息

Department of Gastroenterology, the Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou 215008, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2023 May 23;103(19):1483-1489. doi: 10.3760/cma.j.cn112137-20221009-02110.

Abstract

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. 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. 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 <0.05]. At W 8, the relative expression of IL9 in the MH group was lower than that in the non-MH patients (both <0.05). The relative expression of IL9 in the MH patients after IFX treatment was lower than that in the non-MH group (<0.05). There was no significant difference among the other groups between MH and non-MH patients (all >0.05). IL9 at W 8 showed high value in predicting MH in IBD [CD patients: area under curve (AUC)=0.716(95%: 0.616-0.817, <0.001), sensitivity and specificity were 80.77%(95%:67.64%-88.45%) and 48.89%(95%: 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 [(,),SES-CD: 3.0(8.5, 18.5); MES: 2.0(1.0, 3.0)] (=0.55, 0.72, respectively, both <0.001) at W8. 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.

摘要

探讨血浆白细胞介素9(IL9)在接受生物制剂治疗的炎症性肠病(IBD)患者黏膜愈合(MH)中的诊断及评估价值。队列研究。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)接受治疗的IBD患者(137例)。每位患者均接受生物制剂治疗[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)、维多珠单抗(VDZ,43例)]。根据不同治疗药物分为IFX组、ADA组、UST组和VDZ组。每8周评估临床症状、炎症指标及影像学检查等,在第54周通过内镜评估MH程度。在初始入组时(W 0)及生物治疗8周后(W 8)采用酶联免疫吸附测定(ELISA)法检测血浆IL9表达。采用受试者工作特征曲线(ROC)评估IL9对MH的诊断效能。根据约登指数最大值选择最佳ROC阈值的截断值。采用Spearman等级相关分析IL9与克罗恩病简易内镜评分(SES-CD)及梅奥内镜评分(MES)之间的相关性,以评估IL9对接受生物制剂治疗的IBD患者MH的预测价值。137例患者中,克罗恩病(CD)患者97例,男53例,女44例,年龄(31.6±10.3)岁(18 - 60岁)。溃疡性结肠炎(UC)患者40例,男22例,女18例,年龄(37.5±14.7)岁(18 - 67岁)。CD患者中,42例(43.3%)在第54周内镜检查时达到MH,60例(61.9%)达到临床缓解。UC患者中,22例(55.0%)达到MH,30例(75.0%)达到临床缓解。在W 0时,生物治疗54周后达到MH的IBD患者中IL9的相对表达低于未达到MH的患者[均数±标准差,分别为(127.42±34.43)与(146.82±45.64)ng/L,(113.01±44.88)与(146.12±48.66)ng/L,均<0.05]。在W 8时,MH组中IL9的相对表达低于未达到MH的患者(均<0.05)。IFX治疗后达到MH的患者中IL9的相对表达低于未达到MH组(<0.05)。其他组中达到MH与未达到MH的患者之间无显著差异(均>0.05)。W 8时的IL9在预测IBD患者的MH方面显示出较高价值[CD患者:曲线下面积(AUC)=0.716(95%:0.616 - 0.817,<0.001),敏感性和特异性分别为80.77%(95%:67.64% - 88.45%)和48.89%(95%:35.53% - 64.47%);UC患者:AUC = 0.821,敏感性和特异性分别为77.78%和72.73%]。在W 8时,CD和UC患者的截断值分别为IL9>80.77 ng/L和IL > 77.78 ng/L。在W8时,IL9与内镜MH评分参数呈正相关[(,),SES-CD:3.0(8.5,18.5);MES:2.0(1.0,3.0)](分别为r = 0.55,0.72,均<0.001)。生物制剂治疗8周后的血浆IL - 9可用于诊断和评估IBD患者的MH。

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