Caviglia Gian Paolo, Rosso Chiara, Stalla Francesco, Rizzo Martina, Massano Alessandro, Abate Maria Lorena, Olivero Antonella, Armandi Angelo, Vanni Ester, Younes Ramy, Fagoonee Sharmila, Pellicano Rinaldo, Astegiano Marco, Saracco Giorgio Maria, Bugianesi Elisabetta, Ribaldone Davide Giuseppe
Department of Medical Sciences, University of Turin, 1016 Turin, Italy.
Unit of Gastroenterology, Città della Salute e della Scienza di Torino-Molinette Hospital, 10126 Turin, Italy.
J Clin Med. 2020 Mar 15;9(3):800. doi: 10.3390/jcm9030800.
In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission ( = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS ( = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn's disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25-18.02, = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.
在接受生物治疗的炎症性肠病(IBD)患者中,治疗反应的生物标志物仍然匮乏。本研究旨在评估血清连蛋白(一种肠道通透性生物标志物)、可溶性CD163(sCD163,一种巨噬细胞活化标志物)以及一组血清细胞因子是否能够预测IBD患者对生物治疗的反应。为此,我们前瞻性纳入了101例IBD患者和19例肠易激综合征(IBS)患者作为对照组;101例患者中有60例接受了生物制剂治疗。在所有患者基线时以及接受生物治疗的60例患者治疗10周后,检测了连蛋白、sCD163和细胞因子。我们观察到,与缓解期IBD患者相比,活动期IBD患者的连蛋白水平更高(P = 0.035),且与IBS患者相比,IBD患者的sCD163值更高(P = 0.042),但未观察到这两种生物标志物与治疗反应有相关性。相反,白细胞介素(IL)-6、IL-8、IL-10和肿瘤坏死因子-α从基线到治疗第10周有显著降低,尤其是在有反应的患者中。通过对疾病(克罗恩病或溃疡性结肠炎)、生物药物类型(英夫利昔单抗、阿达木单抗、维多珠单抗或乌司奴单抗)和疾病活动进行校正的多因素逻辑回归分析,IL-6值的降低与生物治疗12个月时的临床反应相关(比值比(OR)= 4.75,95%置信区间(CI)1.25 - 18.02,P = 0.022)。总之,检测接受生物制剂治疗的IBD患者的血清IL-6水平可能有助于预测治疗12个月时的反应,从而有助于制定个性化治疗策略。