Capecchi Riccardo, Migliorini Paola, Zanzi Federico, Maltinti Simona, Puxeddu Ilaria, de Bortoli Nicola, Bellini Massimo, Costa Francesco, Marchi Santino, Bertani Lorenzo
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Front Pharmacol. 2021 Apr 9;12:654319. doi: 10.3389/fphar.2021.654319. eCollection 2021.
Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome. We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- <2) and mucosal healing (Mayo Endoscopic Score <2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched. Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS ( = 0.04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline ( = 0.04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy ( < 0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase ( = 0,2211; = 0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients ( = 0,0135 and = 0,0089, respectively). Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.
溃疡性结肠炎（UC）是一种慢性复发性疾病，需要持续监测，尤其是在生物治疗期间。越来越多的患者接受抗肿瘤坏死因子（TNF）药物治疗，目前的研究集中在识别能够监测疾病并预测治疗结果的生物标志物。我们纳入了连续接受抗TNF治疗且未使用过生物药物的UC患者。在治疗54周后，根据临床缓解（部分梅奥评分-PMS-<2）和黏膜愈合（梅奥内镜评分<2）评估治疗效果。对基线时和治疗54周后采集的血清样本进行基于凝集素的ELISA检测，并通过生物素标记的凝集素评估特定的糖基化模式。我们还收集了21例年龄和性别匹配的健康对照（NHS）样本。在纳入的44例UC患者中，22例在54周后实现了临床缓解和黏膜愈合。基线时，当使用蛋白A作为包被时，与NHS相比，UC无反应患者对Jacalin（JAC）的反应性降低（P = 0.04）。治疗一年后，与基线相比，仅在反应者中观察到JAC结合减少（P = 0.04）。当通过Fab抗IgG Fab选择IgG来检测JAC结合时，UC患者在抗TNF治疗后反应性增加（与对照组相比，P<0.0001）。基线时，当在固相使用Fab抗IgG Fab时，PMS与JAC结合呈负相关（r = -0.2211；P = 0.0033）。基线时PMS较高（PMS≥5）的患者与NHS以及PMS较低的患者相比，对JAC的结合能力较低（分别为P = 0.0135和P = 0.0089）。UC患者的Ig糖基化与临床和内镜活动相关。JAC蛋白A选择的Ig在预测治疗效果方面可能具有作用。如果这些数据得到证实，Ig糖基化可作为UC的生物标志物。
