National Institute of Gastroenterology-IRCCS, "Saverio de Bellis", 70013 Castellana Grotte, Italy.
Int J Mol Sci. 2023 Feb 16;24(4):3955. doi: 10.3390/ijms24043955.
Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and Ulcerative Colitis (UC), are multifactorial disorders characterized by a chronic inflammatory status with the secretion of cytokines and immune mediators. Biologic drugs targeting pro-inflammatory cytokines, such as infliximab, are broadly used in the treatment of IBD patients, but some patients lose responsiveness after an initial success. The research into new biomarkers is crucial for advancing personalized therapies and monitoring the response to biologics. The aim of this single center, observational study is to analyze the relationship between serum levels of 90K/Mac-2 BP and the response to infliximab, in a cohort of 48 IBD patients (30 CD and 18 UC), enrolled from February 2017 to December 2018. In our IBD cohort, high 90K serum levels were found at baseline in patients who then developed anti-infliximab antibodies at the fifth infusion (22 weeks after the first), becoming non-responders (9.76 ± 4.65 µg/mL compared to 6.53 ± 3.29 µg/mL in responder patients, = 0.005). This difference was significant in the total cohort and in CD, but not significant in UC. We then analyzed the relationship between serum levels of 90K, C-reactive protein (CRP), and Fecal calprotectin. A significant positive correlation was found at baseline between 90K and CRP, the most common serum inflammation marker (R = 0.42, = 0.0032). We concluded that circulating 90K could be considered a new non-invasive biomarker for monitoring the response to infliximab. Furthermore, 90K serum level determination, before the first infliximab infusion, in association with other inflammatory markers such as CRP, could assist in the choice of biologics for the treatment of IBD patients, thereby obviating the need for a drug switch due to loss of response, and so improving clinical practice and patient care.
炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC），是一种多因素疾病，其特征是存在慢性炎症状态，伴有细胞因子和免疫介质的分泌。针对促炎细胞因子的生物药物，如英夫利昔单抗，广泛用于治疗 IBD 患者，但有些患者在初始成功后会失去反应。因此，研究新的生物标志物对于推进个性化治疗和监测生物制剂的反应至关重要。本单中心观察性研究的目的是分析 48 例 IBD 患者（30 例 CD 和 18 例 UC）的血清 90K/Mac-2BP 水平与英夫利昔单抗反应之间的关系，这些患者于 2017 年 2 月至 2018 年 12 月入组。在我们的 IBD 患者队列中，基线时发现高血清 90K 水平的患者在第五次输注（第一次输注后 22 周）时产生抗英夫利昔单抗抗体，成为无反应者（9.76 ± 4.65 µg/mL 比反应者患者的 6.53 ± 3.29 µg/mL， = 0.005）。在总队列和 CD 中，这种差异具有统计学意义，但在 UC 中无统计学意义。然后我们分析了血清 90K、C 反应蛋白（CRP）和粪便钙卫蛋白之间的关系。基线时，90K 与最常见的血清炎症标志物 CRP 之间存在显著正相关（R = 0.42， = 0.0032）。我们得出结论，循环 90K 可被视为监测英夫利昔单抗反应的新的非侵入性生物标志物。此外，在第一次英夫利昔单抗输注之前，测定血清 90K 水平，并结合 CRP 等其他炎症标志物，可能有助于选择生物制剂治疗 IBD 患者，从而避免因失去反应而需要更换药物，从而改善临床实践和患者护理。
