Mendieta-Escalante Erick A, Faber Klaas Nico, Dijkstra Gerard
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Eur J Immunol. 2025 Aug;55(8):e51721. doi: 10.1002/eji.202451721.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation and epithelial barrier dysfunction. Circulating autoantibodies have been observed in many patients, suggesting a role in disease pathogenesis and progression. Atypical anti-neutrophil cytoplasmic antibodies (a-ANCAs), anti-goblet cell antibodies (GAB), and anti-integrin αvβ6 antibodies have emerged as promising biomarkers for UC diagnosis, disease monitoring, and therapeutic response prediction. a-ANCAs are detected in up to 80% of UC patients, but their precise antigenic targets remain unclear. Evidence suggests their reactivity may involve neutrophil extracellular traps (NETs) and DNA-protein complexes, distinguishing them from ANCAs in vasculitis. GAB may contribute to mucus layer depletion and epithelial dysfunction. Anti-integrin αvβ6 antibodies have demonstrated high specificity for UC related to disease severity and potential for early detection. Despite the diagnostic potential of these autoantibodies, lack of standardization, variability in detection methods, unclear binding sites, and lack of relevant clinical studies limit their use in clinical practice. Advances in epitope mapping, flow cytometry, and high-throughput immunoassays are promising approaches. We review the role of these autoantibodies in UC pathogenesis, highlight recent developments, and discuss their potential as biomarkers for improving diagnosis, disease monitoring, and personalized treatment strategies for UC patients.
溃疡性结肠炎(UC)是一种慢性炎症性肠病,其特征为免疫失调和上皮屏障功能障碍。许多患者体内已检测到循环自身抗体,提示其在疾病发病机制和进展中发挥作用。非典型抗中性粒细胞胞浆抗体(a-ANCA)、抗杯状细胞抗体(GAB)和抗整合素αvβ6抗体已成为UC诊断、疾病监测及治疗反应预测的有前景的生物标志物。高达80%的UC患者可检测到a-ANCA,但其确切抗原靶点仍不清楚。有证据表明,它们的反应性可能涉及中性粒细胞胞外诱捕网(NETs)和DNA-蛋白质复合物,这使其与血管炎中的ANCA有所区别。GAB可能导致黏液层减少和上皮功能障碍。抗整合素αvβ6抗体对与疾病严重程度相关的UC具有高特异性,且有早期检测的潜力。尽管这些自身抗体具有诊断潜力,但缺乏标准化、检测方法的变异性、结合位点不明确以及缺乏相关临床研究限制了它们在临床实践中的应用。表位作图、流式细胞术和高通量免疫测定方面的进展是有前景的方法。我们综述了这些自身抗体在UC发病机制中的作用,强调了最近的进展,并讨论了它们作为生物标志物在改善UC患者诊断、疾病监测和个性化治疗策略方面的潜力。