Roth Dominik, Düll Miriam M, Horst Ludwig J, Lindemann Aylin, Malzer Xenia, Koop Kristina, Zundler Sebastian, Vetter Marcel, Jefremow André, Atreya Raja, Geppert Carol, Weidemann Sören, Waldner Maximilian J, Dietrich Peter, Günther Claudia, Munoz Luis E, Herrmann Martin, Scheffold Alexander, Neurath Markus F, Siebler Jürgen, Schramm Christoph, Kremer Andreas E, Leppkes Moritz
Department of Medicine 1, Gastroenterology, Pneumology and Endocrinology, Friedrich Alexander University Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
J Crohns Colitis. 2025 Feb 4;19(2). doi: 10.1093/ecco-jcc/jjae131.
Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified that are strongly associated with ulcerative colitis (UC). We aimed to elucidate whether anti-integrin αVβ6 (anti-αVβ6) is present in primary sclerosing cholangitis (PSC), its associated inflammatory bowel disease, or other cholestatic liver diseases and their persistence after proctocolectomy.
We detected anti-αVβ6 by an enzyme-linked immunosorbent assay in sera collected at 2 German tertiary centers, including healthy controls (N = 62), UC (N = 36), Crohn's disease (CD, N = 65), PSC-inflammatory bowel diseases (IBD) (78 samples from N = 41 patients), PSC without IBD (PSC, 41 samples from N = 18 patients), primary biliary cholangitis (PBC, N = 24), autoimmune hepatitis (AIH, N = 32), secondary sclerosing cholangitis (SSC, N = 12), and metabolic dysfunction-associated steatotic liver disease (MASLD, N = 24). In addition, sera after proctocolectomy were studied (44 samples/N = 10 patients). Immunofluorescent analyses were performed in tissue samples from liver, large bile duct from surgical resections, and colon of PSC patients.
Anti-αVβ6 occurred in 91% of UC, 17% of CD, 73% of PSC-IBD, 39% of PSC, 4% of PBC, 14% of AIH, and 0% of healthy controls, SSC, or MASLD. Integrin αVβ6 is selectively expressed in disease-associated epithelia of both bile duct and colon. Anti-αVβ6 levels correlate moderately with intestinal disease activity in PSC-IBD, but only weakly with biliary disease.
Anti-αVβ6 frequently occurs in patients suffering from PSC, especially in PSC-IBD. Anti-αVβ6 levels positively correlate to IBD activity in PSC-IBD, but may also occur in the absence of clinically manifest IBD in PSC.
最近，已鉴定出针对上皮粘附蛋白整合素αVβ6的自身抗体，其与溃疡性结肠炎（UC）密切相关。我们旨在阐明抗整合素αVβ6（抗αVβ6）是否存在于原发性硬化性胆管炎（PSC）、其相关的炎症性肠病或其他胆汁淤积性肝病中，以及在直肠结肠切除术后其是否持续存在。
我们在德国的两个三级中心收集的血清中，通过酶联免疫吸附测定法检测抗αVβ6，这些血清样本来自健康对照者（N = 62）、UC患者（N = 36）、克罗恩病（CD，N = 65）、PSC合并炎症性肠病（IBD）（来自41例患者的78份样本）、不合并IBD的PSC（PSC，来自18例患者的41份样本）、原发性胆汁性胆管炎（PBC，N = 24）、自身免疫性肝炎（AIH，N = 32）、继发性硬化性胆管炎（SSC，N = 12）和代谢功能障碍相关脂肪性肝病（MASLD，N = 24）。此外，还研究了直肠结肠切除术后的血清（44份样本/N = 10例患者）。对PSC患者的肝脏、手术切除的大胆管和结肠的组织样本进行免疫荧光分析。
抗αVβ6存在于91%的UC患者、17%的CD患者、73%的PSC-IBD患者、39%的PSC患者、4%的PBC患者、14%的AIH患者中，而在健康对照者、SSC患者或MASLD患者中未检出（0%）。整合素αVβ6在胆管和结肠的疾病相关上皮中选择性表达。在PSC-IBD中，抗αVβ6水平与肠道疾病活动度呈中度相关，但与胆道疾病的相关性较弱。
抗αVβ6在PSC患者中频繁出现，尤其是在PSC-IBD患者中。在PSC-IBD中，抗αVβ6水平与IBD活动度呈正相关，但在无临床明显IBD的PSC患者中也可能出现。
