Pertsinidou Eleftheria, Salomon Benita, Bergemalm Daniel, Salihovic Samira, Hedin Charlotte R H, Ling Lundström Maria, Keita Åsa V, Magnusson Maria K, Eriksson Carl, Bengtson May-Bente, Grännö Olle, Aabrekk Tone B, Movérare Robert, Rydell Niclas, Ekoff Helena, Rönnelid Johan, D'Amato Mauro, Detlie Trond E, Huppertz-Hauss Gert, Opheim Randi, Ricanek Petr, Kristensen Vendel A, Öhman Lena, Söderholm Johan D, Kruse Robert, Lindqvist Carl M, Carlson Marie, Repsilber Dirk, Høivik Marte L, Halfvarson Jonas
Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
Thermo Fisher Scientific, Uppsala, Sweden.
J Crohns Colitis. 2025 May 8;19(5). doi: 10.1093/ecco-jcc/jjaf062.
The diagnostic and prognostic properties of anti-integrin αvβ6 immunoglobulin G (IgG) autoantibodies in ulcerative colitis (UC) are poorly understood. We aimed to assess the diagnostic performance of anti-integrin αvβ6 autoantibodies and examine their association with disease outcomes.
Serum samples from a Swedish inception cohort of patients with suspected inflammatory bowel disease (IBD, n = 473) were analyzed using an in-house fluorescence enzyme immunoassay based on EliA technology. Findings were validated in a Norwegian population-based inception cohort (n = 570). Diagnostic performance was assessed by calculating the area under the curve (AUC) with 95% confidence intervals and determining sensitivity and specificity. Reclassification was evaluated using the net reclassification index.
In the discovery cohort, patients with UC, IBD-unclassified, or colonic Crohn's disease exhibited higher median autoantibody levels compared to symptomatic and healthy controls. In the validation cohort, the autoantibody demonstrated 79% sensitivity and 94% specificity for UC vs symptomatic controls at a cut-off of 400 UA/l. Its diagnostic performance (AUC = 0.92, 95% CI, 0.89-0.95) was superior to hs-CRP (AUC = 0.65, 95% CI, 0.60-0.70, P < .001) and faecal calprotectin (fcalpro) (AUC = 0.88, 95% CI, 0.84-0.92, P = .09). Combining the autoantibody with fcalpro further improved diagnostic accuracy (AUC = 0.97, 95% CI, 0.95-0.98) and patient reclassification (P < .001). Autoantibody positivity was associated with a severe phenotype of UC, characterised by increased inflammatory activity and higher IL-17A and granzyme B levels. Higher autoantibody levels were linked to an aggressive disease course, remaining stable in aggressive UC but decreasing in indolent disease (P = .003).
Anti-integrin αvβ6 is a reliable diagnostic and prognostic marker for UC, with potential clinical implementation.
抗整合素αvβ6免疫球蛋白G（IgG）自身抗体在溃疡性结肠炎（UC）中的诊断和预后特性尚不清楚。我们旨在评估抗整合素αvβ6自身抗体的诊断性能，并研究其与疾病结局的关联。
使用基于EliA技术的内部荧光酶免疫分析法，对瑞典一个疑似炎症性肠病（IBD，n = 473）起始队列患者的血清样本进行分析。研究结果在挪威一个基于人群的起始队列（n = 570）中得到验证。通过计算曲线下面积（AUC）及其95%置信区间，并确定敏感性和特异性来评估诊断性能。使用净重新分类指数评估重新分类情况。
在发现队列中，与有症状的对照组和健康对照组相比，UC、未分类的IBD或结肠克罗恩病患者的自身抗体水平中位数更高。在验证队列中，当临界值为400 UA/l时，该自身抗体对UC与有症状对照组的敏感性为79%，特异性为94%。其诊断性能（AUC = 0.92，95% CI，0.89 - 0.95）优于高敏C反应蛋白（hs-CRP，AUC = 0.65，95% CI，0.60 - 0.70，P <.001）和粪便钙卫蛋白（fcalpro，AUC = 0.88，95% CI，0.84 - 0.92，P =.09）。将该自身抗体与fcalpro联合使用可进一步提高诊断准确性（AUC = 0.97，95% CI，0.95 - 0.98）和患者重新分类情况（P <.001）。自身抗体阳性与UC的严重表型相关，其特征为炎症活动增加以及白细胞介素-17A和颗粒酶B水平升高。较高的自身抗体水平与侵袭性疾病病程相关，在侵袭性UC中保持稳定，但在惰性疾病中降低（P =.003）。
抗整合素αvβ6是UC可靠的诊断和预后标志物，具有潜在的临床应用价值。
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