抗整合素αvβ6 IgG抗体作为溃疡性结肠炎的诊断和预后标志物:一项确定特定疾病表型的横断面和纵向研究

Eleftheria Pertsinidou, Benita Salomon, Daniel Bergemalm, Samira Salihovic, Charlotte R H Hedin, Maria Ling Lundström, Åsa V Keita, Maria K Magnusson, Carl Eriksson, May-Bente Bengtson, Olle Grännö, Tone B Aabrekk, Robert Movérare, Niclas Rydell, Helena Ekoff, Johan Rönnelid, Mauro D'Amato, Trond E Detlie, Gert Huppertz-Hauss, Randi Opheim, Petr Ricanek, Vendel A Kristensen, Lena Öhman, Johan D Söderholm, Robert Kruse, Carl M Lindqvist, Marie Carlson, Dirk Repsilber, Marte L Høivik, Jonas Halfvarson
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引用次数: 0

摘要

背景与目的:抗整合素αvβ6 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。我们的目的是评估抗整合素αvβ6自身抗体的诊断性能,并检查其与疾病结局的关系。方法:采用基于EliA™技术的内部荧光酶免疫分析法,对来自瑞典一组疑似炎症性肠病(IBD, n=473)患者的血清样本进行分析。研究结果在挪威基于人群的初始队列(n=570)中得到验证。通过计算曲线下面积(AUC)和95%置信区间(CIs)来评估诊断效果,并确定敏感性和特异性。用净重分类指数评价重分类。结果:在发现队列中,UC、ibd未分类或结肠克罗恩病患者与有症状和健康对照者相比,表现出更高的中位自身抗体水平。在验证队列中,自身抗体对UC的敏感性为79%,特异性为94%,临界值为400 UA/l。其诊断效能(AUC=0.92, 95%CI 0.89-0.95)优于hs-CRP (AUC=0.65, 95%CI 0.60-0.70)。结论:抗整合素αvβ6是UC可靠的诊断和预后指标,具有临床应用价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti-integrin αvβ6 IgG antibody as a diagnostic and prognostic marker in ulcerative colitis: A cross-sectional and longitudinal study defining a specific disease phenotype.

Background and aims: 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.

Methods: 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.

Results: 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).

Conclusions: Anti-integrin αvβ6 is a reliable diagnostic and prognostic marker for UC, with potential clinical implementation.

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