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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
Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden; Thermo Fisher Scientific, Uppsala, Sweden.
Örebro University, School of Medical Sciences.ORCID iD: 0009-0002-8951-9839
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.ORCID iD: 0000-0002-1906-0746
Örebro University, School of Medical Sciences.ORCID iD: 0000-0001-5752-4196
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2025 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, article id jjaf062Article in journal (Refereed) Accepted
Abstract [en]

BACKGROUND AND AIMS: The diagnostic and prognostic properties of anti-integrin αvβ6 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 analysed 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 (CIs) 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<0.001) and faecal calprotectin (fcalpro) (AUC=0.88, 95%CI 0.84-0.92, P=0.09). Combining the autoantibody with fcalpro further improved diagnostic accuracy (AUC=0.97, 95%CI 0.95-0.98) and patient reclassification (P<0.001). 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=0.003).

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

Place, publisher, year, edition, pages
Oxford University Press, 2025. article id jjaf062
Keywords [en]
Autoantibodies, inflammatory bowel disease, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-120771DOI: 10.1093/ecco-jcc/jjaf062PubMedID: 40251889OAI: oai:DiVA.org:oru-120771DiVA, id: diva2:1954893
Funder
Swedish Foundation for Strategic Research, RB13- 0160Swedish Research Council, 2020-02021Region Örebro County, OLL-890291NordForsk, 90569Available from: 2025-04-28 Created: 2025-04-28 Last updated: 2025-04-28Bibliographically approved

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Salomon, BenitaBergemalm, DanielSalihovic, SamiraEriksson, CarlGrännö, OlleKruse, RobertLindqvist, Carl MårtenRepsilber, DirkHalfvarson, Jonas

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Salomon, BenitaBergemalm, DanielSalihovic, SamiraEriksson, CarlGrännö, OlleKruse, RobertLindqvist, Carl MårtenRepsilber, DirkHalfvarson, Jonas
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School of Medical SciencesÖrebro University Hospital
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