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

J Crohns Colitis. 2025 May 8;19(5):jjaf062. doi: 10.1093/ecco-jcc/jjaf062.

Abstract

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.

Keywords: autoantibodies; inflammatory bowel disease; ulcerative colitis.

MeSH terms

  • Adult
  • Antigens, Neoplasm
  • Autoantibodies* / blood
  • Biomarkers / blood
  • Colitis, Ulcerative* / blood
  • Colitis, Ulcerative* / diagnosis
  • Colitis, Ulcerative* / immunology
  • Crohn Disease / blood
  • Crohn Disease / diagnosis
  • Crohn Disease / immunology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunoglobulin G* / blood
  • Integrins* / immunology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • Sensitivity and Specificity
  • Sweden

Substances

  • Biomarkers
  • Autoantibodies
  • Integrins
  • integrin alphavbeta6
  • Immunoglobulin G
  • Antigens, Neoplasm