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
Journal of Crohn's and Colitis, 2025
Pertsinidou E., Salomon B., Bergemalm D., Salihovic S., Hedin C., Ling Lundström M., Keita ?., Magnusson M., Eriksson C., Bengtson M., Grännö O., Aabrekk T., Movérare R., Rydell N., Ekoff H., Rönnelid J., Almer S., Strid H., Hjortswang H., Bresso F., Hreinsson J., Blomberg A., Carstens A., D’Amato M., Detlie T., Huppertz-Hauss G., Opheim R., Ricanek P., Kristensen V., Öhman L., Söderholm J., Kruse R., Lindqvist C., Carlson M., Repsilber D., Høivik M., Halfvarson J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Patient Stratification | Serum |  Olink Target 96 |
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.