Editorial: Anti-Integrin αvβ6 Autoantibodies for Distinguishing Ulcerative Colitis From Crohn's Disease

Abstract

Distinguishing ulcerative colitis (UC) from Crohn's disease (CD) depends on the combined interpretation of clinical, endoscopic and histological findings. Serological markers such as ANCA and ASCA are used as adjuncts, but their accuracy in separating UC from CD is limited [1]. Anti-integrin αvβ6 autoantibodies were first reported in UC in 2021 [2]. Subsequent studies have confirmed their diagnostic value in independent cohorts [3-5], and anti-integrin αvβ6 autoantibodies have also been detected before the diagnosis of UC [6]. In this issue of Alimentary Pharmacology & Therapeutics, Truniger et al. prospectively studied 224 patients with established UC or CD [7].

Anti-integrin αvβ6 autoantibodies had an AUC of 0.897 (sensitivity 85.8%, specificity 87.1%), compared with 0.736 for the p/aANCA-positive/ASCA IgG-negative profile and 0.704 for the p/aANCA-positive/ASCA IgA-negative profile [7]. In this first direct comparison using the same serum samples, adding conventional ANCA/ASCA profiles provided little additional diagnostic information beyond anti-integrin αvβ6 autoantibodies, indicating that anti-integrin αvβ6 is a better serological discriminator between UC and CD than conventional testing.

The findings within CD are also informative. Positivity was 7.9% in ileal CD and 8.1% in ileocolonic CD, but 43.8% in colonic CD [7]. Because colonic CD is the phenotype in which separation from UC can be particularly difficult [8], this relatively high positivity may reduce the discriminatory value of anti-integrin αvβ6 in the subgroup in which it would be most clinically useful. It may also have biological implications, as integrin αvβ6 is induced in injured epithelium and contributes to transforming growth factor-β activation during mucosal repair [2]. The higher positivity in colonic CD may therefore reflect a shared colonic inflammatory pathway rather than simply false-positive results. Whether this has biological significance remains uncertain.

Whether anti-integrin αvβ6 autoantibodies are useful when the diagnosis is uncertain remains to be determined. In the present study, all patients had an established diagnosis of UC or CD, and those with indeterminate colitis were excluded. The performance of the assay in newly presenting patients, particularly those with colon-limited or unclassified disease, remains an important question.

In a direct, same-sample comparison, Truniger et al. show that anti-integrin αvβ6 autoantibodies are a better serological discriminator than ANCA and ASCA in established UC and CD. Whether this advantage extends to the diagnostically uncertain cases where it would be most valuable is the question that now warrants prospective study.

Yuya Muramoto: conceptualization, writing – original draft, writing – review and editing. Takeshi Kuwada: writing – review and editing, supervision. Masahiro Shiokawa: supervision, writing – review and editing.

The authors have nothing to report.

M.S. received a research grant from Medical and Biological Laboratories Co. Ltd. M.S. and T.K. are inventors on a patent licensed to Medical and Biological Laboratories Co. Ltd. Y.M. declares no conflicts of interest.

This article is linked to Truniger et al. papers. To view these articles visit https://doi.org.10.1111/apt.70926 and https://doi.org.10.1111/apt.71002.

Data sharing is not applicable to this article as no new data were created or analysed in this study.