Author: Eleanor McDermid
medwireNews: The appearance of autoantibodies against integrin αvβ6 (anti-αvβ6) precedes the onset of ulcerative colitis (UC) by up to 10 years and is associated with disease severity, report researchers.
Saurabh Mehandru (Icahn School of Medicine at Mount Sinai, New York, USA) and study co-authors identified anti-αvβ6 in 12.2% of serum samples taken from 82 participants of the prospective PREDICTS cohort around 10 years before they developed UC.
The rate of autoantibody positivity increased across samples taken closer to the point of diagnosis, to 20.7% in samples taken 4 years before, 30.5% in those taken 2 years before and 52.4% in samples taken at the time of diagnosis.
By contrast, the prevalence of anti-αvβ6 was 2.7% at all timepoints in samples taken from 82 matched control participants who did not develop UC.
The researchers explain that integrin αvβ6 is thought to have an important role in maintaining epithelial barrier integrity, which led them to speculate that the loss of this integrity, potentially early in the UC disease process, would be accompanied by the appearance of anti-αvβ6.
The presence of anti-αvβ6 in samples 10 years before diagnosis was 79% accurate for distinguishing between people who did and did not develop UC, with similar results seen for positivity of later samples. And in an independent cohort (CCC-GEM Project), the team detected anti-αvβ6 in 33% of serum samples taken from 12 people around 4 years before UC diagnosis compared with 2% of 49 matched controls.
Based on these findings, the researchers believe anti-αvβ6 to have “at least as high (or higher) predictive performance” compared with existing UC biomarkers.
“The presence of anti-αvβ6 autoantibodies before UC diagnosis further suggests that a pre-clinical phase, potentially amenable to therapeutic intervention may indeed predate UC diagnosis”, they write in Gastroenterology.
They add: “The increasing prevalence of anti-αvβ6 autoantibodies with time is in contrast to other autoantibodies such as ASCA and pANCA which remain relatively stable prior to diagnosis.”
Mehandru and team then looked at the association of anti-αvβ6 with UC severity in two established UC cohorts – COMPASS (n=55) and OSCCAR (n=104).
They found that, after accounting for confounders, the presence of anti-αvβ6 was associated with a significant 24–39% increased likelihood of having more severe disease, defined by the composite of need for biologic therapy and/or systemic steroids, disease extension and hospitalisation and/or surgery.
“In contrast, pANCA, an established UC-associated biomarker, was not associated with disease outcomes”, they say.
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