Differences in Anti-αvβ6 Integrin Antibody Expression between U.S. and Japanese Cohorts in Inflammatory Bowel Disease

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BACKGROUND: Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), have complex pathologies requiring precise diagnostic tools. We evaluated the clinical utility of anti-integrin αvβ6 antibodies in diagnosing UC, focusing on differences between a U.S. cohort (self-reported White) and a Japanese cohort, and additionally assessed whether combining anti-αvβ6 with anti-EPCR improved diagnostic performance. METHODS: Serum anti-αvβ6 antibody levels were measured in 1138 participants (514 in the U.S. cohort, 624 in the Japanese cohort), including 1093 IBD cases and 45 healthy control subjects. Positivity rates and titers were compared between cohorts, and associations with clinical subphenotypes and anti-EPCR were examined. RESULTS: Anti-αvβ6 positivity was significantly higher in UC patients (85.4%) than in CD patients (16.4%) or control subjects (0%). Within UC, high positivity was observed across all disease extents, with only minor cohort differences. Longer disease duration was associated with lower positivity in both cohorts. In CD, the U.S. cohort showed higher positivity (23.4%) than the Japanese cohort (10.1%), particularly in colonic CD. Absence of ileal involvement, strictures, or perianal disease was associated with higher positivity. Anti-αvβ6 and anti-EPCR levels were strongly correlated, but their expression patterns differed in primary sclerosing cholangitis-associated IBD. Combining anti-αvβ6 and anti-EPCR improved UC diagnostic accuracy (area under the curve, 0.98; 95% confidence interval, 0.95-1.00) over either antibody alone (P = .00264). CONCLUSIONS: Anti-αvβ6 is a valuable biomarker for UC diagnosis. However, this study demonstrated differences in its behavior between U.S. and Japanese cohorts, particularly in CD. Cohort-informed interpretation and combined antibody testing may improve diagnostic precision and disease stratification in IBD.

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