Individual Variations in Anti-αvβ6 Autoantibody Levels Determined by ITGAV Gene Polymorphisms: Associations With Genetic Background and Relapse in Ulcerative Colitis

Introduction Increased expression of the epithelial-specific adhesion molecule integrin αvβ6 and the presence of anti-αvβ6 autoantibodies (V6 Ab) have been reported in ulcerative colitis (UC). However, the influence of single-nucleotide polymorphisms (SNPs) in the ITGAV gene on antibody titers, as well as their association with relapse in patients with mild disease, have not been fully elucidated. This study aimed to clarify the impact of ITGAV gene polymorphisms on serum V6 Ab levels in patients with UC. As secondary objectives, we evaluated the association between these SNPs and 1-year relapse and assessed the relapse predictive performance of V6 Ab levels using receiver operating characteristic (ROC) analysis. Methods We retrospectively analyzed 61 patients with UC whose V6 Ab levels were measured at our institution between January 2023 and June 2025. Associations between four ITGAV SNPs (rs3911238, rs3768777, rs1448427, and rs10174098) and V6 Ab levels were examined. Among 49 patients with a partial Mayo score of 0 or 1, we evaluated the relationship between SNP variants and 1-year relapse. The predictive ability of V6 Ab for relapse was assessed using ROC analysis. Results For all four ITGAV SNPs, carriers of variant alleles exhibited significantly higher serum V6 Ab levels compared with wild-type individuals. Among 49 patients with a partial Mayo score of 0 or 1, 14 (28.6%) experienced relapse within 1 year. The relapse group showed significantly higher frequencies of rs3768777, rs10174098, and rs1448427 variants than the non-relapse group. The predictive performance of V6 Ab levels for relapse yielded an area under the ROC curve of 0.78 (95% confidence interval: 0.64–0.89). At a threshold of 6.58 U/mL, sensitivity, specificity, and negative predictive value were 1.00, 0.54, and 1.00, respectively. Conclusion ITGAV gene polymorphisms determined inter-individual variation in V6 Ab levels, with variant carriers exhibiting higher antibody titers and increased risk of relapse. Low V6 Ab levels were a reliable indicator for excluding relapse. The combined use of antibody titers with ITGAV SNP information may facilitate precision stratification of patients with UC in remission or with mild disease.