# Characteristics of anti–integrin αvβ6 autoantibodies in patients with ulcerative colitis

## TL;DR

Researchers found shared antibody features in ulcerative colitis patients that target a specific protein, which could help explain the disease's cause.

## Contribution

Identified shared antibody sequences in UC patients targeting integrin αvβ6, suggesting a common mechanism in disease pathogenesis.

## Key findings

- Two shared heavy chain CDR3 amino acid sequences were found in anti–integrin αvβ6 autoantibodies from UC patients.
- Some antibodies contained RGD sequences mimicking integrin ligand recognition and blocked fibronectin binding.
- Cross-reactivity with integrin αvβ3 was observed in some monoclonal antibodies.

## Abstract

Ulcerative colitis (UC) is a chronic inflammatory condition of the colon that primarily affects the mucosal layer. Previously, we identified autoantibodies against integrin αvβ6 in patients with UC. In this study, we established monoclonal antibodies (mAbs) from patients with UC to reveal the features and functions of these anti–integrin αvβ6 autoantibodies. We identified two shared heavy chain complementarity-determining region 3 (CDR3) amino acid sequences among different patients with UC. Notably, several mAbs contained the RGD sequence in their heavy chain CDR3 that mimicked the key recognition sequence of integrin αvβ6 ligands such as fibronectin. Almost all mAbs selectively reacted with integrin αvβ6 in the presence of divalent cations (Ca2+ and Mg2+) and blocked fibronectin–integrin αvβ6 binding. MAbs that shared the same heavy chain CDR3 amino acid sequence showed differences in reactivity to integrin αvβ6, indicating that the reactivity of these mAbs is also affected by the light chain. Some of the mAbs showed varying degrees of cross-reactivity with integrin αvβ3. The identification of shared CDR3 amino acid sequences in anti–integrin αvβ6 antibodies from several patients with UC suggests a common mechanism underlying their production, which may help elucidate the pathogenesis of UC.

Common amino acid sequences in the heavy-chain CDR3 are shared among anti-integrin avb6 autoantibodies of patients with UC.