Characteristics of anti-integrin αᵥβ₆ autoantibodies in patients with ulcerative colitis

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.