Autoantibodies against ubiquitination factor E4A (UBE4A) are associated with severity of Crohn's disease

Background: Identification of a disease- and organ-specific antoantigen can potentially contribute to understanding molecular mechanisms involved in Crohn's disease (CD) and lead to development of clinically useful markers. The aim was to identify potential intestinal autoantigens specific to patients with CID and evaluate their diagnostic value. Methods: A cDNA expression library from normal terminal ileum was created and screened with pooled sera from 3 randomly selected patients with CD. For evaluation of the diagnostic value of antibody screening, serum samples obtained from 39 patients with CD, 28 patients with ulcerative colitis (UC), and 60 healthy controls were examined for IgG against the strongest clone. Results: We identified an intestinal cDNA clone encoding ubiquitination factor E4A (UBE4A), a U-box-type ubiquitin-protein ligase. The prevalence of anti-UBE4A IgG in patients with CD was significantly higher than that in patients with UC or healthy controls (46.2% versus respectively 7.1%, P = 0.0006; 3.3%, P < 0.0001). Anti-UBE4A-positive patients with CD were more likely to require surgery (P = 0.0013). The level of anti-UBE4A IgG was correlated with disease activity (r = 0.777, P < 0.0001) and associated with stricturing or penetrating disease (P = 0.0028). Immunohistochemical studies showed upregulation of UBE4A in enteroendocrine cells of inflamed ileal mucosa with CD. Conclusions: Anti-UBE4A antibodies are potentially useful markers for detection and prediction of clinical activity and outcome in patients with CD.