PMID- 18069675 OWN - NLM STAT- MEDLINE DCOM- 20080515 LR - 20180913 IS - 1078-0998 (Print) IS - 1078-0998 (Linking) VI - 14 IP - 3 DP - 2008 Mar TI - Autoantibodies against ubiquitination factor E4A (UBE4A) are associated with severity of Crohn's disease. PG - 310-7 AB - BACKGROUND: Identification of a disease- and organ-specific autoantigen 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 CD 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. FAU - Sakiyama, Toshio AU - Sakiyama T AD - Department of Digestive and Life-style Related Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. sakiyama@po.synapse.ne.jp FAU - Fujita, Hiroshi AU - Fujita H FAU - Tsubouchi, Hirohito AU - Tsubouchi H LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Inflamm Bowel Dis JT - Inflammatory bowel diseases JID - 9508162 RN - 0 (Antibodies, Anti-Idiotypic) RN - 0 (Autoantibodies) RN - 0 (Biomarkers) RN - 0 (DNA, Complementary) RN - 0 (Immunoglobulin G) RN - EC 2.3.2.27 (UBE4A protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Adult MH - Antibodies, Anti-Idiotypic/immunology MH - Autoantibodies/*immunology MH - Biomarkers/metabolism MH - Crohn Disease/*immunology/metabolism/pathology MH - DNA, Complementary/*genetics MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - *Gene Expression MH - Humans MH - Ileum/immunology/pathology MH - Immunoglobulin G/immunology MH - Immunohistochemistry MH - Intestinal Mucosa/immunology/pathology MH - Male MH - Polymerase Chain Reaction MH - Severity of Illness Index MH - Ubiquitin-Protein Ligases/biosynthesis/*genetics/*immunology EDAT- 2007/12/12 09:00 MHDA- 2008/05/16 09:00 CRDT- 2007/12/12 09:00 PHST- 2007/12/12 09:00 [pubmed] PHST- 2008/05/16 09:00 [medline] PHST- 2007/12/12 09:00 [entrez] AID - 10.1002/ibd.20328 [doi] PST - ppublish SO - Inflamm Bowel Dis. 2008 Mar;14(3):310-7. doi: 10.1002/ibd.20328.