Identification of Immunoglobulin G Autoantibody Against Malondialdehyde-Acetaldehyde Adducts as a Novel Serological Biomarker for Ulcerative Colitis

Michael J. Duryee, Rizwan Ahmad, Derrick D. Eichele, Carlos D. Hunter, Ananya Mitra, Geoffrey A. Talmon, Shailender Singh, Lynette M. Smith, Michael J. Rosen, Punita Dhawan, Geoffrey M. Thiele, Amar B. Singh

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION:Inflammatory bowel disease (IBD) is associated with immune responses with oxidative stress wherein high levels of malondialdehyde result in the formation of a highly stable and immunogenic malondialdehyde-acetaldehyde adduct (MAA). Thus, this study evaluated the status of MAA and anti-MAA antibody isotypes in IBD and their potential as novel serological biomarkers for differentiating ulcerative colitis (UC) from Crohn's disease (CD).METHODS:Levels of MAA and anti-MAA antibodies were examined in patients with IBD (171), non-IBD gastrointestinal diseases (77), and controls (83) from 2 independent cohorts using immunohistochemistry and enzyme-linked immunosorbent assay. Receiver operating characteristic curves and Youden cutoff index from logistic regression were used to determine the sensitivity and specificity.RESULTS:The MAA and blood immunoglobulin G (IgG) anti-MAA antibody levels were significantly elevated in IBD compared with non-IBD patients (P = 0.0008) or controls (P = 0.02). Interestingly, patients with UC showed higher levels of IgG anti-MAA (P < 0.0001) than patients with CD including those with colonic CD (P = 0.0067). The odds ratio by logistic regression analysis predicted stronger association of IgG anti-MAA antibody with UC than CD. Subsequent analysis showed that IgG anti-MAA antibody levels could accurately identify (P = 0.0004) UC in the adult cohort with a sensitivity of 75.3% and a specificity of 71.4% and an area under the curve of 0.8072 (0.7121-0.9024). The pediatric cohort also showed an area under the curve of 0.8801 (0.7988-0.9614) and precisely distinguished (P < 0.0001) UC with sensitivity (95.8%) and specificity (72.3%).DISCUSSION:Circulating IgG anti-MAA antibody levels can serve as a novel, noninvasive, and highly sensitive test to identify patients with UC and possibly differentiate them from patients with CD.

Original languageEnglish (US)
Pages (from-to)E00469
JournalClinical and translational gastroenterology
Volume13
Issue number4
DOIs
StatePublished - Apr 14 2022

ASJC Scopus subject areas

  • Gastroenterology

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