Understanding the Role of Malondialdehyde-Acetaldehyde Adducts (MAA) in Inflammatory Bowel Disease

Author

Megan L. Otte, University of Nebraska Medical CenterFollow

ORCID ID

0000-0003-2984-8198

Graduation Date

Summer 8-9-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Immunology, Pathology & Infectious Disease

First Advisor

Amar Singh

Abstract

Inflammatory Bowel Disease (IBD) comprises autoimmune diseases of the gastrointestinal tract that greatly reduce the quality of life of patients and currently afflict up to 200 individuals per 100,000 Americans. Ulcerative colitis (UC) and Crohn’s Disease (CD), the two principal diseases comprising IBD, share symptoms and risk factors, however, precise etiology remains unclear. The diagnostics and clinical management of IBD have progressed greatly in recent years especially due to immune modulating therapies and biologics, however, IBD and its specific forms are still difficult to diagnose and cannot be cured with current treatments. The overarching mechanisms of IBD pathogenesis are known to include dysregulation of the gut barrier, the gut microbiome, and inflammatory cytokine pathways, however, the methods by which specific cells, proteins, and signals interact to drive IBD development remain poorly understood. The aim of this study was to understand the role of Malondialdehyde-acetaldehyde adducts (MAA), a biomarker of IBD, on the disease process. Results using exogenous administration of anti-MAA IgG in a murine model of infection-induced colitis were not conclusive. However, studies where cultured intestinal epithelial cells were exposed to MAA antigen showed dysregulations of the tight junction and extracellular matrix (ECM)-related proteins. In further studies using a murine model of colitis and recovery, exogenous administration of MAA antigen inhibited colitis-induced tissue damage and promoted recovery. Overall, these studies suggested a causal association between MAA and ulcerative colitis, however, further in-depth studies are needed for delineation of the precise role MAA plays in IBD.

Comments

2024 Copyright, the authors

Recommended Citation

Otte, Megan L., "Understanding the Role of Malondialdehyde-Acetaldehyde Adducts (MAA) in Inflammatory Bowel Disease" (2024). Theses & Dissertations. 847.
https://digitalcommons.unmc.edu/etd/847