Date of Award
Spring 2023
Document Type
Open Access Thesis
Department
Biomedical Science
First Advisor
Jason Kubinak
Abstract
Secretory IgA is the most abundant antibody in the intestinal mucosal and functions as the first line of defense against pathogens and micro-organisms in the gut. Selective IgA deficiency is the most common form of antibody deficiency. Clinically, IgA deficient patients are largely asymptomatic, they are however at a higher risk of developing certain inflammatory conditions like Celiac disease; an SI-specific enteropathy triggered by exposure to dietary gluten. Interestingly, celiac patients are 10-15 times more likely to have an IgA deficiency. Recent studies have shown that IgA-/- mice develop enteropathy specifically in the ileum. We confirmed this phenotype in our IgA-/- mice and then asked the question; are IgA-/- mice sensitive to gluten? To answer this question, we singly housed IgA-/- mice on a gluten free or nutritionally matched gluten rich diet for 4 weeks and quantitatively assessed their small intestine for histopathological changes. We found that IgA-/- mice on a gluten rich diet develop a significant shortening of villi in their ileum compared to mice on a gluten free diet. Next, in order to exacerbate the phenotype, we exposed singly housed IgA-/- mice to a gluten free or gluten rich diet for 12 weeks and then used high parametric flow cytometry to compare these findings to shifts in the immunological tone of the SI. In addition, we used 16s sequencing to assess their small intestine contents for shifts in microbial ecology. Results from our experiments identify that IgA-/- mice will be a useful model for downstream studies on the mechanisms driving enhanced risk for developing gluten sensitivity in IgA-deficient humans.
Rights
© 2023, Ryan Albert William Ball
Recommended Citation
Ball, R. A.(2023). Gluten Free Diet Ameliorates SI Enteropathy in IGA Deficient Mice. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/7143