IgA deficient mice develop a gluten sensitive enteropathy specifically in the ileum.

Abstract

Abstract Secretory IgA is the most abundant antibody in the intestinal mucosa 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 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 developed a line of IgA −/−mice which had never been exposed to gluten and After 8 weeks of age, challenged these mice with 10 mg of concentrated gluten or sterile water every other day for 3 weeks. We found that mice challenged with gluten developed significant shortening of their villi compared to the control. We then used high parametric flow cytometry to compare these findings to shifts in the immunological tone of the SI. Results from our experiments indicate 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.