Immune cell infiltration correlates with intestinal permeability, inflammation, and gastrointestinal symptoms in type...

Our study explores interconnections between the occurrence of gastrointestinal (GI) symptoms with immunohistochemical analysis of colon biopsies, markers of intestinal permeability, and inflammation in individuals with type 1 diabetes.

Twenty subjects with type 1 diabetes and seven healthy controls underwent colonoscopy. Colon biopsy materials were analyzed immunohistochemically for CD3+, CD20+, CD4+, CD8+, CD138+, and CD68+ cell counts. The levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), and endogenous anti-endotoxin core antibodies (EndoCAb IgG and IgM) were measured in serum. Fecal calprotectin, immunoglobulin A (IgA), albumin, protein, and intestinal alkaline phosphatase (IAP) activity were analyzed in patient subgroups.

Immune cell infiltration in lamina propria did not differ between type 1 diabetes and control subjects. In type 1 diabetes, the number of CD20+, CD8+, CD138+, and CD68+ cells correlated with several GI symptoms and usage of medications for diarrhea. Fecal calprotectin correlated positively with the number of CD20+ B cells, CD3+ T cells, and CD138+ plasma cells. A negative correlation was found between CD20+ B-cell number and fecal IgA, while CD68+ macrophage number correlated positively with fecal albumin. Serum EndoCAb IgM correlated negatively with CD138+ plasma cells and CD4+ T cells, and positively with CD68+ macrophages. Serum LBP correlated negatively with CD4+ T cells, demonstrating links between gut mucosal inflammation and the systemic response to endotoxin.

In type 1 diabetes, CD immune cell infiltration in the colon mucosa tended to correlate with fecal and systemic markers of inflammation and gastrointestinal symptoms. A key direction for future studies will be to elucidate the underlying pathogenic mechanisms.