Immune cell infiltration correlates with intestinal permeability, inflammation, and gastrointestinal symptoms in type 1 diabetes

免疫细胞浸润与1型糖尿病患者的肠道通透性、炎症和胃肠道症状相关

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Abstract

AIMS/INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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