Loss of enteroendocrine cells in autoimmune-polyendocrine-candidiasis-ectodermal-dystrophy (APECED) syndrome with gastrointestinal dysfunction

Abstract

Background: Enteroendocrine (EE) cells are necessary for the regulation of gastrointestinal function. The lack of intestinal enteroendocrine cells in enteroendocrine cell dysgenesis causes severe malabsorptive diarrhea. Autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is often accompanied by gastrointestinal (GI) symptoms.

Aims: We hypothesized that an autoimmune attack against the cells of the GI-associated diffuse endocrine system may be a specific feature of GI dysfunction in APECED disorders.

Methods: Biopsies were obtained during routine diagnostic endoscopy from 35 pediatric patients with gastrointestinal symptoms as well as from five healthy controls; biopsies were immunostained for chromogranin A and serotonin. Four patients were classified as APECED syndrome on molecular and clinical grounds.

Results: Immunohistological analysis of biopsies along the GI tract (stomach, duodenum, colon) immunostained with chromogranin A and serotonin revealed a widespread reduction or complete loss of EE cells in all four patients with APECED syndrome suffering from severe diarrhea, vomiting, malabsorption, or constipation. In contrast, EE cells were present in pediatric patients with similar gastrointestinal symptoms caused by inflammatory bowel disease, celiac disease, lymphocytic colitis, and autoimmune disorders without endocrinopathy or graft vs. host disease of the gut.

Conclusions: The reduction of EE cells is a specific and important early event in the pathogenesis of APECED with GI dysfunction. We propose a diagnostic algorithm integrating clinics, genetics and immunohistology.