Tryptophan Hydroxylase Autoantibodies (TPHAbs) in Autoimmune Polyendocrine Syndrome Type 1 (APS1): An Immunohistochemical Study
R Alaggio, R Scarpa, J Furmaniak, S Chen, B Rees Smith, L Morlin, S Masiero, L Norberto, C Betterle. University of Padua, Padua, Italy; FIRS Laboratories, Cardiff, United Kingdom
Background: APS1 is a rare hereditary disorder characterized by autoimmune manifestations involving endocrine and non-endocrine tissues. Recently, TPHAbs direct against serotonin-producing enterochromaffin cells (EC) have been found in a subset of patients in association with gastrointestinal dysfunction (GID).
Design: The aim of the study was to investigate the relationship between morphologic alterations in gastrointestinal tract and clinical features in TPHAbs positive patients (TPHAbs+). Serum TPHAbs were measured in 60 APS1 patients. Thirteen out of 36 TPHAbs+ (5 with and 8 without GID) undewent gastroduodenal endoscopy with gastric (antrum and body) and duodenal biopsies. In 2 cases colonic biopsies were also available. Bioptic specimens from 2 TPHAbs negative APS1 patients (TPHAbs-) and 6 healthy patients were used as controls. HE stained sections were evaluated. Immunoistains to study endocrine cells [Serotonin, Chromogranin A (CGA), Gastrin] and inflammatory infiltrate (CD3, CD4, CD8, CD20) were performed.
Results: Histology revealed a mild to moderate lympho-plasmacytic infiltrate in both antrum and body within the lamina propria in the 13 TPHAbs+ with increased CD3+/CD8+ intraepithelial lymphocytes (IELs). Eight duodenal biopsies, respectively from 4 patients with GID (80%) and 4 asymptomatic (50%), showed a significant infiltrate with increased IELs. Focal atrophy of oxyntic mucosa was seen in 4 cases (31%), intestinal metaplasia in 6 (46%). EC-like hyperplasia was absent. Serotonin immunostaining showed no EC in 12 antral, 11 body and 5 duodenal biopsies. Interestingly duodenum from 4/5 patients with GID lacked EC, with only 2 positive cells in the remaining case. Colonic samples displayed both inflammatory infiltrate and paucity of EC. Gastrin was negative in 5 antral and 7 duodenal samples. CGA+ cells were absent in 5 antral, 5 body and 2 duodenal biopsies, in keeping with reduction of enteroendocrine cells. Controls lacked inflammatory infiltrate and alterations of endocrine cells.
Conclusions: TPHAbs in APS1 patients are associated with a peculiar morphologic pattern of autoimmune gastritis, with involvement of antrum and diffuse disruption of EC. The extension of the process to the duodenum and colon is associated with clinical symptoms.
Monday, March 22, 2010 1:00 PM
Poster Session II # 83, Monday Afternoon