293 Increased Intraepithelial Lymphocytes and Mast Cells with Depressed Serotonin Transporter in Duodenal Biopsies and Platelets of Patients with IBS and Diarrhoea (IBS-D): Correlation with Bowel Frequency

Abstract

INTRODUCTION: Several groups report increased mucosal inflammation and increased circulating cytokines, which both cell and animal studies show to depress SERT, in IBS. We therefore assessed mucosal and platelet SERT function together with 5HT & Mast Cell tryptase release (MCT) from duodenal biopsies which were also assessed for mast cells (MC), intra-epithelial lymphocytes (IEL) & 5HT-containing enterochromaffin cells (EC) compared to coeliac patients who are known to have mucosal inflammation with depressed SERT mRNA. AIMS & METHODS: 28 healthy volunteers, 20 patients with IBS-D & 20 with untreated coeliac disease (CD) completed bowel symptom questionnaires and underwent duodenal biopsy. 5HT & MCT release was assayed after 6 hour incubation. MC, IELs & ECs were identified by immuno-histochemistry. SERT and cytokeratin 20(CK20) mRNA were assessed by Taqman qRT-PCR. Platelet SERT function was assayed by H3-5HT uptake. Project supported by Novartis Pharma AG. RESULTS: IBS-D showed increase IELs, mast cell numbers and increased mast cell tryptase release (see Table). DIBS also showed depressed SERT/CK20(arbitrary units) at 0.19(0.1-0.43) versus 0.96(0.14-1.40) for HV, p<0.02. Platelet uptake of H3-5HT was also depressed at 12.8(8.3-23.2) versus 45.2(27.7-69.3)pmol/min/ mg protein for HV, p<0.01. CD had intermediate values, difference NS v HV. Mast cell numbers correlated (r=0.56, p=0.02) with stool frequency in IBS patients but not in coeliacs nor HV. IELs, in HV and IBS, correlated positively with mast cell numbers r=0.45 , p=0.001 and with EC count r=0.39, p=0.006 but negatively with SERT r=-0.37 ,p=0.01 and platelet 5HT uptake -0.53, p=0.001. CONCLUSIONS: IBS-D is characterised by increased duodenal IELs and mast cells associated with increased mast cell tryptase release. The depressed SERT in mucosa and platelets correlates with mucosal IELs and may be secondary to increased inflammatory mediators. Depressed SERT may contribute to increased 5HT availability and diarrhoeal symptoms. Mast cell numbers correlate with stool frequency suggesting mast cell products also play a part in symptoms.