Distinct Adaptive Immunophenotypes in duodenal mucosa but not in peripheral blood of patients with functional dyspepsia

Background and aimsFunctional dyspepsia is characterised by chronic symptoms of post- prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cell have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific immunophenotype was associated with FD. This study aimed to characterise immune populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology.MethodsWe identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry. We also analysed duodenal eosinophils and T cell populations in peripheral blood from 37 controls and 49 patients and investigated if subtyping patients based on reported symptoms or co-morbidity identified specific immunophenoptypes.ResultsIn addition to increased duodenal mucosal CD4+ effector cells, FD patients demonstrated a shift in the T helper cell balance compared to controls. Patients had increased duodenal mucosal Th2 populations in the effector (13.03±16.11, 19.84±15.51, p=0.038), central memory (23.75±18.97, 37.52±17.51, p=0.007) and effector memory (9.80±10.50 vs 20.53±14.15, p=0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, p=0.03) and effector memory (11.95±8.42 vs 18.44±15.63, p=0.027) subsets.ConclusionOur findings confirm the involvement of adaptive responses in the aetiopathogenesis of FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.