Regulatory T Cell Subsets In Australian And Malaysian Adults With Inflammatory Bowel Disease

Abstract

A rise in the incidence and prevalence of inflammatory bowel disease (IBD) has been noted as nations become more developed. Once considered a disease exclusive to the West, IBD, which encompasses Crohn’s disease (CD) and ulcerative colitis (UC), is being seen more frequently in rapidly-developing Asian countries. This study sought to compare immune parameters in Australian and Malaysian patients with inflammatory bowel disease. IBD as well as control subjects were recruited from the Concord Repatriation General Hospital (CRGH) in Sydney, Australia; this was followed by recruitment of subjects from the University of Malaya Medical Centre (UMMC) in Kuala Lumpur, Malaysia. Blood and colonic mucosal samples for subjects from both sites were obtained, as were clinical details. Multi-parameter flow cytometric panels were developed to enable analysis of regulatory and conventional T cell frequencies in blood and mucosa, as well as expression of various IBD-related T cell homing receptors/transcription factors. A total of 111 subjects were recruited. Of these, 64 were male and 47 were female. A total of 58 subjects were recruited from CRGH (29 with CD, 12 with UC and 17 control subjects); among these there were 36 male and 22 female subjects. Of the CRGH subjects, 31 were Caucasian and 27 were of Asian descent. The mean Harvey-Bradshaw Index (HBI) score for CD patients was 3.5±4.0, indicating that the patients were in remission; whilst the mean Partial Mayo score for the UC subjects recruited from CRGH was 4.8±6.2, indicating that these patients had mild-to-moderate disease activity. Of the 53 subjects recruited from UMMC, 21 were CD patients and 23 had UC. There were 9 control subjects. There were 28 male and 25 female subjects from UMMC, where 10 were ethnic Malays, 21 ethnic Chinese, 21 ethnic Indians and 1 subject who was of Middle-Eastern descent. The mean HBI score for Malaysian CD patients was 3.7±2.7, indicating that these patients were in remission. Mean Partial Mayo score for the UMMC UC subjects was 1.7±1.0, indicating that the UC patients were in remission as well. Based on clinical information however, patients from Malaysia had more severe disease at time of recruitment as compared to those in Australia. Overall, no significant difference was noted when the percentage of Tregs in the PBMC of controls vs subjects with IBD was compared, either between controls and pooled IBD patients or between controls and patients with CD or UC. Australian vs. Malaysian subjects showed differences between total Treg cells and Treg subsets (as well as total CD4 T cells and Tconv subsets) within PBMCs. Mean Treg as well as Tconv frequency differed between control subjects from the two countries. Mean effector/memory Tconv frequency in the peripheral blood also differed for CD and UC patients from Australia vs. Malaysia. Effector/memory as well as naive Treg frequencies in the mucosa of patients with inactive IBD were different from controls. The differences in regulatory T cell frequencies as well as subset populations may explain differences in clinical presentation of IBD amongst Asian patients. However, these differences may also be due to an increased awareness of such conditions, as well as proper optimisation of initial treatment regimes, within Australia as compared to Malaysia.