137: Altered Th1-Th2 response during infection is predictive for development of post-infectious Irritable Bowel Syndrome

Abstract

Aims Irritable Bowel Syndrome (IBS) is a gastrointestinal disorder with symptoms including abdominal pain, bloating and alteration of bowel habit. The causes of IBS are unknown, but due to the high incidence, IBS is becoming a burden to primary health care. Contrasting reports on immune dynamics underlying IBS development exist, and it is unclear whether there is immune activation or Th2-dominant responses in IBS individuals. Here, we performed a prospective study to investigate the involvement of the immune system in post-infectious IBS (PI-IBS) development and to characterise differences in the immune responses between IBS patients and healthy controls. Methods Blood was collected shortly after (n = 54) and one year after gastrointestinal infection (n = 143). Twenty cell subsets were analysed including CD4/CD8 T-cell subsets, γδ T-cells, B-cell subsets, DC, NK and NKT cells. Additionally, expression of IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, TNFα, TNFγ and TGFβ was quantified by qPCR in rectal biopsies taken at one year post-infection. IL1β, IL-8, TNF-α, IL-13 and IL-10 levels were also measured in the supernatant of stimulated lymphocytes using Cytometric Bead Array technique. All participants answered questionnaires at both time points and were invited for interviews to confirm their health status at one year post-infection. Results Immune phenotyping revealed elevated Th2 responses (p = 0.0283) during gastrointestinal infection in individuals that developed PI-IBS. In addition, a decrease in CD4 + IL2 + cells (p = 0.0379) correlated with a reduction in Tregs in these individuals in the initial phase. However, at one year post-infection, there was no significant difference in the systemic immune system between PI-IBS individuals and controls. Similarly, there was no sign of local immune activation in biopsies of PI-IBS individuals with ongoing symptoms. Conclusions Increased Th2 response in peripheral immune system during gastrointestinal infection represents a predisposed factor for developing post-infectious IBS. However, after the establishment of IBS, the systemic immune phenotypes normalise.