P028 A distinct cellular signature of inflammatory bowel disease

Abstract

Crohn’s disease (CD), ankylosing spondylitis (AS), psoriasis (Ps) and psoriatic arthritis (PsA) are all chronic inflammatory conditions that share symptoms, and have overlapping genetic susceptibilities. The specific cellular pathways involved in disease pathogenesis have not, however, been directly compared. With a better understanding of the cell types that both cause and perpetuate these conditions, future treatments will be able to target not only the symptoms but the underlying damage that is caused in each specific disease. Following informed patient consent, peripheral blood samples were taken from CD (n = 25), AS (n = 32), Ps (n = 38), PsA (n = 30) and healthy control volunteers (n = 30). Using multi-parameter flow cytometry, we have identified 86 pre-defined cell populations including subsets of T cells, B cells, NK cells and monocytes/dendritic cells. We also performed analysis of intestinal biopsies, to examine alterations between colonic macrophage populations. We have processed 155 peripheral blood samples, from four disease groups; IBD, AS, Ps and PsA. We have uncovered numerous disease-specific variations in circulating cell populations. AS, Ps and PsA patients all have specific T-cell sub-populations that are altered compared with healthy controls. Indeed, PsA patients had approximately 55% fewer naïve and 50% more central memory CD8 T cells than healthy controls. CD showed few changes in circulating T-cell sub-populations, though total CD4 and CD8 peripheral blood T cells were increased and decreased, respectively. It is known that circulating blood monocytes infiltrate the gastrointestinal tract and their subsequent differentiation into inflammatory macrophages is essential to IBD pathogenesis. It is interesting therefore, that CD patients had more than twice the average amount of intermediate (CD14+ CD16+) monocytes in their blood than healthy controls, the only disease to show any changes in monocyte composition. Analysis of colonic biopsies has also revealed specific genes that are altered between infiltrating and mature colonic macrophages. We show clear differences in the distribution of circulating cell subsets in inflammatory conditions compared with healthy controls, including distinct differences in the immunological signatures of patients with PsA, AS, Ps, and CD.