Increased Proportion of TH17, TH22 and TC22 Cells and Correlations to IL-22, IL-10 and Clinical Parameters in a Cohort of Patients With Ankylosing Spondylitis From Northern Sweden.

Abstract

Background Increased levels of TH17 and TH22 as well as TC17 and TC22 cells and their related cytokines have previously been associated with ankylosing spondylitis (AS). However, the status of these inflammatory cells in a well characterized AS cohort from northern Sweden has not been studied.Objectives The aim of this study was to confirm the increased presence of inflammatory T cell subsets in peripheral blood of patients with AS and controls from northern Sweden and explore the association with clinically relevant parameters with the level of the inflammatory T cell subset(s) and related cytokines.Methods Peripheral blood mononuclear cells (PBMCs) from a cohort of 50 patients (66% men) with AS from Region Västerbotten (age 52.1±9.0 years, 100% HLA-B27+) and 50 pairwise sex- and age-matched blood donor controls (66% men, mean age 54.6±9.1 years) were stained for CD45, CD3, CD4, CD8, intracellular IL-17 and IL-22 and analyzed by flow cytometry. In addition, levels of IL-17, IL-22 and IL-10 in plasma were determined. The patients with AS were assessed for mSASSS, hsCRP, ESR, BASMI, BASFI, ASDAS-hsCRP and BASDAI.Results Pairwise comparisons of AS patients and controls showed a 1,5x to 2-fold increase of TH17, TH22 and TC22 cells among CD45+CD3+ lymphocytes in PBMCs in male patients (p=0.013, p=0.003 and p=0.024 respectively). Levels of IL-22 in plasma and proportion of TC17 correlated in male patients (Rs=0.499 p=0.003) and plasma levels of IL-10 showed an inverse correlation to TC17 in all patients (Rs=-0.276 p=0.05). In addition, male patients with ≥ 1 syndesmophyte showed significantly higher proportion of TH17 cells (p=0.038). In female AS patients there was a negative correlation between TC22 and hsCRP (Rs= -0.573, p=0.016). Conclusions We confirm an increased proportion of TH17, TH22 and TC22 cells in blood in AS male patients from northern Sweden. A positive correlation with the proinflammatory cytokine IL-22 and reverse correlation of the anti-inflammatory cytokine IL-10 in relation to TC17 corroborate the influence of these cells. In addition, a role of TH17 in the pathogenesis process is supported by the correlation between TH17 proportions and the presence of ≥ 1 syndesmophyte.