TY - JOUR
T1 - Th17 expansion in granulomatosis with polyangiitis (Wegener's): the role of disease activity, immune regulation and therapy
AU - Wilde, Benjamin
AU - Thewissen, Marielle
AU - Damoiseaux, Jan
AU - Hilhorst, Marc
AU - van Paassen, Pieter
AU - Witzke, Oliver
AU - Tervaert, Jan Willem Cohen
PY - 2012
Y1 - 2012
N2 - Introduction: In autoimmune diseases, IL-17 producing T-cells (Th17), a pro-inflammatory subset of T-cells, are pathophysiologically involved. There is little knowledge on the role of Th17 cells in granulomatosis with polyangiitis (GPA). In the present study, we investigated Th17 cells, Tregs and subsets of circulating Th17 cells in GPA and related results to disease activity. Methods: 42 GPA patients in remission, 18 with active disease and 14 healthy controls (HC) were enrolled. Th17 cells, their subsets and regulatory T-cells were determined by intracellular fluorescence activated cell sorter (FACS). Data are given as mean percentage +/- SD of total T-helper-cells. Results: Th17 cells are expanded in active and quiescent GPA as compared to HC (1.7 +/- 1.4% vs. 0.7 +/- 0.3%, P = 0.006 and 1.9 +/- 1.5% vs. 0.7 +/- 0.3%, P <0.0001). Th17 expansion is stable over time and does not decline when remission is achieved. However, a negative association of Th17 cells and steroid dosage is observed (r = -0.46, P = 0.002). The Th17 expansion was not balanced by Tregs as indicated by skewed Th17/Treg ratios in active and quiescent GPA. Th17 subsets co-producing IFN gamma or IL-10 are significantly increased in GPA. GPA patients in remission not receiving maintenance therapy have significantly more IL-10/IL-17A double positive T-cells than HC (0.0501 +/- 0.031% vs. 0.0282 +/- 0.016%, P = 0.007). Conclusions: We provide evidence for a persistent, unbalanced expansion of Th17 cells and Th17 subsets which seems to be independent of disease activity. Maintenance therapy reduces -but does not normalize- Th17 expansion.
AB - Introduction: In autoimmune diseases, IL-17 producing T-cells (Th17), a pro-inflammatory subset of T-cells, are pathophysiologically involved. There is little knowledge on the role of Th17 cells in granulomatosis with polyangiitis (GPA). In the present study, we investigated Th17 cells, Tregs and subsets of circulating Th17 cells in GPA and related results to disease activity. Methods: 42 GPA patients in remission, 18 with active disease and 14 healthy controls (HC) were enrolled. Th17 cells, their subsets and regulatory T-cells were determined by intracellular fluorescence activated cell sorter (FACS). Data are given as mean percentage +/- SD of total T-helper-cells. Results: Th17 cells are expanded in active and quiescent GPA as compared to HC (1.7 +/- 1.4% vs. 0.7 +/- 0.3%, P = 0.006 and 1.9 +/- 1.5% vs. 0.7 +/- 0.3%, P <0.0001). Th17 expansion is stable over time and does not decline when remission is achieved. However, a negative association of Th17 cells and steroid dosage is observed (r = -0.46, P = 0.002). The Th17 expansion was not balanced by Tregs as indicated by skewed Th17/Treg ratios in active and quiescent GPA. Th17 subsets co-producing IFN gamma or IL-10 are significantly increased in GPA. GPA patients in remission not receiving maintenance therapy have significantly more IL-10/IL-17A double positive T-cells than HC (0.0501 +/- 0.031% vs. 0.0282 +/- 0.016%, P = 0.007). Conclusions: We provide evidence for a persistent, unbalanced expansion of Th17 cells and Th17 subsets which seems to be independent of disease activity. Maintenance therapy reduces -but does not normalize- Th17 expansion.
U2 - 10.1186/ar4066
DO - 10.1186/ar4066
M3 - Article
C2 - 23079279
SN - 1478-6354
VL - 14
SP - R227
JO - Arthritis Research & Therapy
JF - Arthritis Research & Therapy
IS - 5
ER -