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Th17 expansion in granulomatosis with polyangiitis (Wegener's): the role of disease activity, immune regulation and therapy

Benjamin Wilde12, Marielle Thewissen1, Jan Damoiseaux3, Marc Hilhorst1, Pieter van Paassen1, Oliver Witzke2 and Jan Willem Cohen Tervaert13*

Author Affiliations

1 Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht, PO Box 5800, Maastricht, 6202 AZ, The Netherlands

2 Department of Nephrology, University Duisburg-Essen, Hufelandstr. 55, Essen, 45127, Germany

3 Laboratory of Clinical Immunology, Maastricht University Medical Center, PO Box 5800, Maastricht, 6202 AZ, The Netherlands

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Arthritis Research & Therapy 2012, 14:R227  doi:10.1186/ar4066

Published: 18 October 2012



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.


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.


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 IFNγ 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).


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.