Journal
RHEUMATOLOGY
Volume 53, Issue 4, Pages 621-630Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/ket406
Keywords
granulomatosis with polyangiitis (GPA); follicular helper T (TFH); regulatory T (Treg) cells; B cell depletion
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Funding
- St Thomas' Wegener's Trust
- St Thomas' Lupus Trust
- Crohn's in Childhood Research Association
- Diabetes UK
- Medical Research Council [MR/J006742/1] Funding Source: researchfish
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Methods. The frequencies of circulating T follicular helper cells (cTFHs) and regulatory T cells (Tregs) from 36 GPA patients including 11 rituximab-treated patients and 10 healthy controls were studied by flow cytometry. The functional capacity of Tregs was assessed by in vitro co-culture assays. Results. We observed an increased frequency of cTFHs and a reduced frequency of antigen-experienced Tregs in peripheral blood from GPA patients on conventional therapies but not in those treated with rituximab compared with healthy controls. Furthermore, the ratio of cTFHs to Tregs was significantly higher in GPA patients on conventional therapies than in GPA patients treated with rituximab who were clinically improved or controls. Whereas Tregs were numerically reduced in GPA patients on conventional therapy, the suppressive capacity of Tregs on a per cell basis was not significantly altered in these individuals. Conclusion. Our study illustrated increased cTFHs with decreased antigen-experienced Tregs in GPA patients on conventional therapies, but in B cell-depleted patients the levels of cTFHs and Tregs were similar to healthy controls. The negative correlation between cTFHs and Tregs implies the balance between T cell subsets and its B cell dependence impact on disease activity in GPA.
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