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Increased frequency of circulating IL-21 producing Th-cells in patients with granulomatosis with polyangiitis (GPA)

Abdulahad, W. H., Lepse, N., Stegeman, C. A., Huitema, M. G., Doornbos-van der Meer, B., Tadema, H., Rutgers, A., Limburg, P. C., Kallenberg, C. G. M. & Heeringa, P., 24-Jun-2013, In : Arthritis Research and Therapy. 15, 3, 12 p., 70.

Research output: Contribution to journalArticleAcademicpeer-review

INTRODUCTION: The present study aimed to explore a possible role for IL-21 producing Th-cells in the immunopathogenesis of granulomatosis with polyangiitis (GPA).

METHODS: Peripheral blood from 42 GPA patients in remission and 29 age-matched healthy controls (HCs) were stimulated in vitro, and the frequencies of IL-21 producing Th-cells were determined by flow cytometry. Since Th17-cells produce a low level of IL-21, IL-17 was also included in the analysis. Given that IL-21 is a hallmark cytokine for T follicular helper cells (T(FH)), we next evaluated the expression of their key transcription factor BCL-6 by RT-PCR and flow cytometry. To investigate the effect of IL-21 on autoantibody-production, PBMCs from GPA patients were stimulated in vitro with BAFF/IL-21 and total IgG and ANCA levels were measured in supernatants. In addition, the expression of IL-21-receptor on B-cells was analyzed.

RESULTS: Percentages of IL-21 producing Th-cells were significantly elevated in GPA-patients compared to HCs, and were restricted to ANCA-positive patients. The expression of BCL-6 was significantly higher in ANCA-positive GPA-patients, as compared with ANCA-negative patients and HCs. IL-21 enhanced the production of IgG and ANCA in vitro in stimulated PBMCs from GPA patients. No difference was found in the expression of the IL-21-receptor on B-cells between ANCA-negative patients, ANCA-positive patients, and HCs.

CONCLUSION: The increased frequency of circulating IL-21 producing Th-cells in ANCA-positive GPA patients and the stimulating capacity of IL-21 on ANCA-production suggest a role for these cells in the immunopathogenesis of GPA. Blockade of IL-21 could constitute a new therapeutic strategy for GPA.

Original languageEnglish
Article number70
Number of pages12
JournalArthritis Research and Therapy
Volume15
Issue number3
Publication statusPublished - 24-Jun-2013

    Keywords

  • SYSTEMIC-LUPUS-ERYTHEMATOSUS, ANCA-ASSOCIATED VASCULITIS, MEMORY B-CELLS, WEGENERS-GRANULOMATOSIS, DISEASE-ACTIVITY, HELPER-CELLS, DIFFERENTIATION, INTERLEUKIN-21, AUTOANTIBODIES, GENERATION

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