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Arthritis Rheum. 2012 Jan;64(1):99-109. doi: 10.1002/art.33396.

Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis.

Author information

1
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.

Abstract

OBJECTIVE:

Studies comparing spondylarthritis (SpA) to rheumatoid arthritis (RA) synovitis suggest that innate immune cells may play a predominant role in the pathogenesis of SpA. Recent observations have indicated a marked synovial mast cell infiltration in psoriatic SpA. We therefore undertook the present study to investigate the potential contribution of mast cells to synovial inflammation in SpA.

METHODS:

Synovial tissue and fluid were obtained from patients with either nonpsoriatic or psoriatic SpA (n=82) and patients with RA (n=50). Synovial biopsy tissue was analyzed by immunostaining and used in ex vivo cultures. Synovial fluid was analyzed by enzyme-linked immunosorbent assay.

RESULTS:

We observed a strong and specific increase of c-Kit-positive mast cells in the synovium from patients with SpA compared to the synovium from patients with RA synovitis, which was independent of disease subtype (nonpsoriatic versus psoriatic), disease duration, and treatment. Staining of mast cell granules, analysis of synovial fluid, and results in ex vivo tissue culture did not indicate increased degranulation in SpA synovitis. However, mast cells expressed significantly more interleukin-17 (IL-17) in SpA than in RA synovitis, and mast cells constituted the major IL-17-expressing cell population in the SpA synovium. Ex vivo targeting of synovial mast cells with the c-Kit inhibitor imatinib mesylate significantly decreased the production of IL-17 as well as other proinflammatory cytokines in synovial tissue cultures. Analysis of paired pre- and posttreatment synovial tissue samples indicated that the mast cell/IL-17 axis in SpA was not modulated by effective tumor necrosis factor (TNF) blockade.

CONCLUSION:

The specific and TNF-independent increase in IL-17-expressing mast cells may contribute to the progression of synovial inflammation in peripheral SpA.

PMID:
21968742
DOI:
10.1002/art.33396
[Indexed for MEDLINE]
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