Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Mast Cells Contribute to Synovial Inflammation in Non-Psoriatic and Psoriatic Spondyloarthritis.
Noordenbos1, Troy, Yeremenko1, Nataliya, Cantaert1, Tineke, Teitsma1, Christine, van de Sande1, Marleen, Tak1, Paul P., Canete2, Juan
We recently observed a striking synovial infiltration with cells positive for C-kit, a marker for mast cells, in psoriatic arthritis (PsA). As mast cells have potent inflammatory functions, including the production of pro-inflammatory cytokines, we performed a systematic analysis of mast cells infiltration in different forms of chronic inflammatory arthritis.
Materials and Methods:
Synovial tissue biopsies from active rheumatoid arthritis (RA)(n=21), non-psoriatic spondyloarthritis (SpA)(n=16), and PsA (n=23) was stained by immunohistochemistry and double immunofluorescence. Synovial fluid (SF) from RA (n=18), SpA (n=19), and PsA (n=16) was analyzed by ImmunoCap and ELISA. The effect of C-kit inhibition by imatinib mesylate on proinflammatory cytokine production was tested in vitro on fresh SpA synovial biopsies.
C-kit positive mononuclear cells were found in the synovial sublining in all disease groups. Double stainings with tryptase confirmed that C-kit indeed identified mast cells. C-kit positive mast cells were significantly increased in SpA (p=0.010) and PsA (p=0.001) versus RA despite similar levels of global inflammation as reflected by CD3, CD20, and CD68 staining. This was confirmed in an independent cohort of early untreated SpA and RA. The synovial infiltration by mast cells was not purely inflammation-driven as it persisted in SpA synovial biopsies taken after 12 weeks of successful treatment with TNF blockers. SF levels of factors involved in chemotaxis and differentiation of mast cells such as SCF, IL-3, and IL-33 were similar in all groups but sST2, the soluble decoy receptor for IL-33, was significantly decreased in SpA. As to the function of mast cells in synovial inflammation, double staining of the c-kit positive cells with toluidine blue and anti-tryptase and SF analysis for mast cell products did not show evidence for enhanced degranulation in SpA versus RA synovitis. Preliminary data, however, show IL-17 signal in the synovial mast cells. Accordingly, C-kit inhibition in ex-vivo synovial cultures strongly reduced the production and secretion of pro-inflammatory cytokines.
There is an increased synovial infiltration with C-kit positive mast cells in non-psoriatic and psoriatic SpA. Inhibition of C-kit in vitro leads to a reduction of proinflammatory cytokine production by synovial biopsies. These data suggest a role for mast cells in driving and/or sustaining the synovial inflammation in SpA.
To cite this abstract, please use the following information:
Noordenbos, Troy, Yeremenko, Nataliya, Cantaert, Tineke, Teitsma, Christine, van de Sande, Marleen, Tak, Paul P., et al; Mast Cells Contribute to Synovial Inflammation in Non-Psoriatic and Psoriatic Spondyloarthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1449