Research article

Local administration of glucocorticoids decrease synovial citrullination in rheumatoid arthritis

Dimtrios Makrygiannakis, Shankar Revu, Marianne Engstrom, Erik af Klint, Anthony P Nicholas, Ger JM Pruijn and Anca I Catrina

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Arthritis Research & Therapy 2012, 14:R20 doi:10.1186/ar3702

Published: 27 January 2012

Abstract (provisional)

Introduction

Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation in the presence of specific autoimmunity. As a result, the present study examines the possibility that effective anti rheumatic treatment will decrease the level of synovial citrullination.

Methods

Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patients before and 2 weeks after an intra-articular glucocorticoid injection, 8 healthy individuals and 5 patients with osteoarthritis. Synovial inflammation was assessed by double blind semi quantitative analysis of lining thickness, cell infiltration and vascularity using a 4 points scale. Expression of citrullinated proteins (CP) with the monoclonal antibody F95 and peptidylarginine deiminase (PAD) 2 and 4 was assessed immunohistochemically by double blind semi-quantitative analysis. In vitro synovial fluid (SF), peripheral blood (PB) mononuclear cells (MC) and synovial explants obtained from RA patients were incubated with dexamethasone and analyzed by immunhistochemistry for expression of CP as well as PAD2 and PAD4 enzymes.

Results

Presence of synovial CP was almost exclusive in RA compared to healthy synovium and correlated with the degree of local inflammation. Treatment with glucocorticoids but not methotrexate alters expression of synovial CP and PAD enzymes, in parallel with a decrease of synovial inflammation. Ex vivo and in vitro studies suggest also a direct effect of glucocorticoids on citrullination as demonstrated by the decrease in the level of citrullination and PAD expression following incubation of SFMC and synovial explants with dexamethasone.

Conclusion

Synovial citrullination and PAD expression is depended on local inflammation and targeted by glucocorticoids.