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Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis.

Abstract：

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 examined the possibility that effective antirheumatic 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 intraarticular glucocorticoid injection, and eight healthy volunteers. Synovial inflammation was assessed with double-blind semiquantitative analysis of lining thickness, cell infiltration, and vascularity by using a 4-point scale. Expression of citrullinated proteins (CPs) with the monoclonal antibody F95 and peptidylarginine deiminase (PAD) 2 and 4 was assessed immunohistochemically with double-blind semiquantitative analysis. In vitro synovial fluid (SF), peripheral blood (PB), mononuclear cells (MCs), and synovial explants obtained from RA patients were incubated with dexamethasone and analyzed with immunohistochemistry for expression of CP as well as PAD2 and PAD4 enzymes. RESULTS:The presence of synovial CP was almost exclusive in RA compared with 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 after incubation of SFMC and synovial explants with dexamethasone. CONCLUSION:Synovial citrullination and PAD expression are dependent on local inflammation and targeted by glucocorticoids.

journal_name

Arthritis Res Ther

journal_title

Arthritis research & therapy

authors

Makrygiannakis D,Revu S,Engström M,af Klint E,Nicholas AP,Pruijn GJ,Catrina AI

doi

10.1186/ar3702

subject

Has Abstract

pub_date

2012-01-27 00:00:00

pages

R20

issue

1

eissn

1478-6354

issn

1478-6362

pii

ar3702

journal_volume

14

pub_type

临床试验,杂志文章

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