Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Glucocorticoids Decrease the Expression of Synovial Citrullinated Proteins in Rheumatoid Arthritis
Makrygiannakis, Dimitrios, Revu, Shankar, Neregard, Petra, Engstrom, Marianne, Klareskog, Lars, Catrina, Anca Irinel
Citrullination has previously been reported to be an inflammation associated process. Peptidylarginine deiminase (PAD) 2 and 4 are the PAD enzymes expressed in the rheumatoid arthritis (RA) synovium, while a mouse monoclonal antibody (F95) has been found to be associated with an intracellular pattern which is specific for RA synovium and which correlates with anti-citrullinated-protein antibody levels. The aim of the current study was to compare the expression of PAD2, PAD4 and citrullinated proteins between RA and healthy synovium and to study the effect of anti rheumatic drugs on synovial expression of CP and PAD enzymes. (MTX), infliximab (IFX) and etanercept (ETA) on PAD2, PAD4 and F95 expression in RA synovium.
Synovial biopsies were obtained from 15 RA patients treated with intra-articular glucocorticoids (IAG), 13 RA patients treated with methotrexate (MTX), 9 RA patients treated with infliximab (IFX) and 13 RA patients treated with etanercept (ETA). Synovial tissue was also obtained from 8 healthy individuals. The presence of PAD2 and PAD4 was immunohistochemically detected with 2 rabbit polyclonal antibodies for each enzyme and the presence of citrullinated proteins with the F95 antibody. Biopsies were evaluated by double blind semi-quantitative analysis on a 4-grade scale (03). Additionally synovial tissue from an RA patient obtained during open joint surgery was cultured in vitro to further study the direct effect of the drugs on synovial citrullination. Statistical analysis was performed using the Wilcoxon test.
F95 staining was present in 40/50 RA patients (both extracellular and intracellular) while none of the 8 healthy individuals exhibited an intracellular pattern and only one exhibited an extracellular pattern in low amounts. PAD2 expression was higher in RA in comparison to healthy synovial tissue, while PAD4 expression did not differ.
Treatment with MTX and TNF antagonists did not alter the expression of PAD enzymes and CP, with the exception of a reduction in PAD4 expression (statistical significance with one of the 2 antibodies used) in the IFX treated group. In contrast, IAG treatment resulted in down-regulation of both the expression of intracellular citrullinated proteins (F95) and of the PAD4 enzyme. This finding was confirmed in the cultured biopsy demonstrating no changes in the expression of PAD2 and a decrease of F95 and PAD4 expression following glucocorticoid treatment.
The RA specific pattern of intracellular citrullination is absent in healthy synovium and specific targeted by glucocorticoids.
To cite this abstract, please use the following information:
Makrygiannakis, Dimitrios, Revu, Shankar, Neregard, Petra, Engstrom, Marianne, Klareskog, Lars, Catrina, Anca Irinel; Glucocorticoids Decrease the Expression of Synovial Citrullinated Proteins in Rheumatoid Arthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :436