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Increased levels of peptidylarginine deiminase 2 in synovial fluid from
anti-CCP-positive rheumatoid arthritis patients: Association with disease
activity and inflammatory markers
#MMPMID26880831
Damgaard D
; Senolt L
; Nielsen CH
Rheumatology (Oxford)
2016[May]; 55
(5
): 918-27
PMID26880831
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OBJECTIVE: To quantify peptidylarginine deiminase 2 (PAD2) in SF of RA patients
and OA patients, and to determine the association between PAD2 levels, disease
activity and inflammatory markers in RA. METHODS: Blood and SF samples were
obtained from 39 RA patients and 40 patients with OA. PAD2 content and PAD
activity were measured by means of in-house assays. TNF-?, IL-1?, IL-6, IL-8,
IL-10 and IL-12 were measured using flow cytometry. RESULTS: PAD2 levels and PAD
activity were higher in SF from RA than OA patients (P < 0.0001 and P = 0.03,
respectively), as were all cytokine levels (P < 0.0001-0.05). SF PAD2 levels were
higher among anti-CCP-positive patients than among anti-CCP-negative patients (P
= 0.005). PAD2 levels in SF from RA patients correlated with disease activity, as
assessed by DAS28 (P < 0.005). Moreover, SF PAD2 levels correlated with
circulating CRP and anti-CCP levels (P < 0.0006), as well as with leucocyte
count, IL-6, IL-8 and IL-10 levels in SF (P < 0.0001-0.02). PAD activity in SF
was higher in RA patients than in OA patients, and correlated with PAD2
concentration. CONCLUSION: Extracellular PAD2 levels in SF correlate with disease
activity in RA patients. Anti-CCP-positive RA patients have higher PAD2 levels in
SF than anti-CCP-negative RA patients and OA patients. Since we could demonstrate
enzymatically active PADs in SF, we propose that free, extracellular PAD is of
pathogenic relevance.
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