Increased levels of peptidylarginine deiminase 2 in synovial fluid from anti-CCP-positive rheumatoid arthritis patients: Association with disease activity and inflammatory markers

TY - JOUR

T1 - Increased levels of peptidylarginine deiminase 2 in synovial fluid from anti-CCP-positive rheumatoid arthritis patients

T2 - Association with disease activity and inflammatory markers

AU - Damgaard, Dres

AU - Senolt, Ladislav

AU - Nielsen, Claus H

N1 - © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected].

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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-α, IL-1-β, 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-CCPpositive 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.

AB - 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-α, IL-1-β, 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-CCPpositive 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.

U2 - 10.1093/rheumatology/kev440

DO - 10.1093/rheumatology/kev440

M3 - Journal article

C2 - 26880831

SN - 1462-0324

VL - 55

SP - 918

EP - 927

JO - Rheumatology

JF - Rheumatology

IS - 5

ER -