Session Type: Abstract Submissions (ACR)
Patients with inflammatory arthritis (IA) such as rheumatoid arthritis (RA) are at high risk of cardiovascular mortality. Increased platelet reactivity is a risk marker for adverse cardiovascular events. We and others have demonstrated that there is increased platelet reactivity in blood from patients with IA. Recent data has shown that platelets amplify inflammation in the joint in IA via the collagen receptor, glycoprotein(GP)VI followed by the production of proinflammatory platelet microparticles1. When platelets are activated, the GPVI receptor is shed and detectable in plasma as soluble GPVI (sGPVI) Our hypothesis was that both plasma and synovial fluid (SF) sGPVI would be raised in patients with IA compared to those with osteoarthritis (OA).
Methods: Following ethics approval and informed consent healthy normal donors (n=20) were compared to 43 consecutively recruited patients (OA, n=15, IA, n=28). SF samples were obtained from knee joints when indicated for clinical evaluation and/or joint injection. Plasma and SF samples were centrifuged at 720g and then 20000g to ensure that no platelets or platelet derived microparticles were present in the sample and sGPVI levels were measured by ELISA2.
Results: Mean plasma sGPVI was similar in normal controls and patients with OA (30±6 ng/ml vs 31±6 ng/ml respectively). In contrast, mean plasma sGPVI was 51±14 ng/ml in patients with IA compared to both normal and OA individuals (P<0.005). SF sGPVI was assayed in 14 patients (IA, n=8, OA, n=6). Seven patients (IA n=4, OA, n=3) had plasma and synovial fluid samples taken simultaneously. SF sGPVI was significantly elevated in patients with IA compared to those with OA. Moreover plasma levels of sGPVI closely correlated with SF levels in these matched samples (rs = 0.995).
Our data shows that sGPVI is easily measured in both plasma and SF. It also suggests the potential value of sGPVI as a marker of both disease activity and platelet reactivity in arthritis. Finally, it further supports an active role of platelets in promoting inflammation locally within the joint.
1. Boilard E, Nigrovic PA, Larabee K, Watts GF, Coblyn JS, Weinblatt ME, Massarotti EM, Remold-O’Donnell E, Farndale RW, Ware J, Lee DM Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science. 2010 Jan 29;327(5965):580-3
2. Al-Tamimi M, Mu FT, Moroi M, Gardiner EE, Berndt MC, Andrews RK. Measuring soluble platelet glycoprotein vi in human plasma by elisa. Platelets. 2009;20:143-149
A. M. Madigan,
P. A. MacMullan,
G. M. McCarthy,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/soluble-glycoprotein-vi-a-novel-risk-marker-for-thrombosis-in-patients-with-inflammatory-arthritis/