Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Increased Activity of the platelet glycoprotein (GP) VI pathway in Patients with Rheumatoid Arthritis.
MacMullan1, Paul A., Dunne2, Eimear, Madigan1, Anne M., Berndt2, Michael C., Andrews3, Robert K., Gardiner3, Elizabeth E., Kenny2, Dermot
Recent experimental evidence using an animal model of rheumatoid arthritis (RA) has shown that platelet-derived microparticles exacerbate joint inflammation following engagement of the platelet-specific glycoprotein (GP) VI receptor by collagen (1). We have previously shown that GPVI engagement by collagen causes shedding of the soluble extracellular domain of GPVI (sGPVI) (2). Therefore we set out to evaluate 1) platelet aggregation in response to collagen and 2) plasma sGPVI levels in patients with RA.
Patients with an established diagnosis of RA were recuited consecutively. Those with a history of cardiovascular disease or who were receiving anti-platelet therapy or thromboembolic prophylaxis were excluded. Disease activity was assessed using standard inflammatory biomarkers and the internationally validated DAS-28 score. Platelet aggregation in response to increasing doses of collagen was tested in RA(n=62) patients and healthy controls (n=80). We also measured sGPVI levels by ELISA in double-spun plasma from a subset of these RA patients (n=10) and controls (n=20).
Patients with RA (n=62) had a significantly decreased platelet response to submaximal doses of collagen compared to healthy controls (n=80)(logEC50 1.99±0.09 vs 1.6±0.04, p<0.0001). Plasma sGPVI levels were several fold higher in RA patients (n=10) compared to controls (n=20) (mean±s.d; 49±14 vs 19±8 ng/mL, p<0.0001). There was no gross correlation between disease activity indices, platelet count, demographic data or cardiovascular risk factors and either platelet collagen aggregation response or sGPVI levels.
Patients with RA have decreased platelet response to GPVI stimulation by collagen compared to controls. Furthermore, levels of sGPVI are dramatically elevated in RA. This implies enhanced activity of the platelet GPVI pathway in RA, a phenomenon that could contribute to the underlying thrombotic risk in this patient population.
1.Boilard, E, Nigrovic, PA, Larabee, K, Watts, GF, Coblyn, JS & Weinblatt, ME, et al. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 2010;327(5965):5803.
To cite this abstract, please use the following information:
MacMullan, Paul A., Dunne, Eimear, Madigan, Anne M., Berndt, Michael C., Andrews, Robert K., Gardiner, Elizabeth E., et al; Increased Activity of the platelet glycoprotein (GP) VI pathway in Patients with Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2105