Background/Purpose:

Patients with rheumatoid arthritis (RA) die prematurely of cardiovascular disease (CVD). Platelet mediated thrombosis is a major cause of CVD.  Platelets amplify inflammation in RA via the collagen receptor, glycoprotein (GP) VI. When platelets are activated, the GPVI receptor is shed and present in plasma as soluble GPVI (sGPIV). Since sGPVI  is a marker of  global platelet activation, we investigated whether sGPVI differs in patients with active RA in comparison with  patients with  low RA disease activity. Moreover, since cytokines associated with disease activity in RA may effect platelet activation, we also assessed the relationship between sGPVI and plasma cytokine levels in this cohort.

Methods:

We prospectively assayed blood samples from healthy donors (n=5), patients with active RA (n=13), and controlled RA (n=10), respectively. Disease activity assessment comprised of serological markers (ESR,CRP, fibrinogen), patient measures (VASDA), evaluator global assessment, and the DAS-28 score. Platelet activation was assessed by measuring sGPVI. Plasma was 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 ELISA.  Serum levels of tumor necrosis factor (TNF)α, interleukin (IL)1β, IL6, IL8, IL10, IL12p70 and interferon (IFN)δ were measured by multiplex ELISA and a Spearman’s rank-order correlation was used to test significance.

Results:

Mean plasma sGPVI was significantly higher in patients with active RA (14 ±7ng/ml;(mean±SEM) p<0.005) compared to both stable RA (5±1ng/ml) and controls (5±2ng/ml) demonstrating that platelet activation occurs in active RA. Mean plasma IL-10 was significantly higher in stable RA patients (39±31 pg/ml; p <0.005) compared to both active RA and controls (15±8 and 2.24±0.33pg/ml respectively). There was no association with any measured cytokine and sGPVI levels apart from IL-10, which was negatively correlated with sGPVI in these 28, matched plasma samples (-0.432; p ≤0.045).

Conclusion:

Platelet hyper–reactivity in patients with active RA likely contributes to the associated adverse cardiovascular outcomes. sGPVI is a marker for platelet activation  in active RA.  The anti-inflammatory cytokine  IL10, known to play a modulatory role in endothelial cell damage and platelet adhesion, may negatively regulate platelet activation in active RA. These effects of IL-10 could potentially be exploited in the management of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interleukin-10-negatively-correlates-with-glycoprotein-vi-related-platelet-activation-in-rheumatoid-arthritis-ra-a-novel-potential-target-of-cardiovascular-morbidity-in-ra/