Background Physiologically, platelets can distribute systemically by circulation and contribute to hemostasis after activation . Activated platelets acquire functional abilities of adhesion, and morphological changes, and releasing ingredients or small vesicles called microparticles (MP) . On the other hand, recent reports have been shown that platelets include a lot of humoral factors such as chemokines, cytokines and growth factors , suggesting that platelets and MPs can be vectors for transferring these factors to the lesions and contribute to disease processes such as inflammation .
Objectives To examine the hypothesis that platelets is involved in the pathogenesis of Rheumatoid arthritis (RA), we investigated the activation status of circulating platelets and the association with clinical characteristics using a brief evaluation system.
Methods Fifty-seven patients with RA were involved and 7 primary Sjogren's syndrome (pSS), 4 systemic lupus erythematosus (SLE), and 16 healthy controls were examined as controls. Fractions of platelets and microparticles were determined by the size less than 1mm in diameter using forward and side scatter of flow cytometry with Megamix® beads. Activated platelets were detected by CD41+CD62P+ population in the platelet fraction. Platelet-derived MPs were determined CD41+annexinV+ population in microparticle fraction. Activation status of platelets was examined by the ratio of CD62P-positive to negative platelet population. Proportion of platelet-derived MPs was examined by the ratio of platelet-derived MPs to platelets population. Correlation of activation status of platelets, MP and clinical parameters of patients with RA were also examined.
Results Proportion of activated platelets and that of MPs were higher in RA compared to HC (P<0.001, P<0.00001, respectively). Serial analysis of 6 patients, who were treated with methotrexate and/or biologics and achieved improvement of disease activity at 12 week after the treatment, revealed significant decrease of these proportions (P<0.03). On the other hand, these parameters were comparable between HC and pSS or SLE. In patients with RA, proportion of activated platelets and those of MPs were correlated each other (P<0.0001). Interestingly, proportion of activated platelets and MPs were positively correlated with clinical parameters of patients with RA such as serum CRP (P<0.05, P<0.05, respectively), erythrocyte sedimentation rate (P<0.03, P<0.05, respectively), and CDAI (P<0.05, P<0.05, respectively), which were markers of disease activity. Whereas, no correlation was observed with age, sex, tender- and swollen-joint count, HAQ, nor MMP-3.
Conclusions In patients with RA, platelets are activated and their activation status is correlated with the inflammatory markers and disease activity, suggesting that activation of platelets can contribute to the process of systemic chronic inflammation in the pathogenesis of RA.
Bizzozero G et al. Sur un nouvel element morphologue du sang chez les mammiferes et son importance dans la thombose et dans la coagulation. Arch Ital Biol 1:1–5, 1882.
George JN. Platelets. Lancet 355:1531–9, 2000.
Morrell CN et al. Emerging roles for platelets as immune and inflammatory cells. Blood 123:2759–2767, 2014
Semple JW et al. Platelets and the immune continuum. Nat Rev Immunol 11:264–274, 2011.
Disclosure of Interest None declared