Soluble glycoprotein VI, a specific marker of platelet activation is increased in the plasma of subjects with seropositive rheumatoid arthritis

John R. Stack*, Anne Madigan, Laura Helbert, Eimear Dunne, Elizabeth E. Gardiner, Robert K. Andrews, Roisin Finan, Elizabeth Smyth, Dermot Kenny, Geraldine M. McCarthy

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    Objectives: Anti-citrullinated protein antibodies (ACPA) have been shown to cause platelet activation in vitro, through the low-affinity immunoglobulin G (IgG) receptor (FcγRIIa) on platelets. Platelet activation via engagement of FcγRIIa results in proteolytic cleavage and shedding of platelet specific glycoprotein VI (GPVI) which can be detected in the plasma as soluble GPVI (sGPVI). We hypothesized that plasma levels of sGPVI would be increased among patients with seropositive RA as a consequence of antibody-induced platelet activation and GPVI shedding. Methods: Samples from 84 patients with RA (65 seropositive and 19 seronegative) and 67 healthy controls were collected prospectively and analysed for sGPVI using a standardised ELISA. Results: Patients with seropositive RA had significantly higher levels of sGPVI compared to seronegative RA and controls. Median (IQR) sGPVI levels were 4.2 ng/ml (3.2, 8.0) in seropositve RA, 2.2 ng/ml (1.5, 3.5) in seronegative RA and 2.2 ng/ml (1.6, 3.4) in controls (p<0.0001). sGPVI levels correlated with ACPA titres (r = 0.32, p = 0.0026) and with RF titres (r = 0.48, p<0.0001). Conclusion: Plasma sGPVI, a specific marker of platelet activation is increased among patients with seropositive RA.

    Original languageEnglish
    Article numbere0188027
    JournalPLoS ONE
    Volume12
    Issue number11
    DOIs
    Publication statusPublished - Nov 2017

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