Anti-citrullinated protein antibodies contribute to platelet activation in rheumatoid arthritis

Arthritis Res Ther. 2015 Aug 24;17(1):209. doi: 10.1186/s13075-015-0665-7.


Introduction: Although the role of platelets in rheumatoid arthritis (RA) is relatively unexplored, recent studies point towards a contribution of platelets in arthritis. We set out to determine platelet phenotype in RA and studied whether this could be influenced by the presence of anti-citrullinated protein antibodies (ACPA).

Methods: Platelets from healthy controls were incubated in the presence of plasma of patients with RA or age- and sex-matched healthy controls and plasma from ACPA(neg) or ACPA(pos) patients or in the presence of plate-bound ACPA. Characteristics of platelets isolated from patients with RA were correlated to disease activity.

Results: Platelets isolated from healthy controls displayed markers of platelet activation in the presence of plasma derived from RA patients, as determined by P-selectin expression, formation of aggregates and secretion of soluble CD40 ligand (sCD40L). Furthermore, levels of P-selectin expression and sCD40L release correlated with high ACPA titres. In accordance with these findings, enhanced platelet activation was observed after incubation with ACPA(pos) plasma versus ACPA(neg) plasma. Pre-incubation of platelets with blocking antibodies directed against low-affinity immunoglobulin G receptor (FcγRIIa) completely inhibited the ACPA-mediated activation. In addition, expression of P-selectin measured as number of platelets correlated with Disease Activity Score in 44 joints, C-reactive protein level, ACPA status and ACPA level.

Conclusions: We show for the first time that ACPA can mediate an FcγRIIa-dependent activation of platelets. As ACPA can be detected several years before RA disease onset and activated platelets contribute to vascular permeability, these data implicate a possible role for ACPA-mediated activation of platelets in arthritis onset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Blood Platelets / immunology
  • Blood Platelets / metabolism
  • CD40 Ligand / blood
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism
  • Citrulline / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • P-Selectin / blood
  • P-Selectin / immunology
  • P-Selectin / metabolism
  • Peptides, Cyclic / immunology*
  • Platelet Activation / immunology*


  • Autoantibodies
  • Immunoglobulin G
  • P-Selectin
  • Peptides, Cyclic
  • CD40 Ligand
  • Citrulline