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

Abstract

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.

• Authors: Kim L L Habets, Leendert A Trouw, E W Nivine Levarht, Suzanne J A Korporaal, Petra A M Habets, Philip de Groot, Tom W J Huizinga, René E M Toes
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 17 Pg. 209 (Aug 24 2015) ISSN: 1478-6362 [Electronic] England
• PMID: 26268317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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