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Anti-citrullinated protein antibodies contribute to platelet activation in rheumatoid arthritis.
Habets, Kim L L; Trouw, Leendert A; Levarht, E W Nivine; Korporaal, Suzanne J A; Habets, Petra A M; de Groot, Philip; Huizinga, Tom W J; Toes, René E M.
Afiliación
  • Habets KL; Department of Rheumatology, Leiden University Medical Centre, C1-R, PO Box 9600, 2300, RC, Leiden, the Netherlands. k.l.l.habets@lumc.nl.
  • Trouw LA; Department of Rheumatology, Leiden University Medical Centre, C1-R, PO Box 9600, 2300, RC, Leiden, the Netherlands. l.a.trouw@lumc.nl.
  • Levarht EW; Department of Rheumatology, Leiden University Medical Centre, C1-R, PO Box 9600, 2300, RC, Leiden, the Netherlands. e.w.n.levarht@lumc.nl.
  • Korporaal SJ; Department of Clinical Chemistry and Haematology, University Medical Centre, Utrecht, the Netherlands. j.a.korporaal@umcutrecht.nl.
  • Habets PA; Division of Biopharmaceutics, Leiden Amsterdam Centre for Drug Research, University of Leiden, Leiden, the Netherlands. j.a.korporaal@umcutrecht.nl.
  • de Groot P; Knowledge Centre Forensic Psychiatric Care, Rekem Psychiatric Hospital, Rekem, Belgium. petra.habets@opzcrekem.be.
  • Huizinga TW; Department of Clinical Chemistry and Haematology, University Medical Centre, Utrecht, the Netherlands. ph.g.degroot@umcutrecht.nl.
  • Toes RE; Department of Rheumatology, Leiden University Medical Centre, C1-R, PO Box 9600, 2300, RC, Leiden, the Netherlands. t.w.j.huizinga@lumc.nl.
Arthritis Res Ther ; 17: 209, 2015 Aug 24.
Article en En | MEDLINE | ID: mdl-26268317
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos Cíclicos / Artritis Reumatoide / Autoanticuerpos / Activación Plaquetaria / Citrulina Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Arthritis Res Ther Asunto de la revista: REUMATOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos Cíclicos / Artritis Reumatoide / Autoanticuerpos / Activación Plaquetaria / Citrulina Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Arthritis Res Ther Asunto de la revista: REUMATOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido