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Increased levels of circulating microparticles in primary Sjögren's syndrome

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Cell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Jérémie Sellam1, Valérie Proulle2, Astrid Jüngel3, Marc Ittah1, Corinne Miceli Richard1, Jacques-Eric Gottenberg1, Florence Toti4, Joelle Benessiano5, Steffen Gay3, Jean-Marie Freyssinet4 and Xavier Mariette1

1 Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), INSERM U802, Université Paris-Sud 11, 78 rue du Général Leclerc, 94270, Le Kremlin Bicêtre, France

2 Hématologie, Hôpital Bicêtre, APHP, INSERM U770, Université Paris-Sud 11, 78 rue du Général Leclerc, 94270, Le Kremlin Bicêtre, France

3 Center of Experimental Rheumatology, University Hospital Zurich, Gloriastrasse 25, CH 8091 Zurich, Switzerland

4 INSERM Unité 770 et Université de Strasbourg, 78 rue du Général Leclerc, 94270, Le Kremlin Bicêtre, France

5 Centre de Ressources biologiques – Centre d’Investigation clinique, Hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France

Arthritis Research & Therapy 2009, 11:R156doi:10.1186/ar2833

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/11/5/R156

Received: 6 August 2009
Revisions requested: 27 August 2009
Revisions received: 22 September 2009
Accepted: 15 October 2009
Published: 15 October 2009

© 2009 Sellam et al.; licensee BioMed Central Ltd.

Abstract

Introduction

Cell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods

We measured plasma levels of total, platelet and leukocyte MPs by prothrombinase capture assay and flow cytometry in 43 patients with pSS, 20 with SLE and 24 with RA and in 44 healthy controls (HCs). Secretory phospholipase A2 (sPLA2) activity was assessed by fluorometry. Soluble CD40 ligand (sCD40L) and soluble P-selectin (sCD62P), reflecting platelet activation, were measured by ELISA.

Results

Patients with pSS showed increased plasma level of total MPs (mean ± SEM 8.49 ± 1.14 nM PS equivalent (Eq), P < 0.0001), as did patients with RA (7.23 ± 1.05 n PS Eq, P = 0.004) and SLE (7.3 ± 1.25 nM PS Eq, P = 0.0004), as compared with HCs (4.13 ± 0.2 nM PS Eq). Patients with AIDs all showed increased level of platelet MPs (P < 0.0001), but only those with pSS showed increased level of leukocyte MPs (P < 0.0001). Results by capture assay and flow cytometry were correlated. In patients with high disease activity according to extra-glandular complications (pSS), DAS28 (RA) or SLEDAI (SLE) compared with low-activity patients, the MP level was only slightly increased in comparison with those having a low disease activity. Platelet MP level was inversely correlated with anti-DNA antibody level in SLE (r = -0.65; P = 0.003) and serum β2 microglobulin level in pSS (r = -0.37; P < 0.03). The levels of total and platelet MPs were inversely correlated with sPLA2 activity (r = -0.37, P = 0.0007; r = -0.36, P = 0.002, respectively). sCD40L and sCD62P concentrations were significantly higher in pSS than in HC (P ≤ 0.006).

Conclusions

Plasma MP level is elevated in pSS, as well as in SLE and RA, and could be used as a biomarker reflecting systemic cell activation. Level of leukocyte-derived MPs is increased in pSS only. The MP level is low in case of more severe AID, probably because of high secretory phospholipase A2 (sPLA2) activity, which leads to consumption of MPs. Increase of platelet-derived MPs, sCD40L and sCD62P, highlights platelet activation in pSS.

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