Open Access Research article

Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort

Jacques-Eric Gottenberg1, Corinne Miceli-Richard1, Béatrice Ducot2, Philippe Goupille3, Bernard Combe4 and Xavier Mariette5*

Author Affiliations

1 Rhumatologie, Hôpitaux Universitaires de Strasbourg, Centre de Référence National des Maladies Auto-Immunes Systémique Rares, EA 3432 « Physiopathologie des Arthrites », Strasbourg, France

2 Institut Pour la Santé et la Recherche Médicale (INSERM) Unité 822, 'Epidémiologie, Démographie et Sciences Sociales', IFR69; Institut National d'Etudes Démographiques (INED); Université Paris 11, Le Kremlin-Bicêtre, France

3 CHRU de Tours; UMR CNRS 6239, Université de Tours; INSERM CIC-202, Tours, France

4 Immuno-Rhumatologie, Hôpital Lapeyronie, Université Montpellier 1, UGM 5535, Montpellier, France

5 Rhumatologie, INSERM U802, Université Paris-Sud 11, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France

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Arthritis Research & Therapy 2009, 11:R114 doi:10.1186/ar2773

Published: 23 July 2009

Abstract

Introduction

Little is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort.

Methods

In the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks but less than 6 months), 710 patients were assessed at 1 year and either met the 1987 American College of Rheumatology criteria for RA (n = 578) or had undifferentiated arthritis (n = 132). Baseline serum samples of patients naïve to corticosteroid and disease-modifying antirheumatic drug treatment were assessed for beta2-microglobulin, IgG, IgA, IgM, immunoglobulin free light chains of immunoglobulins, and B-cell activating factor of the tumor necrosis factor family (BAFF). The BAFF gene 871T>C polymorphism was genotyped in all patients.

Results

All markers of B-cell activation except BAFF and IgM were significantly higher in patients with early RA than those with undifferentiated arthritis. Anti-cyclic citrullinated peptide (anti-CCP) and beta2-microglobulin were associated with a diagnosis of early RA in the multivariate analysis. Markers of B-cell activation, except BAFF, were associated with disease activity, rheumatoid factor and anti-CCP secretion. The BAFF gene polymorphism was not associated with early RA.

Conclusions

Markers of B-cell activation are elevated in patients with early RA, compared with undifferentiated arthritis, independently of any systemic increase in BAFF secretion, and correlate with disease activity. This study sheds new light on the early pathogenic role of B-lymphocytes in RA and suggests that targeting them might be a useful therapeutic strategy in early RA.