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

Rhumatologie, Hôpitaux Universitaires de Strasbourg, Centre de Référence National des Maladies Auto-Immunes Systémique Rares, EA 3432 Physiopathologie des Arthrites, Strasbourg, France.
Arthritis research & therapy (Impact Factor: 4.27). 08/2009; 11(4):R114. DOI: 10.1186/ar2773
Source: PubMed

ABSTRACT 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.
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.
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.
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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sjögren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that the κ (P < 0.0001) and λ (P = 0.0003) free light chains and the κ : λ ratio (P = 0.0049) are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase of κ and λ free light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension.
    International Journal of Rheumatology 01/2013; 2013:426759.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To examine blood B cell subsets in patients with rheumatoid arthritis (RA) prior to B cell depletion therapy and to assess their potential as predictors of clinical response to rituximab (RTX). Blood B cell subsets were assessed by flow cytometry in 208 RA patients included in an RTX retreatment study (assessed prior to RTX treatment) and in 47 age-matched controls. Expression of BAFF receptor (BAFF-R) on B cells and serum B cell biomarkers was also measured. B cell subsets and BAFF-R expression were compared between RA patient and control populations. Univariate and multivariate analyses were performed to identify baseline factors associated with a European League Against Rheumatism response 24 weeks after 1 cycle of RTX. Mean ± SD counts of both CD27- naive and CD27+ memory B cells were decreased in RA patients (188.6 ± 121.4/mm(3)) compared with controls (257.3 ± 154.1/mm(3)) (P = 0.001) and were partially restored in patients treated with methotrexate (MTX) plus anti-tumor necrosis factor compared with patients treated with MTX alone. Within the CD27+ memory B cells, the CD27+IgD- switched memory subtype was selectively decreased, irrespective of treatment. The frequency of CD27+ memory B cells correlated inversely with levels of several B cell activation biomarkers in RA. Serum BAFF level and BAFF-R expression was comparable in RA patients and controls. A low baseline CD27+ memory B cell frequency was associated with a greater clinical response to RTX (odds ratio 0.97 [95% confidence interval 0.95-0.99], P = 0.0015). In B cell depletion therapy-naive RA patients, a low frequency of CD27+ memory B cells correlated with levels of serum B cell activation biomarkers and may predict response to RTX. These results suggest that low memory B cell frequency may be indicative of a B cell-driven RA subtype that is more sensitive to B cell depletion therapy.
    Arthritis & Rheumatology 12/2011; 63(12):3692-701. · 7.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To assess the serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) level in rheumatoid arthritis (RA) patients in view of different treatment regimens received and evaluate its relation with disease activity. Patients and methods Ninety female RA patients were included. Sixty were on disease modifying anti-rheumatic drugs (DMARDs); 34 on hydroxychloroquine (HCQ) plus methotrexate (MTX), 26 on leflunomide (LFN) plus MTX and 30 newly diagnosed cases not yet on any treatment. Thirty age and gender matched healthy subjects served as controls. Full history taking, clinical examination and relevant laboratory investigations were performed. Disease activity score, in 28 joints (DAS-28), was calculated. Results Serum BAFF level was significantly higher in patients (1.82 ± 0.91 ng/ml) compared to control (0.71 ± 0.33 ng/ml; p < 0.001). There was a significantly lower BAFF and disease activity in patients receiving DMARDs (1.55 ± 0.73 ng/ml and 3.08 ± 0.73) compared to new cases (2.36 ± 1.02 ng/ml and 3.46 ± 0.82) (p < 0.001 and p = 0.036, respectively). Those receiving HCQ + MTX had a lower BAFF level (1.29 ± 0.51 ng/ml) compared to those receiving LFN + MTX (1.94 ± 0.85 ng/ml; p = 0.002). The BAFF level significantly correlated with the presence of anti-CCP antibodies, DAS28 and MTX dose in all RA patients (r = 0.24, p = 0.02; r = 0.504, p < 0.001; r = 0.51, p < 0.001, respectively). Only DAS28 and MTX dose would highly influence the BAFF level (p = 0.015 and p = 0.001, respectively). Conclusion Elevated level of BAFF in RA has been confirmed with a notable relation to disease activity making it a promising marker. The beneficial effect of hydroxychloroquine in dampening BAFF level throws light on the importance of considering it in combination among the newly developed biologics that also target B-cells.
    Bulletin of Faculty of Pharmacy, Cairo University. 06/2014;

Full-text (3 Sources)

Available from
May 21, 2014