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: 4.12). 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.

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    ABSTRACT: Background Alterations of B cell subset distribution have been described in the peripheral blood (PB) of rheumatoid arthritis (RA) patients, but no data are available on differences between the onset and the established phases of the disease. The purpose of the study was to clarify whether a peculiar distribution of B cell subsets characterizes RA onset, thus leading to a more favorable clinical response to treatment, and to evaluate the possible association of a particular B cell subpopulation with response to therapy.Results122 RA patients were enrolled: 25 had symptom duration less than 3 months and were defined as having ¿very early RA¿ (VERA), and 43 had symptom duration from more than 3 months up to one year (early-RA: ERA). The other 54 RA patients had long-standing RA (LSRA). At baseline and at 6-month follow-up visit peripheral blood samples were collected and analyzed by flow cytometry for the distribution of circulating B cell subsets by staining with surface markers CD45, CD19, CD38, CD27 and IgD and intracellular marker ZAP70.VERA and ERA patients showed higher percentages and absolute counts of circulating antigen inexperienced naïve B cells (IgD¿+¿CD27-) and lower percentages and absolute numbers of double negative (IgD-CD27-) memory B cells and plasmablasts (CD38¿+¿CD27+) compared to LSRA patients. At the multivariate analysis, a higher frequency of naïve B cells (IgD¿+¿CD27-) at baseline arose as significant predictor of CDAI remission, together with ¿having VERA disease¿ and a low disease activity at baseline.Conclusions The onset of RA is characterized by higher percentages and absolute numbers of naïve B cells and lower numbers of plasmablasts and double negative memory B cells compared to established RA. Naïve B cells could represent a promising biomarker of outcome.
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    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;

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