Article

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.

0 Bookmarks
 · 
90 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abatacept (ABA) is a chimeric molecule, able to block the CD28-mediated costimulatory pathway. To evaluate the hypothesis that, through this mechanism of action, ABA may down-modulate the immune responses of B lymphocytes in rheumatoid arthritis (RA), we investigated the serum levels of immunoglobulins (Ig), free light chains (FLC), anticitrullinated protein antibodies (ACPA), and rheumatoid factor (RF), as well as the number of B lymphocytes differentiated into post-switch memory cells in patients treated with ABA. The serum levels of Ig, FLC, different ACPA, RF isotypes, and the B cell phenotype were longitudinally evaluated in 30 patients with RA treated with ABA. At baseline, the proportion of total and post-switch memory B cells was lower in RA than in healthy individuals. After 6 months of ABA treatment we observed significant reductions of serum levels of IgG, IgA, and IgM, as well as FLC, with a normalization in many patients who had initially abnormal values. A significant reduction of the titers of IgG- and IgA-ACPA, as well as of IgM-, IgA-, and IgG-RF was also observed. A decrease of autoantibodies below the upper limits of normal values was found in 2 of 26 patients (8%) initially seropositive for IgG-ACPA, 1 of 14 (7%) for IgA-ACPA, 5 of 22 (23%) for IgM-RF, 7 of 22 (30%) for IgA-RF, and 5 of 16 (31%) for IgG-RF. After treatment, the proportion of circulating post-switch memory B cells was also further significantly decreased. ABA treatment in patients with RA can reduce signs of polyclonal B cell activation, inducing a trend toward normalization of serum levels of different classes of Ig and of FLC, decreasing titers of ACPA and RF, and percentages of post-switch memory B cells.
    The Journal of Rheumatology 03/2014; 41(4). DOI:10.3899/jrheum.130905 · 3.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    BMC Immunology 09/2014; 15(1):28. DOI:10.1186/s12865-014-0028-1 · 2.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Immunoglobulin free light chains (FLC) represent biomarkers of B cell activity in rheumatoid arthritis (RA) and are associated with all-cause mortality in the general population. Our objective was to evaluate the relationships of serum FLC to preclinical disease, RA characteristics, and mortality in RA compared to non-RA subjects. A population-based study in Olmsted County, Minnesota, USA, was performed by crosslinking a large cohort in the general population having available serum FLC measurements with established RA incidence and prevalence cohorts. Serum κ, λ, and total FLC and their trends relative to RA incidence were compared between RA and non-RA subjects. Regression models were used to determine the associations between FLC, disease characteristics, and mortality, testing for differential effects of FLC on mortality in RA. Among 16,609 subjects, 270 fulfilled the criteria for RA at the time of FLC measurement. Mean total FLC were significantly higher in RA compared to non-RA subjects (4.2 vs 3.3 mg/dl, p < 0.001). FLC became elevated 3-5 years before the clinical onset of RA and remained elevated during followup. Polyclonal FLC were found to predict higher mortality in persons with RA, though elevation to the highest decile had a relatively lower effect on mortality in RA compared to non-RA subjects. Elevation of serum FLC precedes the development of RA and may be useful in monitoring B cell activity and disease progression. FLC are associated with mortality among patients with RA as well as the general population.
    The Journal of Rheumatology 01/2015; 42(2). DOI:10.3899/jrheum.140543 · 3.17 Impact Factor

Full-text (4 Sources)

Download
21 Downloads
Available from
May 21, 2014