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: 3.75). 08/2009; 11(4):R114. DOI: 10.1186/ar2773
Source: PubMed


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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Available from: Xavier Mariette, Dec 23, 2013
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    • "The interpretation of their possible prognostic value thus requires caution and should take into account confounding factors. Yet, in the ESPOIR cohort, some B-cell markers, such as total IgA and kappa FLCs, turned out to be independently associated with radiographic erosions at disease onset [92], and IL-6 and IL-21 serum levels were also predictive of rapid radiographic progression at 1 year irrespective of clinical inflammation [93]. "
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    04/2014; 2014(6):1-14. DOI:10.1155/2014/681678
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    • "Analytes measured included soluble CD23 (sCD23-the low affinity FcεR), which is enzymatically cleaved and released from naïve B-cells following activation through Toll-Like Receptors (TLR) [19],  k and l  (SFLC) as measures of plasmablast activity. Overproduction of SFLC has been described in patients with RA [20] and suggested to be useful for monitoring disease activity [21] [22]. In an extension of our earlier reports [7] [23] we have also measured the levels of isotypes of the main autoantibody specificities found in RA, levels of protective antibodies, and of the key B-cell cytokine B-cell activating factor (BAFF-TNFSF13b or BLyS). "
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    Journal of Autoimmunity 12/2013; 50. DOI:10.1016/j.jaut.2013.12.002 · 8.41 Impact Factor
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    • "Serum samples were collected at enrolment and immediately stored at -80°C in a single biologic resource centre. A central laboratory was used for determining anti-citrullinated cyclic peptide (anti-CCP) antibodies (anti-CCP2; Dia-Sorin, Saluggia (Vercelli), Italy; positive >50 U/ml) and rheumatoid factor (RF) (Menarini France, Rungis Cedex, France; positive >9 IU/ml) with enzyme-linked immunosorbent assay (ELISA), as previously described [23]. ELISA kits were used for assay of serum levels of total adiponectin (Bühlman, Basel, Switzerland), leptin (Quantikine; R&D Systems, Oxford, UK), and visfatin/NAMPT (Bühlman, Basel, Switzerland). "
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