Open Access Open Badges Research article

High levels of memory B cells are associated with response to a first tumor necrosis factor inhibitor in patients with rheumatoid arthritis in a longitudinal prospective study

Claire I Daien1234*, Sarah Gailhac2, Thibault Mura5, Bernard Combe13, Michael Hahne246 and Jacques Morel1234

Author Affiliations

1 Department of Rheumatology, Lapeyronie Teaching Hospital, Av.Doyen Gaston Giraud, 34295, Montpellier, France

2 Molecular Genetic Institut of Montpellier, CNRS, UMR5535, 1919 route de Mende, 34090 Montpellier, France

3 Montpellier I university, 39 Rue Université, Montpellier, France

4 Montpellier II university, 2 Place Eugène Bataillon, 34095 Montpellier, France

5 Clinical investigation center, Saint Eloi Hospital, 80, avenue Augustin FLICHE, 34295 Montpellier, France

6 Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands

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Arthritis Research & Therapy 2014, 16:R95  doi:10.1186/ar4543

Published: 15 April 2014



Tumor necrosis factor inhibitor (TNFi) therapy is effective for rheumatoid arthritis (RA). Some researchers have suggested that TNFi therapy affects B-cell homeostasis. We studied the effect of TNFi therapy on the distribution of peripheral B-cell subsets to elucidate B-cell–related biomarkers to predict the TNFi response.


Peripheral B cells were analyzed for expression of CD19, CD27, CD38 and immunoglobulin D in 31 healthy donors and 96 RA patients, including 21 patients who were followed 3 months after TNFi initiation.


Treatment with steroids significantly altered the distribution of B-cell subsets. After we adjusted for age, sex and steroid dose, we found that patients with RA had B-cell subset proportions similar to controls. B-cell subset distributions did not differ upon use of TNFi at baseline or before or after TNFi introduction. TNFi responders (according to European League Against Rheumatism criteria) at 3 months had significantly higher proportions of CD27+ memory B cells at baseline, and ≥26% CD27+ cells at inclusion was associated with a relative risk of 4.9 (1.3 to 18.6) for response to TNFi treatment. CD27+ cells produced three times more TNFα than did TNFi-naïve B cells and were correlated with interferon γ produced from CD4+ cells in patients without TNFi treatment.


In patients with RA, high levels of baseline memory B cells were associated with response to TNFi, which may be related to TNFα-dependent activation of the T helper type 1 cell pathway.