Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2011-12, Vol.63 (12), p.3692-3701
• Main Authors: Sellam, Jérémie, Rouanet, Stéphanie, Hendel‐Chavez, Houria, Abbed, Karim, Sibilia, Jean, Tebib, Jacques, Le Loët, Xavier, Combe, Bernard, Dougados, Maxime, Mariette, Xavier, Taoufik, Yassine
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; B-Cell Activation Factor Receptor - metabolism; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - pathology; Biological and medical sciences; Case-Control Studies; Cross-Sectional Studies; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Female; Humans; Immunomodulators; Inflammatory joint diseases; Lymphocyte Depletion; Male; Medical sciences; Methotrexate - therapeutic use; Middle Aged; Pharmacology. Drug treatments; Predictive Value of Tests; Rituximab; Treatment Outcome; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.30599

Objective 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). Methods 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. Results Mean ± SD counts of both CD27− naive and CD27+ memory B cells were decreased in RA patients (188.6 ± 121.4/mm3) compared with controls (257.3 ± 154.1/mm3) (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). Conclusion 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.