title: Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis.
abstract: 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/mm(3)) compared with controls (257.3 ± 154.1/mm(3)) (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).
  
  
  CONCLUSIONS
  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.
authors: Hôpital Bicêtre, AP-HP, INSERM U1012, and Université Paris-Sud 11, Le Kremlin Bicêtre, France. jeremie.sellam@sat.aphp.fr
authors: Jérémie
authors: J
authors: Sellam
authors: Stéphanie
authors: S
authors: Rouanet
authors: Houria
authors: H
authors: Hendel-Chavez
authors: Karim
authors: K
authors: Abbed
authors: Jean
authors: J
authors: Sibilia
authors: Jacques
authors: J
authors: Tebib
authors: Xavier
authors: X
authors: Le Loët
authors: Bernard
authors: B
authors: Combe
authors: Maxime
authors: M
authors: Dougados
authors: Xavier
authors: X
authors: Mariette
authors: Yassine
authors: Y
authors: Taoufik
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011237:Predictive Value of Tests; D000069283:Rituximab; D016896:Treatment Outcome; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D053265:B-Cell Activation Factor Receptor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000069283:Rituximab; D008727:Methotrexate