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B-cell-activating factor receptor expression on naive and memory B cells: relationship with relapse in patients with rheumatoid arthritis following B-cell depletion therapy
  1. Inmaculada de la Torre1,2,
  2. Rita A Moura3,
  3. Maria J Leandro1,
  4. Jonathan Edwards1,
  5. Geraldine Cambridge1
  1. 1Rheumatology Department, University College London, London, UK
  2. 2Rheumatology Department, Gregorio Maranon Hospital, Madrid, Spain
  3. 3Rheumatology Department, Instituto de Biologia Molecular, Lisbon, Portugal
  1. Correspondence to Dr Geraldine Cambridge, Department of Medicine, Center for Rheumatology, Universty College London, Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK; g.cambridge{at}ucl.ac.uk

Abstract

Objectives To examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27− and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab.

Patients and Methods BAFF-R expression on B-cell subsets was determined in normal controls (NC; n=11), active patients with RA pre-rituximab (pre-RX; n=15), relapsing patients either concordant for B-cell repopulation (C-R, n=13) or discordant, with relapse more than 3 months after repopulation (D-R, n=11) and patients in remission over 3 months postrepopulation (discordant non-relapsing (D-NR), n=5). Serum BAFF was measured by ELISA and analysed using Mann–Whitney.

Results There was no significant difference between NC, pre-RX and D-NR patients in %BAFF-R-positive B cells or mean fluorescence intensity (MFI) in naive and memory B cells. Relapsing patients had significantly lower MFI and %BAFF-R-positive cells in both naive and memory compartments from NC and pre-RX (C-R and D-R; p<0.01). BAFF levels in pre-RX patients were within the normal range and did not correlate with BAFF-R expression in any patient group. D-NR patients had relatively lower proportions of pre and postswitch CD27+ B cells than pre-RX patients (D-NR vs pre-RX; p<0.05 for both) and also lower numbers of postswitch B cells than D-R patients (D-NR vs D-R, p<0.05).

Conclusion BAFF-R expression was significantly reduced on both naive and memory B cells in patients at relapse, regardless of the relationship with B-cell repopulation or serum BAFF levels. Re-establishment of active disease was also associated with an increase in class-switch recombination. Factors responsible for lower levels of BAFF-R may relate to altered thresholds for autoreactive B-cell generation at relapse in patients with RA.

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Footnotes

  • Funding The authors wish to thank the Worshipful Company of Grocers of the City of London for their generous support. RAM was supported by a grant from Fundação para a Ciência ea Tecnologia SFRH/BD/30247/2006 and IDLTO by the Alonso Martin Escudero Foundation.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the University College Hospitals London Ethics Committee.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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