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Publication Detail
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.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    de la Torre I, Moura RA, Leandro MJ, Edwards J, Cambridge G
  • Publication date:
    12/2010
  • Pagination:
    2181, 2188
  • Journal:
    Ann Rheum Dis
  • Volume:
    69
  • Issue:
    12
  • Status:
    Published
  • Country:
    England
  • PII:
    ard.2010.131326
  • Language:
    eng
  • Keywords:
    Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived, Antigens, CD19, Antirheumatic Agents, Arthritis, Rheumatoid, B-Cell Activating Factor, B-Lymphocyte Subsets, Cohort Studies, Humans, Immunologic Memory, Immunophenotyping, Lymphocyte Depletion, Middle Aged, Receptors, Interleukin-4, Recurrence, Rituximab, Treatment Outcome
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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