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.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
de la Torre
Inmaculada
I
Rheumatology Department, University College London, London, UK.
Moura
Rita A
RA
Leandro
Maria J
MJ
Edwards
Jonathan
J
Cambridge
Geraldine
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D018941:Antigens, CD19 / Q000097:blood; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D053264:B-Cell Activating Factor / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015331:Cohort Studies; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008212:Lymphocyte Depletion / Q000379:methods*; D008875:Middle Aged; D019948:Receptors, Interleukin-4 / Q000097:blood*; D012008:Recurrence; D000069283:Rituximab; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018501:Antirheumatic Agents; D053264:B-Cell Activating Factor; D019948:Receptors, Interleukin-4; D000069283:Rituximab