Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis.
OBJECTIVE
To study the quantitative and phenotypic reconstitution of peripheral blood B cells and its relationship to the dynamics of clinical response in patients with rheumatoid arthritis (RA) following B cell depletion with rituximab.


METHODS
Twenty-four patients with active RA treated with rituximab were studied. Flow cytometry with combinations of monoclonal antibodies to B cell and T cell subsets was used.


RESULTS
The frequency and total number of CD19+ cells in the peripheral blood decreased a mean of 97% for more than 3 months in all but 1 patient following rituximab therapy. All B cell populations were depleted. More than 80% of residual B cells showed a memory or plasma cell precursor phenotype. B cell repopulation occurred a mean of 8 months after treatment and was dependent on the formation of naive B cells, which showed an increased expression of CD38 and CD5. During repopulation, increased numbers of circulating immature B cells, CD19+,IgD+,CD38(high),CD10(low),CD24(high) cells, were identified. Patients who experienced a relapse of RA on return of B cells tended to show repopulation with higher numbers of memory B cells. A small number of T cells and natural killer cells expressed low levels of CD20. These cells were depleted following rituximab therapy and returned to the circulation a mean of 5 months after treatment. No other significant changes were detected in the T cell populations studied.


CONCLUSIONS
Rituximab induced a profound depletion of all peripheral blood B cell populations in patients with RA. Repopulation occurred mainly with naive mature and immature B cells. Patients whose RA relapsed on return of B cells tended to show repopulation with higher numbers of memory B cells.
Leandro
Maria J
MJ
University College London, Center for Rheumatology, London, UK. maria.leandro@ucl.ac.uk
Cambridge
Geraldine
G
Ehrenstein
Michael R
MR
Edwards
Jonathan C W
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000032:analysis; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D018501:Antirheumatic Agents; D000069283:Rituximab