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 13 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. Conclusion. 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.