Background/Purpose: B cell depletion therapy based on rituximab (RTX) is an effective therapy for Rheumatoid Arthritis (RA) and for Thrombotic Thrombocytopenic Purpura (TTP). Serum B cell activating factor (BAFF) levels are within normal limits in patients with RA prior to RTX therapy, but may be raised in TTP. BAFF levels rise after RTX in both diseases. Nearly all mature B cells express BAFF-receptor (BAFF-R) in normal individuals. We have previously described lower % of na•ve and memory B cells expressing BAFF-R in RA at relapse following RTX. Here, we present B cell phenotypes and %BAFF-R+ve cells in TTP patients at repopulation and in both diseases in repopulated patients in remission after RTX. Results were also analyzed in relation to serum BAFF levels.

Methods:   Phenotypes and %BAFF-R+ve naive (CD27-) (NB) and memory (CD27+) (MB) B cells were performed using FACS analysis. Healthy controls (HC), patients with TTP, either repopulating or in remission were compared with RA repopulated patients remaining in remission after RTX (Mann Whitney U test).

Results: Median time to repopulation in TTP patients was 6 months, range 4-7. Time of sampling after RTX in repopulated patients ranged from 8-38 months in RA remission patients and 10-68 months in TTP remission patients. In remission, NB cells remained high with slow regeneration of MB in both RA and TTP. As previously shown in RA, % BAFFR +ve cells in TTP were low at repopulation in both NB and MB cells. However, % BAFFR +ve cells reached normal levels in TTP patients remaining in remission months after repopulation, but stayed low in patients with RA, independent of time after last RTX cycle or number of cycles. BAFF levels remained elevated in RA patients in remission as opposed to TTP. There was a significant inverse correlation between BAFF levels and % BAFF-R +ve NB and MB cells in TTP patients in remission (p<0.001; r²>0.70 in both) but not in patients with RA.

*p <0.01

**p<0.05

Conclusion: Repopulation of B cells after RTX follows similar patterns in patients with TTP and RA, with na•ve B cells predominant. The finding that %BAFF-R+ve B cells was lower in remission in RA but not in TTP after RTX suggests a disease specific dysregulation, consistent with an autoimmune phenotype already present in repopulating B cells.