Background B cell depletion therapy based on rituximab (RTX) is an effective therapy for Rheumatoid Arthritis (RA) and other autoimmune diseases such as Thrombotic Thrombocytopenic Purpura (TTP). Serum BAFF levels are within the normal range in patients with RA prior to RTX therapy, but are raised in TTP patients1. BAFF levels rise after RTX in both diseases and remain elevated for many months in the majority of patients. We have previously described lower percentages of naive and memory B cells expressing BAFFR at relapse following RTX2. Here, we have explored whether BAFFR expression after B cell repopulation was related to RTX treatment per se by comparing BAFFR expression in patients repopulated but remaining in remission in patients with RA or with TTP after RTX.
Objectives To compare expression of BAFFR in naive and memory B cells in TTP and RA patients in remission after RTX.
Methods Phenotype analysis of BAFFR expression on naive (CD27-) and memory (CD27+) B cells was performed using combinations of CD19 and CD27 in TTP patients (n:14) in remission after B cell repopulation following RTX and compared with patients with RA (n: 9) also in remission after RTX therapy. Mann Whitney U test was used to compare results.
Results The time of sampling following RTX ranged from 8 to 38 months in RA and 10 to 68 months in TTP. Phenotypic analysis showed similar proportions of naïve (CD27-) and memory (CD27+) B cells in both conditions. For naïve B cells, median was 93.5% (range 86.9-98.9%) for TTP and median 96.2% (range 66.0-98.8%) for RA. Similarly for memory B cells: median 6.1% (range 1.1-13.1%) for TTP and median 3.8% (range 1.2-34%) for RA. BAFFR expression on naive B cells from TTP patients was significantly higher with median 94.7% (range 29.4-99.7%) than RA median 52% (range 18.3-88%) (p=0. 01). For memory B cells, BAFFR% median levels were also higher for TTP patients: median 88.3% (range 40.8-97.8%) compared to RA patients median 42.2% (range 22.0-61.8%) (p<0.01). There was no correlation between the percentage of cells expressing BAFFR and months after RTX in either group.
Conclusions Repopulation of B cells after RTX follows similar patterns in patients with TTP and RA, mirroring ontogeny with naïve B cells predominating. However, BAFFR expression was significantly reduced following RTX in RA patients compared with patients with TTP. This was not related to the time elapsed following RTX. Downregulation of BAFFR expression on naïve B cell can occur following signalling through B cell receptor and toll-like receptor or in response to raised BAFF levels. The finding that BAFFR expression was lower in B cells in RA but not TTP patients after RTX suggests a disease specific dysregulation, consistent with an autoimmune phenotype already present in repopulating B cells.
B-cell activating factor is elevated in acute idiopathic thrombotic thrombocytopenic purpura. Thomas MR et al. Br J Haematol. 2011;155:620-2
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. De la Torre I et al. Ann Rheum Dis. 2010;69:2181-8
Disclosure of Interest None Declared
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