Background/Purpose: B-cell-activating-factor (BAFF) coordinates differentiation of B cells into immunoglobulin secreting cells (ISC) by binding to 3 different receptors (BBRs), namely BAFF-R, transmembrane activator and Calcium signal modulating cyclophilic ligand interactor (TACI) and B cell maturation antigen (BCMA). BAFF levels rise after B cell depletion therapy based on rituximab (BCDT) and remain raised in some patients at relapse. BAFF-R expression is reduced in relapsing patients after BCDT. We examined the level of BBR expression at relapse in relation to serum BAFF levels. 

Methods: BBRs % expression was examined on B cell sub-populations defined using combinations of CD19, CD38 and IgD. Serum BAFF levels were determined using a Human Quantikine^Ò BAFF/BLyS Immunoassay ELISA kit. We studied 10 Healthy Controls (HC), 10 RA patients before BCDT (Pre-BCDT) and 20 patients with RA at relapse, including 10 patients who had relapsed within 3 months after repopulation (Concordant Relapse: C-R) and 10 patients who had relapsed >3 months after repopulation (Discordant Relapse: D-R). 

Results: Following BCDT, BAFF levels rose and were significantly raised at relapse in both patient groups (C-R: median 2.19 ng/ml; 0.96-4.55, D-R: median 1.90 ng/ml; 1.14-6.47) when compared to HC (median 1.11 ng/ml; 0.89-1.24; p=0.02; p=0.002, respectively) and D-R only compared with patients pre-BCDT (1.39 ng/ml; 0.84-2.39; p=0.05). In the C-R group, 5/10 patients and in the D-R group 4/10 patients had BAFF levels > 2.4 ng/ml. In patients with raised BAFF levels, in all B cell subsets except plasmablasts,  %BAFF-R+ cells were significantly reduced compared with HC. % TACI+ cells were significantly reduced only in post-Germinal Center (GC) B cells in both relapsing patient cohorts. When serum BAFF levels were within normal limits, %BAFF-R+ transitional B cells in C-R patients were significantly lower than in D-R patients and HC, with other B cell populations following similar patterns as in total cohorts. %TACI positive cells remained significantly reduced in post-GC populations in D-R patients only, compared with HC. 

Conclusion: Patients with a C-R pattern of relapse maintained lower % BAFF-R+ B cells in transitional population compared with HC and D-R patients, independent of BAFF levels. This suggests that a proportion of this newly repopulating naïve B cell population is already committed to differentiation to ISC in patients with a concordant pattern of relapse. Reduced %TACI+ B cells in post-GC populations from D-R patients with normal BAFF levels may reflect a lack of up-regulation of TACI or downregulation due to internalisation or shedding of bound BAFF. Our results highlight probable differences in B cell biology in patients with different patterns of relapse following BCDT.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-baff-levels-and-relationship-with-baff-binding-receptors-in-patients-with-rheumatoid-arthritis-relapsing-after-b-cell-depletion-therapy/