Background/Purpose: Insight into B cell subset dynamics and homeostasis can provide a biological rationale for use of B cell targeted therapies in SLE patients. Using our B cell signature (BCS) approach we wanted to assess whether treatment with Belimumab would result in a unique BCS that reflects a reduction in B cell subsets that are most sensitive to B cell activating factor (BAFF) depletion. Our BCS used the CD21/CD24 model that delineates analogous mouse and human nonmemory B cell subsets. Mouse studies have used CD21 and CD24 co-expression to identify which subsets are susceptible to BAFF depletion.

Methods: PBMCs were isolated from healthy donors, and SLE patients on Belimumab or standard of care therapy (SCT). Cells were stained for flow cytometry to identify nonmemory and memory subsets. BCS were determined based on the frequency of each B cell subsets within the nonmemory and memory pools and compared across treatment groups. One-way ANOVA test and Tukey’s post-hoc test were used for statistical analysis.

Results: Our evaluation of BCS showed that Belimumab (n=13) patients had significantly higher proportions of nonmemory transitional 1 cells (p = 0.0062) compared to SCT (n=24) patients and healthy controls (n=14). Alternately, Belimumab patients had significantly lower proportions of nonmemory transitional 2 subset (p=0.0014) compared to healthy controls. FM (naïve) cells displayed no significant differences between the three groups. When we assessed the ratio of T1 to T2, Belimumab B cells had a larger ratio compared to both healthy and SCT (p=0.0033), but healthy and SCT were not significantly different. We also evaluated total transitional B cells to FM cells and noted no significant differences.

Conclusion: Our results show that B cell subsets must be stringently assessed as indicated by the transitional B cell subset data. BCS from Belimumab patients display unique profiles compared to both SCT and healthy donors. Our future studies will consist of a longitudinal evaluation of BCS in pre-Belimumab treatment and at subsequent time points in order to correlate BCS alterations with specific patient clinical characteristics.

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/nonmemory-b-cell-signature-alterations-in-belimumab-patients/