Abstract
Objective: We evaluated the effects of the B-cell activating factor (BAFF)-targeting antibody Belimumab on human nonmemory B-cell pools. Human B-cell pools were identified using surface markers adapted from mouse studies that specifically assessed reductions in immature B cells due to BAFF depletion. Patients with systemic lupus erythematosus (SLE) have high levels of both BAFF and immature B cells. Mechanistic mouse studies provide a framework for understanding human responses to therapies that target B cells. Methods: Peripheral blood mononuclear cells were isolated from healthy donors and SLE patients on Belimumab or standard-of-care therapy (SCT). Cells were stained for flow cytometry to identify B-cell subsets based on CD21/CD24. Differences in subset proportions were determined by one-way ANOVA and Tukey’s post hoc test. Results: Patients treated with Belimumab show alterations in the nonmemory B-cell pool characterized by a decrease in the Transitional 2 (T2) subset (p = 0.002), and an increase in the proportion of Transitional 1 (T1) cells (p = 0.005) as compared with healthy donors and SCT patients. The naïve B-cell compartment showed no significant differences between the groups (p = 0.293). Conclusion: Using a translational approach, we show that Belimumab-mediated BAFF depletion reduces the T2 subset in patients, similar to observations in mouse models with BAFF depletion.
Original language | English |
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Pages (from-to) | 1337-1343 |
Number of pages | 7 |
Journal | Lupus |
Volume | 28 |
Issue number | 11 |
DOIs | |
State | Published - Oct 1 2019 |
ASJC Scopus Subject Areas
- Rheumatology
Keywords
- Belimumab
- human B-cell production
- systemic lupus erythematosus
- transitional B cells
- translational