Session Information
Date: Monday, November 9, 2015
Title: B cell Biology and Targets in Rheumatolid Arthritis and other Autoimmune Disease Poster
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: The B cell pool is composed of subsets with different phenotypes and functions that mainly have effector functions to maintain immunologic tolerance. These subsets and their proportions are an individual’s “B cell signature” (BCS). Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease. BCS SLE studies reveal altered immature and unswitched memory B cell numbers when compared to healthy controls (HC). BCS potentially can be a biomarker for monitoring SLE disease activity. Belimumab is B-cell activating factor inhibitor approved for use in SLE. For this study, we will determine the effect of belimumab on BCS in SLE patients.
Methods: PBMCs and plasma were collected from 5 SLE patients on belimumab, 13 SLE patients conventional non-B cell-standard therapy (ST) and 12 HC. Demographic data, medication history, disease activity and damage measurements were collected. B cell subsets including transitional, naive and memory were assessed using 7-color flow cytometry and Flowjo Analysis software. Plasma BAFF levels were evaluated using ELISA. Subset percentages within the B cell pool (CD19+) and BAFF levels were correlated with clinical parameters. Student t test to analyze differences between groups was used.
Results: Altered BCS in belimumab patients were observed. CD21/CD24 co-expression model for nonmemory subsets showed significant increase in T1 cells (P < 0.001) while T2 cells were significantly decreased (P < 0.0001) in HC and belimumab groups. When comparing HC to ST, a significant decrease in T2 cells comparable to belimumab was noted. Number of T2 derived naïve cells between HC and SLE was not significant. A significant difference in the number of naive cells between belimumab and ST (P < 0.01) was noted. Using IgD/CD27 co-expression to evaluate memory subsets, significant decreases in unswitched memory cells (IgD+) in both ST and belimumab compared to HC (P < 0.01), respectively, was noted. Assessment of switched memory cells showed significant decreases (P > 0.01) in ST compared to HC, yet belimumab displayed a significant increase (P > 0.01) in switched memory cells compared to ST. Assessment of double negative memory (CD27neg) noted a significant increase in belimumab compared to HC (P > 0.01).
Conclusion: This is the first clinical belimumab study using the translational model CD21/CD24 to thoroughly evaluate B cell subsets for BCS. The model was derived from mouse studies evaluating the effect of BAFF on T1 and T2 in promoting the development of auto-reactive naive B cells. Evaluating the effect of belimumab on BCS can serve as a biomarker for patient response. Individual BCS may also allow clinicians to tailor a treatment regimen in either induction and/or maintenance therapy that is specific to their patients in the future.
To cite this abstract in AMA style:
Ngo MT, Benitez A, Payne KJ, De Vera M, Milford TA, Torralba KMD. B Cell Signature Profiling in Systemic Lupus Erythematosus Patients on Belimumab [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/b-cell-signature-profiling-in-systemic-lupus-erythematosus-patients-on-belimumab/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-cell-signature-profiling-in-systemic-lupus-erythematosus-patients-on-belimumab/