AB0194 BTLA EXPRESSION IS REDUCED ON SLE B CELL SUBSETS. (June 2019)

• Record Type: Journal Article
• Authors: Wiedemann, Annika; Stefanski, Ana-Luisa; Lino, Andreia; Dörner, Thomas
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 2
• Page Start: 1554
• Page End: 1554
• Publication Date: 2019-06
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2019-eular.4091
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: B- and T-lymphocyte attenuator (BTLA/CD272) is a co-receptor constitutively expressed on B cells [1, 2]. Upon B cell activation via the B cell receptor (BCR), BTLA co-localizes with Src homology region 2 domain-containing phosphatase-1 (SHP-1) and thus negatively regulates BCR signaling [2]. A recent study found that CD4+ T cells from SLE patients fail to upregulate BTLA upon activation [3], however, data on BTLA expression and function for B cells in autoimmunity is missing. Objectives: To assess BTLA expression on conventional naïve (CD20 + CD27 - ), conventional memory (CD20 + CD27 + ) B cells and on CD27 ++ CD38 ++ expressing plasma cells (PC) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) and healthy donors (HD). Methods: PBMCs were isolated from EDTA blood taken from 7 female SLE patients (age 38, mean disease activity 5 (SLEDAI)) and 6 female HD (mean age 28) by Ficoll density gradient centrifugation according to the manufacturer's protocol. Cells have been stained and expression of BTLA was assessed by flow cytometry. Results: Analysis of BTLA surface expression on B cell subsets in SLE patients and HD revealed decreased expression of BTLA on naïve SLE B cells (*p=0.0173, Mann-Whitney U Test (MWU), BTLA median fluorescence intensity (MFI) 9006±1450) compared to naïve HD B cells (11957±941). A similar tendency was found for memory SLE B cells (p=0.0823 MWU) compared to HD memory but not SLE PC and HD PC. Remarkably, an inverse correlation was found for BTLA expression on naïve SLE B cells and SLE PC with Siglec-1 expression on monocytes (*p=0.0333 Spearman's rank correlation (SRC) naïve B cells, *p=0.0167 PC), a marker for interferon signature, and the same trend was seen for SLE memory B cells (p=0.0583 SRC). Inverse correlation of BTLA expression was also found with disease activity (SLEDAI) with these B cell populations but did not reach significance (p=0.0583 naïve B cells, p=0.1361 memory B cells, p=0.0833 PC). Conclusion: Herein, we document that B cell subsets of SLE patients express lower levels of the negative regulator BTLA than HD. Additionally, an inverse correlation between BTLA expression on B cell subsets and Siglec-1 on monocytes were found suggesting its involvement in disease and consideration BTLA as therapeutic target in SLE. We hypothesize that reduced BTLA expression is a feature of post-activated B cells. Further studies need to delineate functional properties of BTLA expression and activation in autoimmune B cells. References: [1] Watanabe N, Gavrieli M, Sedy JR, Yang J, Fallarino F, Loftin SK, Hurchla MA, Zimmerman N, Sim J, Zang X, et al: BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat Immunol 2003, 4(7):670-679. [2] Vendel AC, Calemine-Fenaux J, Izrael-Tomasevic A, Chauhan V, Arnott D, Eaton DL: B and T lymphocyte attenuator regulates B cell receptor signaling by targeting Syk and BLNK. J Immunol2009, 182(3):1509-1517. [3] Sawaf M, Fauny JD, Felten R, Sagez F, Gottenberg JE, Dumortier H, Monneaux F: Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ T cells. JCI Insight 2018, 3(13). Disclosure of Interests: Annika Wiedemann: None declared, Ana-Luisa Stefanski: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Eli Lilly, Janssen, Roche, UCB Pharma, Consultant for: Eli Lilly, Janssen, Roche, UCB Pharma, Speakers bureau: Eli Lilly, Janssen