P034 Cell surface sialylation of B-cell subsets from patients with rheumatoid arthritis. (21st February 2018)

• Record Type: Journal Article
• Authors: Johnston, L; Ouboussad, L; Aslam, A; Buch, MH
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 1
• Page Start: A27
• Page End: A27
• Publication Date: 2018-02-21
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-EWRR2018.56
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Introduction: B-cells have a well-established role in the pathogenesis of rheumatoid arthritis (RA), illustrated by the successful treatment of RA with B-cell depletion therapy. 1 Sialic acid (SA) is a 9-carbon backbone sugar involved in many immune system functions including cell migration, adhesion and activation. 2 In RA, sialylation of the B-cell surface, including membrane bound IgM, has been found to differ from healthy control B-cells. These changes have been attributed to alterations in antibody glycosylation which lead to the highly inflammatory phenotype of disease-specific autoantibodies. 3 Recently it has been shown that surface glycosylation of regulatory T-cells is altered by activating stimuli – suggesting functional consequences for cell surface glycans. 4 Functional effects of surface glycans in B-cells in RA have not been well established. Objectives: The aim of this study is to investigate surface sialylation of B-cells from patients with RA at different stages of disease, and to examine functional consequences of B-cell surface sialylation. Methods: Sialylation of peripheral blood mononuclear cells isolated from 7 patients with either 'pre-RA' or RA (3 patients with ACPA+ 'pre-RA', 1 patient with a diagnosis of new onset, ≤12 months symptom duration, and 3 patients with established disease) was analysed by flow cytometry using biotinylated Sambucus Nigra (SNA) Lectin, to bind to α2, 6 SA, with PE-conjugated streptavidin. MESF beads were used to standardise the measurement of fluorescence intensity. B-cells were activated in culture with anti-CD40 and anti-IgM. Results: Initial data suggests that B-cell surface sialylation may be higher in patients with pre-RA (MESF: 13765±170) or new onset RA (13094) than in patients with established RA (12431.3±339). Sialylation also tended to be higher on plasmablasts (1396±991) than on memory (13067±496) or naïve B-cells (13127±710). Upon in vitro activation with anti-CD40 and anti-IgM, sialylation tended to decrease in plasmablasts (20042±679 vs 16200.5±1261). Conclusions: Preliminary results suggest that B-cell surface sialylation may vary according to stage of disease and B-cell subset. Sialylation may also be related to B-cell activation. Further investigations will be carried out to better understand variations in surface sialic acid and examine the relationship between B-cell function and surface sialylation. References: . Mok CC. Drug Des Devel Ther2014;8:87–100. . Varki A, Gagneux P. Ann N Y Acad Sci2012;1253(1):16–36. . Pfeifle R, et al. Nature Immunology2017;18:1. . Cabral J, et al. Frontiers in Immunology2017;8:987. Disclosure of interest: None declared