Altered Expression of CXCL13 and Its Chemokine Receptor CXCR5 on B Lymphocytes during Active Graves' Orbitopathy. (1st February 2021)

• Record Type: Journal Article
• Authors: Wan, Shangtao; Lin, Miaoli; Mao, Yuxiang; Chen, Xiaoqing; Liang, Dan
• Is Part Of: Current eye research. Volume 46:Number 2(2021)
• Page Start: 210
• Page End: 216
• Publication Date: 2021-02-01
• Subjects: Graves' orbitopathy -- CXCl13 -- CXCR5 -- B lymphocytes -- chemokine receptor; Ophthalmology -- Periodicals; Eye -- Diseases -- Periodicals; Ophthalmology -- Periodicals; 573.88
• DOI: 10.1080/02713683.2020.1786132
• Languages: English
• ISSNs: 0271-3683

Abstract

ABSTRACT: Purpose: To characterize the phenotypic abnormalities of peripheral B cells in patients with Graves' orbitopathy (GO) and explore the role of chemokine CXC ligand 13 and its receptor type 5 (CXCL13/CXCR5) in relation to B-cell homeostasis using specific neutralizing antibodies. Methods: Adults with active GO (n = 22), inactive GO (n = 28), and healthy control subjects (n = 28) were included in the study. Peripheral B cells and B-cell subsets were quantified and analyzed for CXCR5 expression by flow cytometry. The serum CXCL13 concentration was measured by enzyme-linked immunosorbent assays. For chemotactic experiments, Transwell plates were used, and migrating B cells were further analyzed by flow cytometry. Results: Compared to healthy subjects, patients with active GO had a significantly higher number of CD19 + B cells and the CD19 + CD27 + memory B-cell subset (P = .041 and P = .019, respectively), whereas a marginal increase in the number of these cells was found in patients with inactive GO (P = .062 and P = .087, respectively). Serum CXCL13 levels were significantly higher in patients with active GO (86.9 ± 30.4 pg/mL) than in those with inactive GO (41.7 ± 18.1 pg/mL; P < .001) and in healthy subjects (36.2 ± 7.8 pg/mL; P < .001). The increased CXCL13 concentration was positively and significantly correlated with the clinical activity score (r = 0.757, P < .001). Finally, serum from patients with active GO exerted a stronger chemotactic activity towards B cells and the CD19 + CD27 + memory B-cell subset. Blocking CXCL13 or CXCR5 with neutralizing antibodies reduced B-cell migration by a mean of 20%. Conclusions: Our data suggest that aberrant CXCL13/CXCR5 expression may contribute to the deficits in B-lymphocyte homeostasis observed in active GO.