Anti-topoisomerase, but not anti-centromere B cell responses in systemic sclerosis display active, Ig-secreting cells associated with lung fibrosis

Autor: Jeska De Vries-Bouwstra, Tom WJ Huizinga, René EM Toes, Hans U Scherer, Maaike Boonstra, Cynthia M Fehres, Corrie M Wortel, Sophie IE Liem, Nina M van Leeuwen, Lauran Stöger
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: RMD Open, Vol 9, Iss 3 (2023)
Druh dokumentu: article
ISSN: 2056-5933
DOI: 10.1136/rmdopen-2023-003148
Popis: Objectives Almost all patients with systemic sclerosis (SSc) harbour autoantibodies. Anti-topoisomerase antibodies (ATA) and anti-centromere antibodies (ACA) are most prevalent and associate with distinct clinical phenotypes. B cell responses underlying these phenotypes are ill-defined. To understand how B cell autoreactivity and disease pathology connect, we determined phenotypic and functional characteristics of autoreactive B cells in ATA-positive and ACA-positive patients.Methods Levels and isotypes of autoantibodies secreted by ex vivo cultured peripheral blood mononuclear cells from patients with ATA-positive (n=22) and ACA-positive (n=20) SSc were determined. Antibody secreting cells (ASCs) were isolated by cell sorting and cultured separately. Correlations were studied between the degree of spontaneous autoantibody production and the presence and degree of interstitial lung disease (ILD).Results Circulating B cells secreting either ATA-immunoglobulin G (IgG) or ACA-IgG on stimulation was readily detectable in patients. The ATA response, but not the ACA response, showed additional secretion of autoreactive IgA. ATA-IgG and ATA-IgA were also secreted spontaneously. Additional cell sorting confirmed the presence of ATA-secreting plasmablasts. The degree of spontaneous ATA-secretion was higher in patients with ILD than in those without (p
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