title: Long-term Ro60 humoral autoimmunity in primary Sjögren's syndrome is maintained by rapid clonal turnover.
abstract: Long-term humoral autoimmunity to RNA-protein autoantigens is considered a hallmark of systemic autoimmune diseases. We use high resolution Orbitrap mass spectrometric autoantibody sequencing to track the evolution of a Ro60-specific public clonotypic autoantibody in 4 patients with primary Sjögren's syndrome. This clonotype is specified by a VH3-23/VK3-20 heavy and light chain pairing. Despite apparent stability by conventional immunoassay, analysis of V-region molecular signatures of clonotypes purified from serum samples collected retrospectively over 7years revealed sequential clonal replacement. Prospective longitudinal studies confirmed clonotype loss and replacement at approximately three-monthly intervals. Levels of secreted anti-Ro60 clonotypes fluctuated markedly over time, despite minimal changes in clonal affinity. Our novel findings indicate a relentless turnover of short-lived clonotypic variants, masquerading as long-lived Ro60 humoral autoimmunity.
authors: Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, 5042, South Australia, Australia.
authors: Rhianna
authors: R
authors: Lindop
authors: Georgia
authors: G
authors: Arentz
authors: Isabell
authors: I
authors: Bastian
authors: Andrew F
authors: AF
authors: Whyte
authors: Lauren A
authors: LA
authors: Thurgood
authors: Tim K
authors: TK
authors: Chataway
authors: Michael W
authors: MW
authors: Jackson
authors: Tom P
authors: TP
authors: Gordon
mesh_terms: D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D002999:Clone Cells; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D013058:Mass Spectrometry; D008875:Middle Aged; D011446:Prospective Studies; D020733:RNA, Small Cytoplasmic / Q000097:blood / Q000276:immunology*; D012189:Retrospective Studies; D012261:Ribonucleoproteins / Q000097:blood / Q000276:immunology*; D020539:Sequence Analysis, Protein; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D000099207:SS-A Antigen
chemical_list: D001324:Autoantigens; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; C116006:RO60 protein, human; D000099207:SS-A Antigen