title: Secreted human Ro52 autoantibody proteomes express a restricted set of public clonotypes.
abstract: Long-lived secreted autoantibody responses in systemic autoimmunity are generally regarded to be polyclonal and to express a diverse B-cell repertoire. Here, we have used a proteomic approach based on de novo sequencing to determine the clonality and V region structures of human autoantibodies directed against a prototypic systemic autoantigen, Ro52 (TRIM21). Remarkably, anti-Ro52 autoantibodies from patients with primary Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis or polymyositis were restricted to two IgG1 kappa clonotypes that migrated as a single species on isoelectric focusing; shared a common light chain paired with one of two closely-related heavy chains; and were public in unrelated patients. Targeted mass spectrometry using these uniquely mutated V region peptides as surrogates detected anti-Ro52 autoantibodies in human sera with high sensitivity and specificity compared with traditional ELISA. Mass spectrometry-based detection of specific autoantibody motifs provides a powerful new tool for analysis of humoral autoimmunity.
authors.affiliation: Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Flinders Drive, Bedford Park, 5042 South Australia, Australia.
authors.forename: Georgia
authors.initials: G
authors.lastname: Arentz
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Thurgood
authors.forename: Rhianna
authors.initials: R
authors.lastname: Lindop
authors.forename: Tim K
authors.initials: TK
authors.lastname: Chataway
authors.forename: Tom P
authors.initials: TP
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000097:blood / Q000235:genetics / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000097:blood / Q000235:genetics / Q000276:immunology*; D007525:Isoelectric Focusing; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D020543:Proteome / Q000235:genetics / Q000276:immunology*; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology*; D012680:Sensitivity and Specificity; D012859:Sjogren's Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D000099207:SS-A Antigen
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007145:Immunoglobulin kappa-Chains; D010455:Peptides; D020543:Proteome; D012261:Ribonucleoproteins; D000099207:SS-A Antigen