title: Secreted autoantibody repertoires in Sjögren's syndrome and systemic lupus erythematosus: A proteomic approach.
abstract: The structures of epitopes bound by autoantibodies against RNA-protein complexes have been well-defined over several decades, but little is known of the clonality, immunoglobulin (Ig) variable (V) gene usage and mutational status of the autoantibodies themselves at the level of the secreted (serum) proteome. A novel proteomic workflow is presented based on affinity purification of specific Igs from serum, high-resolution two-dimensional gel electrophoresis, and de novo and database-driven sequencing of V-region proteins by mass spectrometry. Analysis of anti-Ro52/Ro60/La proteomes in primary Sjögren's syndrome (SS) and anti-Sm and anti-ribosomal P proteomes in systemic lupus erythematosus (SLE) has revealed that these antibody responses are dominated by restricted sets of public (shared) clonotypes, consistent with common pathways of production across unrelated individuals. The discovery of shared sets of specific V-region peptides can be exploited for diagnostic biomarkers in targeted mass spectrometry platforms and for tracking and removal of pathogenic clones.
authors.affiliation: Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, 5042, South Australia, Australia.
authors.forename: Mahmood A
authors.initials: MA
authors.lastname: Al Kindi
authors.affiliation: Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, 5042, South Australia, Australia; Flinders Proteomic Facility, Flinders University, Australia.
authors.forename: Alex D
authors.initials: AD
authors.lastname: Colella
authors.affiliation: Flinders Proteomic Facility, Flinders University, Australia.
authors.forename: Tim K
authors.initials: TK
authors.lastname: Chataway
authors.affiliation: Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, 5042, South Australia, Australia.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Jackson
authors.affiliation: Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, 5042, South Australia, Australia. Electronic address: jing.wang@flinders.edu.au.
authors.forename: Jing J
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Immunology, Flinders Medical Centre and Flinders University, SA Pathology, Bedford Park, 5042, South Australia, Australia. Electronic address: t.gordon@flinders.edu.au.
authors.forename: Tom P
authors.initials: TP
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D020543:Proteome / Q000276:immunology; D040901:Proteomics; D012270:Ribosomes / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D020543:Proteome
keywords: Autoantibodies; Proteomic analysis; Sjögren's syndrome; Systemic lupus erythematosus