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IgV peptide mapping of native Ro60 autoantibody proteomes in primary Sjogren's syndrome reveals molecular markers of Ro/La diversification

Abstract

We have used high-resolution mass spectrometry to sequence precipitating anti-Ro60 proteomes from sera of patients with primary Sjögren's syndrome and compare immunoglobulin variable-region (IgV) peptide signatures in Ro/La autoantibody subsets. Anti-Ro60 were purified by elution from native Ro60-coated ELISA plates and subjected to combined de novo amino acid sequencing and database matching. Monospecific anti-Ro60 Igs comprised dominant public and minor private sets of IgG1 kappa and lambda restricted heavy and light chains. Specific IgV amino acid substitutions stratified anti-Ro60 from anti-Ro60/La responses, providing a molecular fingerprint of Ro60/La determinant spreading and suggesting that different forms of Ro60 antigen drive these responses. Sequencing of linked anti-Ro52 proteomes from individual patients and comparison with their anti-Ro60 partners revealed sharing of a dominant IGHV3-23/IGKV3-20 paired clonotype but with divergent IgV mutational signatures. In summary, anti-Ro60 IgV peptide mapping provides insights into Ro/La autoantibody diversification and reveals serum-based molecular markers of humoral Ro60 autoimmunity.

Type Journal
Authors Wang, J. J.; Al Kindi, M. A.; Colella, A. D.; Dykes, L.; Jackson, M. W.; Chataway, T. K.; Reed, J. H.; Gordon, T. P.;
Publisher Name CLINICAL IMMUNOLOGY
Published Date 2016-12-01
Published Volume 173
Published Pages 57-63
Status Published in-print
URL link to publisher's version http://www.ncbi.nlm.nih.gov/pubmed/27609500
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/13511