Secreted human Ro52 autoantibody proteomes express a restricted set of public clonotypes
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Date
Dec-12, 2012-12-01
Authors
Arentz, Georgia
Thurgood, Lauren Alexandra
Lindop, Rhianna
Chataway, Timothy Kennion
Gordon, Thomas Paul
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Rights
Copyright 2012 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.
Rights Holder
Elsevier Ltd.
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.
Description
This article appeared in a journal published by Elsevier Ltd. Under Elsevier's copyright, mandated authors are not permitted to make work available in an institutional repository.
Keywords
Autoimmunity, Proteome, Autoantibodies
Citation
Arentz, G., Thurgood, L.A., Lindop, R., Chataway, T.K. and Gordon, T.P., 2012. Secreted human Ro52 autoantibody proteomes express a restricted set of public clonotypes. Journal of Autoimmunity, 39(4), 466-470.