Secreted human Ro52 autoantibody proteomes express a restricted set of public clonotypes
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Thurgood, Lauren Alexandra
Chataway, Timothy Kennion
Gordon, Thomas Paul
Copyright 2012 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.
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.
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.
Autoimmunity, Proteome, Autoantibodies
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.