Secreted human Ro52 autoantibody proteomes express a restricted set of public clonotypes

Timothy Chataway, Georgia Arentz, Lauren Thurgood, Rhianna Lindop, Tom Gordon

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)466-470
    Number of pages5
    JournalJournal of Autoimmunity
    Volume39
    Issue number4
    DOIs
    Publication statusPublished - 2012

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