Long-term Ro60 humoral autoimmunity in primary Sjögren's syndrome is maintained by rapid clonal turnover

Rhianna Lindop, Georgia Arentz, Isabell Bastian, Andrew Whyte, Lauren Thurgood, Timothy Chataway, Michael Jackson, Thomas Gordon

    Research output: Contribution to journalArticlepeer-review

    14 Citations (Scopus)

    Abstract

    Long-term humoral autoimmunity to RNA-protein autoantigens is considered a hallmark of systemic autoimmune diseases. We use high resolution Orbitrap mass spectrometric autoantibody sequencing to track the evolution of a Ro60-specific public clonotypic autoantibody in 4 patients with primary Sjögren's syndrome. This clonotype is specified by a VH3-23/VK3-20 heavy and light chain pairing. Despite apparent stability by conventional immunoassay, analysis of V-region molecular signatures of clonotypes purified from serum samples collected retrospectively over 7years revealed sequential clonal replacement. Prospective longitudinal studies confirmed clonotype loss and replacement at approximately three-monthly intervals. Levels of secreted anti-Ro60 clonotypes fluctuated markedly over time, despite minimal changes in clonal affinity. Our novel findings indicate a relentless turnover of short-lived clonotypic variants, masquerading as long-lived Ro60 humoral autoimmunity.

    Original languageEnglish
    Pages (from-to)27-34
    Number of pages8
    JournalClinical Immunology
    Volume148
    Issue number1
    DOIs
    Publication statusPublished - 2013

    Keywords

    • Autoantibodies
    • Humoral autoimmunity
    • Mass spectrometry
    • Primary Sjögren's syndrome
    • Ro60

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