Pathogenicity and proteomic signatures of autoantibodies to Ro and La

Rhianna Lindop, Georgia Arentz, Lauren Thurgood, Joanne Reed, Michael Jackson, Thomas Gordon

    Research output: Contribution to journalArticlepeer-review

    26 Citations (Scopus)

    Abstract

    Ro/SSA and La/SSB comprise a linked set of autoantigens that are clinically important members of the extractable nuclear antigen family and key translational biomarkers for lupus and primary Sjögren's syndrome. Autoantibodies directed against the Ro60 and La polypeptide components of the Ro/La ribonucleoprotein complex, and the structurally unrelated Ro52 protein, mediate tissue damage in the neonatal lupus syndrome, a model of passively acquired autoimmunity in humans in which the most serious manifestation is congenital heart block (CHB). Recent studies have concentrated on two distinct pathogenic mechanisms by which maternal anti-Ro/La autoantibodies can cause CHB: by forming immune complexes with apoptotic cells in developing fetal heart; and/or by acting as functional autoantibodies that cross-react with and inhibit calcium channels. Although the precise role of the individual autoantibodies is yet to be settled, maternal anti-Ro60 and anti-Ro52 remain the most likely culprits. This article will discuss the molecular pathways that culminate in the development of CHB, including the recent discovery of β2 glycoprotein I as a protective factor, and present a proteomic approach based on direct mass spectrometric sequencing, which may give a more representative snapshot of the idiotype repertoire of these autoantibodies than genomic-based technologies.

    Original languageEnglish
    Pages (from-to)304-309
    Number of pages6
    JournalImmunology and Cell Biology
    Volume90
    Issue number3
    DOIs
    Publication statusPublished - Mar 2012

    Keywords

    • anti-Ro/La autoantibodies
    • autoantibody proteome
    • congenital heart block
    • systemic autoimmune diseases

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