Secreted autoantibody repertoires in Sjögren's syndrome and systemic lupus erythematosus: A proteomic approach

Mahmood Al Kindi, Alexander Colella, Timothy Chataway, Michael Jackson, Jing J Wang, Thomas Gordon

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    The structures of epitopes bound by autoantibodies against RNA-protein complexes have been well-defined over several decades, but little is known of the clonality, immunoglobulin (Ig) variable (V) gene usage and mutational status of the autoantibodies themselves at the level of the secreted (serum) proteome. A novel proteomic workflow is presented based on affinity purification of specific Igs from serum, high-resolution two-dimensional gel electrophoresis, and de novo and database-driven sequencing of V-region proteins by mass spectrometry. Analysis of anti-Ro52/Ro60/La proteomes in primary Sjögren's syndrome (SS) and anti-Sm and anti-ribosomal P proteomes in systemic lupus erythematosus (SLE) has revealed that these antibody responses are dominated by restricted sets of public (shared) clonotypes, consistent with common pathways of production across unrelated individuals. The discovery of shared sets of specific V-region peptides can be exploited for diagnostic biomarkers in targeted mass spectrometry platforms and for tracking and removal of pathogenic clones.

    Original languageEnglish
    Pages (from-to)405-410
    Number of pages6
    JournalAUTOIMMUNITY REVIEWS
    Volume15
    Issue number4
    DOIs
    Publication statusPublished - 2016

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