Serum SmD autoantibody proteomes are clonally restricted and share variable-region peptides

M Al Kindi, Timothy Chataway, George Gilada, Michael Jackson, Fiona Goldblatt, Jennifer Walker, Alexander Colella, Thomas Gordon

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Recent advances in mass spectrometry-based proteomic methods have allowed variable (V)-region peptide signatures to be derived from human autoantibodies present in complex serum mixtures. Here, we analysed the clonality and V-region composition of immunoglobulin (Ig) proteomes specific for the immunodominant SmD protein subunit of the lupus-specific Sm autoantigen. Precipitating SmD-specific IgGs were eluted from native SmD-coated ELISA plates preincubated with sera from six patients with systemic lupus erythematosus (SLE) positive for anti-Sm/RNP. Heavy (H)- and light (L)-chain clonality and V-region sequences were analysed by 2-dimensional gel electrophoresis and combined de novo database mass spectrometric sequencing. SmD autoantibody proteomes from all six patients with SLE expressed IgG1 kappa restricted clonotypes specified by IGHV3-7 and IGHV1-69H-chains and IGKV3-20 and IGKV2-28L-chains, with shared and individual V-region amino acid replacement mutations. Clonotypic sharing and restricted V-region diversity of systemic autoimmunity can now be extended from the Ro/La cluster to Sm autoantigen and implies a common pathway of anti-Sm autoantibody production in unrelated patients with SLE.

    Original languageEnglish
    Pages (from-to)77-81
    Number of pages5
    JournalJournal of Autoimmunity
    Volume57
    DOIs
    Publication statusPublished - 2015

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