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

Autoimmunity Reviews
Mahmood A Al KindiTom P Gordon

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.

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Citations

Oct 6, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alexander ShlemovPavel A Pevzner
Aug 8, 2018·Clinical and Experimental Immunology·J J WangT P Gordon
Jul 22, 2020·Arthritis & Rheumatology·Jing J WangMihir D Wechalekar
May 31, 2017·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Apr 3, 2018·Rheumatology·Katherine JamesUNKNOWN UK Primary Sjögren’s Syndrome Registry
May 11, 2021·Frontiers in Immunology·Manuel Sáez MoyaPablo Engel

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