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Pathogenicity and proteomic signatures of autoantibodies to Ro and La
Author(s) -
Lindop Rhianna,
Arentz Georgia,
Thurgood Lauren A,
Reed Joanne H,
Jackson Michael W,
Gordon Tom P
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.108
Subject(s) - autoantibody , ribonucleoprotein , autoimmunity , immunology , biology , immune system , antigen , antibody , genetics , rna , gene
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.