B-cell Epitopes of Sjögren’s Syndrome-Related Autoantigens Ro/SSA and La/SSB

Abstract

A common laboratory finding in Sjogren's syndrome (SS) is the presence of autoantibodies against intracellular autoantigens. These autoantibodies usually target the Ro/La RNP complex, consisting of at least three proteins, the Ro52, La, and Ro60 autoantigens non-covalently associated with one of the four small, uridine-rich hY RNAs (human cYtoplasmic RNAs). In this review, we first provide a brief overview of the antigenic determinant types that have been identified on the corresponding autoantigens. The antibody targets of autoantigens include primary, secondary, tertiary, and quarternary structure epitopes as well as cryptotopes and neoepitopes. We next focus on the functional, structural, and antigenic features of the components of the Ro/La ribonucleoprotein particle and address the clinical value of the autoantibodies against them. We also discuss in detail the regulation of autoantibody production via idiotypic/anti-idiotypic network and the diversification of their specificity via epitope spreading. Finally, we describe the ability of post-translational modifications to induce autoreactive immune attack via the generation of neoepitopes and we summarize the potential of synthetic epitopes for future development of new diagnostic tests and novel therapeutic strategies.