Chapter 15 - Extractable Nuclear Antigens and SLE: Specificity and Role in Disease Pathogenesis

Abstract

Autoantibodies directed against specific nuclear antigens (proteins and DNA) are central to the pathogenesis of systemic lupus erythematosus (SLE). Anti-extractable nuclear antigens (ENA) antibodies are detected to varying degrees in SLE patients. Knowledge regarding the genetic susceptibility towards developing SLE and the etiology of autoantibody development has greatly increased in recent years and it is now widely accepted that defective clearance of apoptotic bodies, viral infection, and molecular mimicry all contribute to the activation of autoreactive B cells and autoantibody production. Anti-ENA antibodies develop a number of years prior to disease onset and, with the exception of Anti-Ro and anti-Sm, are not directly implicated in tissue pathogenesis. The role of the IFN system in the pathophysiology of SLE is well recognized. The anti-ENA immune complexes, by virtue of their being bound to RNA, act as potent stimulators of TLR7 and help drive IFN-α production by plasmacytoid dendritic cells and promote the autoimmune cycle. Recent research findings have suggested that a subset of ENA autoantigens, associated with the Ro/La autoantigen complex, is potentially involved in regulating IFN responses and innate immune detection mechanisms. The possibility that autoantibody generation not only mediates inflammation associated with the recognition of autoantigens but might also result in the inappropriate sequestering of Ro52 and Ro60 is being probed into.