Autoimmunity: Ro60-associated RNA takes its toll on disease pathogenesis.
The 60 kDa SSA/Ro (Ro60) ribonucleoprotein is a clinically important member of the extractable nuclear antigen family and a frequent target of humoral autoimmunity in individuals with systemic lupus erythematosus (SLE) or primary Sjögren syndrome and in mothers of children with neonatal lupus. The striking association between anti-Ro60 autoantibodies and inflammatory sequelae in these diseases has led to the hypothesis that the RNA-binding properties of Ro60 give rise to aberrant Toll-like receptor (TLR) signalling. As such, identification of the Ro60-associated RNA that ligates the endosomal RNA-recognizing receptors TLR7 and TLR8 could provide novel therapeutic targets. A new study by Hung et al.1 lends support to this hypothesis and suggests that endogenous retroelements could have a role in Ro60-related autoimmunity. Hung et al.1 catalogued Ro60-bound RNA in two human cell lines—an Epstein–Barr virus (EBV)-transformed B-cell line and an erythromyeloblastoid leukaemia cell line—and identified an extensive array of transcripts, which included common repetitive transposons termed Alu retroelements. Transfection of Alu elements into human peripheral blood mononuclear cells (PBMCs) stimulated secretion of proinflammatory cytokines. Moreover, Alu retroelement expression was increased in sera from patients with SLE relative to controls, particularly those with high interferon signature metric (ISM) scores1. Although these findings establish a link between Alu retroelements and type I interferon, relevance to anti-Ro60 autoantibody-mediated tissue injury is not as clear, and the potential for Alu elements and other Ro60-associated RNAs to stimulate TLR7 and TLR8 in a physiological setting warrants further investigation.
|Authors||Reed,JH; Gordon, TP.|
|Responsible Garvan Author|
|Publisher Name||Nature Reviews Rheumatology|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/26553602|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13117|