Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis Publication date: June 2019 Source: Journal of Autoimmunity, Volume 100 Author(s): Maxwell J. Heinrich, Caroline A. Purcell, Andrea J. Pruijssers, Yang Zhao, Charles F. Spurlock, Subramaniam Sriram, Kristen M. Ogden, Terence S. Dermody, Matthew B. Scholz, Philip S. Crooke, John Karijolich, Thomas M. Aune Abstract Various sensors that detect double-stranded RNA, presumably of viral origin, exist in eukaryotic cells and induce IFN-responses. Ongoing IFN-responses have also been documented in a variety of human autoimmune diseases including relapsing-remitting multiple sclerosis (RRMS) but their origins remain obscure. We find increased IFN-responses in leukocytes in relapsing-remitting multiple sclerosis at distinct stages of disease. Moreover, endogenous RNAs isolated from blood cells of these same patients recapitulate this IFN-response if transfected into naïve cells. These endogenous RNAs are double-stranded RNAs, contain Alu and Line elements and are transcribed from leukocyte transcriptional enhancers. Thus, transcribed endogenous retrotransposon elements can co-opt pattern recognition sensors to induce IFN-responses in RRMS.