Reflections on Ten Years of History of, and Future Prospects for, GW182 and GW/P Body Research

Abstract

The literature on human autoantibodies in systemic rheumatic diseases has clearly elucidated major autoimmune targets, many of which are nucleic acid-protein macromolecular complexes or subcellular particles (Tan et al. 1988). Well-documented examples of these include the ribonucleoprotein Sm/RNP complex comprised of key components of U-rich small nuclear ribonucleoproteins (UsnRNPs) that are critical for processes in mRNA splicing, and chromatin subunits composed of DNA, histones and high mobility group proteins. Although there are still unanswered questions about why these are the targets of the B-cell response, the current thinking is that these nucleic acid-protein complexes are preferred target autoantigens in systemic autoimmune diseases because of their interactions with toll-like receptors (TLR). TLR3, 7, and 9 are primarily located in the endosomes and are responsible for sensing of endogenous RNA and DNA ligands (Kawai and Akira 2009). Thus, endogenous nucleic acids-protein complexes have a higher tendency to stimulate a B-cell autoimmune response.