Immunogenetics of systemic sclerosis

Abstract

In the field of genetics of SSc, we are currently reaching a period of rapid data production. Several themes are already rising from the first wave of results. First, some genetic variants clearly predispose to multiple autoimmune diseases, thus providing evidence for a shared autoimmune genetic background. Second, multiple genes are involved in the SSc predisposition and as expected the genetic associations are quite modest. Third, unless for a small number of exceptions, the causative genetic variations have not been definitively identified yet. Lastly, to date, the most convincing associations detected relate to genes playing a pivotal role in both innate and adaptative immunity. Indeed, additionally to the MHC, candidate gene studies have convincingly and reproducibly identified PTPN22, IRF5, STAT4, C8orf13-BLK, BANK1 and TNFSF4 as SSc susceptibility genes. Although these results have substantially advanced our understanding of the SSc pathogenesis, both gene-gene and gene-environment studies are now awaited in order to further improve our understanding of this multifacet disease. Finally, we should keep in mind that SSc is a very severe that is until now unfortunately free of effective therapy. Therefore, the identification of new susceptibility genes may offer a rich source of new hypotheses and experimental directions to follow that we should try to assembly in a near future to generate innovative therapies to fight this dramatic disease.