title: 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.
authors.affiliation: Université Paris Diderot, Service de Rhumatologie, Hôpital Bichat Claude Bernard, APHP, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Dieudé
authors.forename: C
authors.initials: C
authors.lastname: Boileau
authors.forename: Y
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics; D015870:Gene Expression; D058685:Genetic Pleiotropy / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007125:Immunogenetics; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D053278:OX40 Ligand / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C447641:BANK1 protein, human; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D008565:Membrane Proteins; D053278:OX40 Ligand; D050797:STAT4 Transcription Factor; C089251:TNFSF4 protein, human; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22