Genetics of Psoriasis: Evidence for Epistatic Interaction between Skin Barrier Abnormalities and Immune Deviation
SourceJournal of Investigative Dermatology, 132, (2012), pp. 12
Article / Letter to editor
Display more detailsDisplay less details
Journal of Investigative Dermatology
SubjectN4i 1: Pathogenesis and modulation of inflammation NCMLS 1: Infection and autoimmunity
Psoriasis was until recently regarded as a T-cell-driven disease with presumed (auto)immune mechanisms as its primary cause. This view was supported by clinical data and genetic studies that identified risk factors functioning in adaptive and innate immunity, such as HLA-C*06, ERAP1, the IL-23 pathway, and NF-kappaB signaling. Candidate gene approaches and genome-wide association studies, however, have identified copy number polymorphisms of the beta-defensin cluster and deletion of late cornified envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del) as psoriasis risk factors. As these genes are expressed in epithelial cells and not by the immune system, these findings may cause a change of paradigm for psoriasis, not unlike the reported filaggrin association that has profoundly changed the views on atopic dermatitis. In addition to genetic polymorphisms of the immune system, genetic variations affecting the skin barrier are likely to contribute to psoriasis. Recent studies have shown epistatic interactions involving HLA-C*06, ERAP1, and LCE3C_LCE3B-del, which makes psoriasis a unique model to investigate genetic and biological interactions of associated genes in a complex disease. We present a model for disease initiation and perpetuation, which integrates the available genetic, immunobiological, and clinical data.Journal of Investigative Dermatology advance online publication, 24 May 2012; doi:10.1038/jid.2012.167.
Upload full text
Use your RU credentials (u/z-number and password) tolog in with SURFconextto upload a file for processing by the repository team.