[HTML][HTML] Genetics of psoriasis: evidence for epistatic interaction between skin barrier abnormalities and immune deviation

JGM Bergboer, PLJM Zeeuwen, J Schalkwijk - Journal of investigative …, 2012 - Elsevier
JGM Bergboer, PLJM Zeeuwen, J Schalkwijk
Journal of investigative dermatology, 2012Elsevier
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-κB signaling. Candidate gene
approaches and genome-wide association studies, however, have identified copy number
polymorphisms of the β-defensin cluster and deletion of late cornified envelope (LCE) 3B …
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-κB signaling. Candidate gene approaches and genome-wide association studies, however, have identified copy number polymorphisms of the β-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.
Elsevier