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2015 ; 64
(ä): 66-73
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The immunogenetics of Psoriasis: A comprehensive review
#MMPMID26215033
Harden JL
; Krueger JG
; Bowcock AM
J Autoimmun
2015[Nov]; 64
(ä): 66-73
PMID26215033
show ga
Psoriasis vulgaris is a common, chronic inflammatory skin disease with a complex
etiology involving genetic risk factors and environmental triggers. Here we
describe the many known genetic predispositions of psoriasis with respect to
immune genes and their encoded pathways in psoriasis susceptibility. These genes
span an array of functions that involve antigen presentation (HLA-Cw6, ERAP1,
ERAP2, MICA), the IL-23 axis (IL12Bp40, IL23Ap19, IL23R, JAK2, TYK2), T-cell
development and T-cells polarization (RUNX1, RUNX3, STAT3, TAGAP, IL4, IL13),
innate immunity (CARD14, c-REL, TRAF3IP2, DDX58, IFIH1), and negative regulators
of immune responses (TNIP1, TNFAIP3, NFKBIA, ZC3H12C, IL36RN, SOCS1). The
contribution of some of these gene products to psoriatic disease has also been
revealed in recent years through targeting of key immune components, such as the
Th17/IL-23 axis which has been highly successful in disease treatment. However,
many of the genetic findings involve immune genes with less clear roles in
psoriasis pathogenesis. This is particularly the case for those genes involved in
innate immunity and negative regulation of immune specific pathways. It is
possible that risk alleles of these genes decrease the threshold for the initial
activation of the innate immune response. This could then lead to the onslaught
of the pathogenic adaptive immune response known to be active in psoriatic skin.
However, precisely how these various genes affect immunobiology need to be
determined and some are speculated upon in this review. These novel genetic
findings also open opportunities to explore novel therapeutic targets and
potentially the development of personalized medicine, as well as discover new
biology of human skin disease.