Abstract and Introduction
The first single-gene mutation to be directly implicated in psoriasis presents a potential target for intervention.
Generalized pustular psoriasis (GPP) is an episodic, multisystem, inflammatory disorder characterized by fever, leukocytosis, disseminated pustules, and considerable mortality. To identify the disease's genetic basis, researchers studied nine Tunisian families with an autosomal recessive predisposition to GPP.
The investigators identified an area of homozygosity at chromosome 2q13-14 in all affected individuals. In this area of the genome, which contains many genes governing cytokine function and regulation, they identified a mutation that affects the interleukin (IL)-36–receptor antagonist IL-36Ra, weakening the protein and compromising its function.
IL-36Ra is an endogenous antagonist of the IL-36α, β, and γ inflammatory cytokines that normally activate nuclear factor-κB and mitogen-activated protein kinase pathways. Keratinocytes from affected patients produced more IL-8 in response to diverse immune- activating stimuli, and lesional patient skin had elevated levels of multiple inflammatory cytokines.
Journal Watch © 2011 Massachusetts Medical Society
Cite this: A Psoriasis Gene Emerges - Medscape - Aug 17, 2011.