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NPF-backed research helps ID possible treatment for pustular psoriasis

By Melissa Leavitt

Mutations in a gene that helps drive immune response may lead to pustular psoriasis, according to a new study funded by the National Psoriasis Foundation (NPF).

Researchers found that some patients with pustular psoriasis have mutations on a specific gene, called AP1S3. This finding may help researchers identify better treatments for this difficult-to-treat form of psoriasis.

The study, which appears in the May issue of the American Journal of Human Genetics, proposes that AP1S3 mutations could alter the immune response by increasing inflammation.

"It is not such a stretch of the imagination to think that if you have something wrong with that gene, there will be something wrong with your inflammatory responses" said Francesca Capon, the lead author of the study. Capon was awarded a $50,000 NPF Discovery grant in 2012 to pursue this work.

Support from the NPF enabled researchers to use gene sequencing technology to study the DNA of nine individuals with pustular psoriasis. After narrowing their focus to AP1S3, they studied the gene in 100 other patients, which, Capon noted, is a significant number for such a rare disease. They found gene mutations in approximately 6 percent of patients.

Another gene that carries a risk for pustular psoriasis

AP1S3 is the second gene the research team, based at King's College London, has found that strongly predisposes someone to pustular psoriasis, Capon said.

Previously, they linked mutations on another gene, called IL36RN, to pustular psoriasis. This gene helps regulate inflammation by suppressing inflammatory cytokines such as interleukin-1(IL-1), Capon said. When a person has a mutation on this gene, his or her body produces more IL-1.

Her research team is currently studying whether IL-1 may play a role in the AP1S3 mutation as well. If so, these patients may be good candidates for drugs such as Kineret (anakinra), which specifically target this cytokine.

The team is also working to recruit more patients into their genetic studies, in the hopes of identifying other genes involved in pustular psoriasis. Anyone interested in participating in the study can contact Capon at Francesca.capon@kcl.ac.uk.


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