Gene mutation finding could lead to pustular psoriasis therapy

Results of a new study suggest that mutations in a gene that helps drive immune response may lead to pustular psoriasis. The finding could lead to a more effective treatment for the condition.

The research team, led by Francesca Capon, Ph.D., of King’s College London, found that some patients with pustular psoriasis have mutations on a specific gene called AP1S3, according to a news release. The researchers also found that AP1S3 helps regulate the production of interferon, a cytokine that can trigger inflammation.

The study, which was published in the May issue of the American Journal of Human Genetics and was funded by the National Psoriasis Foundation (NPF), suggests that AP1S3 mutations could alter the immune response by increasing inflammation.

The NPF grant enabled researchers to use gene sequencing technology to study the DNA of nine patients with pustular psoriasis. After narrowing their focus to AP1S3, the researchers studied the gene in 100 other patients. They found gene mutations in approximately 6 percent of those patients.

“Our study is helping to piece together the mechanisms that lead to the onset of pustular psoriasis,” Dr. Capon tells Dermatology Times. “We know that the disease occurs as the result of abnormal inflammatory responses, but identifying an effective treatment will require us to elucidate which immune mediators are specifically malfunctioning. Our study is an important step in that direction, as it has uncovered a new molecular pathway associated with immune dysfunction and disease onset.”

In an earlier study, the King’s College research team 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). When a person has a mutation on this gene, his or her body produces more IL-1. The team is studying whether IL-1 may play a role in the AP1S3 mutation, as well. If so, these patients may be good candidates for drugs that specifically target this cytokine.

More on pustular psoriasis

Late-onset disease demonstrates different genetic factors

Palmoplantar pustulosis merits greater research attention

Experts discuss recent advances in psoriasis treatment