| inflammation

Too Much Protein and Skin Inflammation

The Inflammation, Psoriasis, Joint Pain Connection

Newswise — A team led by Case Western Reserve University School of Medicine researchers has made two major discoveries involving psoriasis, a chronic and debilitating skin disease with no known cure.

The researchers found that an overabundance of a protein known as KLK6 can produce and worsen the skin inflammation characteristic of psoriasis, and—even more significant—that KLK6 can play a key role in damaging the joints and bones of people with the disorder.

The research also revealed that normalizing the level of KLK6 can eliminate skin inflammation and lessen the arthritis-like damage. The research, which used mouse models and patient skin samples, appeared this spring in The Journal of Clinical Investigation.

“To discover that turning down KLK6 eliminated the skin inflammation and even improved the arthritis-like changes—that was unbelievable,” said Nicole Ward, the study’s principal investigator and a professor of nutrition and dermatology at the medical school. “This suggests that clinicians need to aggressively treat patients with psoriasis to prevent the arthritis changes, which generally occur after the skin disease presents itself. Since the joint and bone damage are largely irreversible in patients, prevention becomes critical.”

To address the latest question, genetic engineering was used to overproduce KLK6, which resulted in the development of a psoriasis-like skin disease as well as bone and joint disease. They also found that “knocking out,” or deleting, PAR1 led to a reduction in skin inflammation and, “more profoundly,” Ward said, a significant improvement in bone and joint problems. “These findings suggest that chronic inflammation originating in the skin has the capacity to cause distant joint and bone destruction seen in arthritis.”

Next, the researchers aim to study how skin inflammation causes arthritis-like damage and translate those findings to benefit patients. They also plan to study and compare models that do and don’t develop arthritis to identify biomarkers that can predict the development of psoriatic arthritis.

“If successful, this would be paradigm-shifting and would lead to a more personalized method for identifying which psoriasis patient will go on to develop PsA so we can modify their treatment accordingly,” Ward said.

 

Read the full press release on Newswise.

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