Preliminary findings by Case Western researchers point to kallikrein-related peptidase 6 as possible culprit in the development of psoriatic arthritis.
The discovery of a key protein could change the way psoriasis and psoriatic arthritis is treated in the future.
Researchers at Case Western Reserve University School of Medicine in Cleveland, Ohio — along with several other U.S. universities — found that an overabundance of a protein known as kallikrein-related peptidase 6 (KLK6) can produce and worsen the skin inflammation characteristic of psoriasis.
In addition, KLK6 may — it is important to note that this is early, preliminary research — play a key role in determining which patients will go on to develop psoriatic arthritis, according to the article published earlier this year in The Journal of Clinical Investigation.
About a third of people diagnosed with psoriasis also develop psoriatic arthritis (PsA), but reasons are not understood, the authors wrote.
Future research on KLK6 could be “paradigm-shifting” and would lead to a more personalized method for identifying which psoriasis patients will go on to develop PsA,” so we can modify their treatment accordingly," said Nicole Ward, the study's principal investigator and a professor of nutrition and dermatology at Case Western, in a university news release.
Researchers into many different kinds of disease are researching KLK6, and it may also play a role in the development of cancer, multiple sclerosis, Parkinson’s, and Alzheimer’s disease.
Ward and team sought to understand how the cellular and molecular mechanisms of KLK6 and another protein, protease-activated receptors (PAR)1, promote skin inflammation.
PAR1 is a receptor protein that receives chemical signals from outside a cell, such as from KLK6. “When such signals activate the receptor, they cause cellular/tissue responses, including inflammation,” said the press release.
In their previous research, Ward and colleagues found the skin of psoriasis patients contained as much as six times more KLK6 than normal. They also found that the PAR1 receptor was overproduced in skin and immune cells. Based on that, they theorized that KLK6 might drive inflammation by signaling through PAR1.
When they “turned down” the levels of KLK6 in mouse models, arthritis-like symptoms improved. They also found that "knocking out” PAR1 led to a reduction in skin inflammation and a significant improvement in bone and joint problems.
"To discover that turning down KLK6 eliminated the skin inflammation and even improved the arthritis-like changes — that was unbelievable,” Ward said. ”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.”
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 PsA.