Researchers identified a protein that can not only worsen skin inflammation but also plays a key role in damaging joints and bones of patients with psoriasis.
Not only can the protein KLK6 produce and worsen skin inflammation characteristics of psoriasis, but the protein can play a key role in damaging joints and bones of people with psoriasis, according to research published in The Journal of Clinical Investigation.
Patients with psoriasis show higher rates of diverse comorbid conditions, such as psoriatic arthritis (PsA), which occurs in one-third of patients with psoriasis and can cause severe, disabling joint disease. However, the reason why so many people with psoriasis develop PsA hasn’t been clear.
Since the damage that occurs as a result of PsA is irreversible, identifying patients with PsA early, before too much damage is done to bones, tendons, and joints, is an important consideration, researchers noted.
A team led by Case Western Reserve University School of Medicine researchers discovered that normalizing KLK6 can eliminate skin inflammation and reduce the arthritis-like damage.
"To discover that turning down KLK6 eliminated the skin inflammation and even improved the arthritis-like changes—that was unbelievable," Nicole Ward, PhD, the study's principal investigator and a professor of nutrition and dermatology at the medical school, said in a statement. "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."
In previous research, Ward found that the skin of patients with psoriasis had 6 times more KLK6 than normal. In addition, the PAR1 receptor protein, which causes cellular/tissue responses like inflammation when activated, is overproduced in these patients’ skin and immune cells. The theory that came from these findings was that KLK6 drove inflammation through signaling of PAR1.
In this new study, the researchers overproduced KLK6 through genetic engineering to develop psoriasis-like skin disease. When PAR1 was deleted, there was a reduction in skin inflammation, as well as an 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,” according to Ward.
Billi AC, Ludwig JE, Fritz Y, et al. KLK6 expression in skin induces PAR1-mediated psoriasiform dermatitis and inflammatory joint disease. J Clin Invest. 2020;130(6):3151-3157. doi:10.1172/JCI133159