Psoriasis: not just a skin problem

My first job was at a small business owned by a couple, the wife a geologist and the husband an architect. Both needed to send copies of drawings (for bagel shops and oil fields, usually) to clients on a daily basis, so I spent a few hours a day after high school making those prints and taking out the trash. I learned a lot at that little job, including lessons on social class and, believe it or not, psoriasis.

The architect, you see, had psoriasis, and he would take regular vacations to go to a spa where he would, as I remember it, soak in coal tar baths and other substances that apparently brought him great relief. This sounded absurdly luxurious to me, as my mother wore bangs to cover her psoriasis and wasn’t in the financial position to spend even a day at a spa. Still, the architect was a nice enough fellow and recommended to my mom a homemade formulation of coal tar and ointment that ended up being helpful.

This was the mid-1990s, and I’m not sure if my mother was aware then that systemic therapies were available or if we could afford them. Glucocorticoids and disease-modifying anti-rheumatic drugs, such as prednisone and methotrexate, respectively, have been used for many decades to reduce symptoms.

But these days, you can’t not know that there are more effective therapies for the chronic inflammatory disease than home remedies. Just about every other commercial on television is for a psoriasis drug, most of them biologics. Though estimates vary, we’re talking about a market worth about $11 billion, and that number is growing each year.

Still, the availability of these blockbuster drugs is no comfort to those who cannot access or afford them. A biologic can cost tens of thousands of dollars a year, after all.

In 2016, the World Health Organization issued a global report on psoriasis. The WHO member states had ordered the investigation because “too many people in the world suffer needlessly from psoriasis due to incorrect or delayed diagnosis, inadequate treatment options and insufficient access to care.”

Survey data reported by WHO indicated that the average American patient pays $2,528 every year in out-of-pocket psoriasis care, 34% of which is spent on prescription and over-the-counter drugs. 

Psoriasis comes in several forms, ranging in prevalence, and has several comorbidities, including inflammatory bowel disease, arthritis, depression, cardiovascular disease and metabolic disease. Even if the most noticeable manifestation of the condition is scaly skin, that’s a sign of systemic inflammation that shouldn’t go unchecked.

Below is a collection of recent papers published in ASBMB journals about psoriasis specifically and about chronic inflammation and autoimmunity more broadly. Many thanks to science writers Jonathan Griffin and Laurel Oldach for their skillful curation.

A close-up of a high risk factor for psoriasis

More than 60% of psoriasis patients carry a specific allele of the immune receptor HLA-C known as HLA-C*06:02. Peptides presented to the immune system by HLA-C*06:02 may erroneously trigger autoimmune reactions, but the identity of these peptides—potential targets of new therapies—remain a mystery. In a study in the Journal of Biological Chemistry, researchers in Australia and the U.K. visualized the structure of HLA-C*06:02 bound to several peptides. Their findings provide a basis for how HLA-C*06:02 selects peptides, which is useful information for the identification of psoriasis-related peptides presented by this receptor.

A mutation linked to psoriasis

One genetic mutation linked to psoriasis affects the protein lipin 2. A recent review article in the Journal of Lipid Research by researchers from the University of California, Los Angeles, explains what we know about lipin, which works by removing a phosphate group from a lipid called phosphatidic acid to make a signaling molecule, and how its activity contributes to inflammation and lipoprotein assembly.

How physical trauma triggers psoriasis

Through a process called the Koebner phenomenon, physical trauma can induce the formation of psoriasis plaques. The expression of the receptor ACKR2, which regulates inflammation in psoriasis, is reduced after trauma, but it has not been clear why. Through computer simulations and skin cell experiments, researchers in the U.K. found that cell stress increases expression of a certain microRNAs — short, noncoding RNA molecules — that turn down the dial on ACKR2 expression. The results of the study are published in the Journal of Biological Chemistry.

Sampling skin to find inflammatory lipids

Eicosanoid lipids are one class of molecules involved in inflammation. Some eicosanoids promote inflammation, while others help resolve it. Because eicosanoids act over short ranges within tissues, to fully understand how they contribute to psoriasis, you need to measure them in the skin, where inflammation occurs. In a paper in the Journal of Lipid Research, researchers from the Institute for Biomedicine and Health Sciences in Graz, Austria, along with scientists from the pharmaceutical company Sanofi, established a means for sampling eicosanoids in tiny volumes of fluid in the skin of rats with skin inflammation. The technique could help researchers working on new treatments determine whether drug candidates reach the skin and how they affect inflammation there. 

Identifying new culprits in the psoriasis case

At present, there is no cure for psoriasis. And although many treatments are effective in managing symptoms, they can trigger adverse side effects. To find new therapeutic targets and improve clinical outcomes, researchers at the University of Michigan performed a proteomics screening of psoriasis skin samples from mice and validated their results against human skin. The study, published in the journal Molecular & Cellular Proteomics, revealed the identities of several proteins that were regulated differently in psoriasis and could represent new targets for the disease.

How are psoriasis and cholesterol linked?

Psoriasis is more than skin deep: people who have the disease are also at greater risk of heart attack and stroke. In a 2012 paper in the Journal of Lipid Research, researchers in Austria took a look at HDL, commonly called “good cholesterol,” which was known to be lower in patients with psoriasis. They found that the disease also affects HDL composition and potency, reducing its ability to remove cholesterol from the arteries. The deficiency was stronger in people with more severe psoriasis. The finding suggests has helped researchers understand why psoriasis and cardiovascular disease are linked.

Researchers brandish new weapon against autoimmunity

Signaling pathways initiated by the protein complex NF-κB are characteristic of inflammatory and autoimmune diseases, and it has been shown that this complex is activated whenever the proteins TRAF6 and Ubc13 interact. To devise a way to prevent NF-κB activation, researchers in Germany screened compounds that could potentially prevent TRAF6 and Ubc13 from coming together. They report in the Journal of Biological Chemistry that the small molecule C25-140 inhibited the pro-inflammatory protein interaction and also improved symptoms of psoriasis in mice.