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Somatic mutations in skin cells do not cause psoriasis, study finds

A psoriasis rash on a leg
Psoriasis can produce dry, itchy skin rashes. Jelena Markovic/Stocksy
  • Scientists are still unraveling the underlying mechanisms involved in psoriasis.
  • Somatic mutations play a role in the development of cancer.
  • A group of researchers recently investigated their role in psoriasis.
  • They concluded that psoriasis is not caused by somatic mutations in skin cells.

Psoriasis is one of the most common skin conditions in the United States. Mediated by the immune system, it causes red, itchy plaques to form on the skin.

It is estimated to affect more than 7 million Trusted Source JAMA Peer reviewed journal Go to source adults in the United States — that’s around 3% of the adult population.

Despite this prevalence and its significant impact on quality of life, many mysteries still surround the condition.

This is partly due to significant gaps in our knowledge regarding the cellular mechanisms that underpin it. 

On the hunt for answers, researchers in a recent study Trusted Source International Journal of Obesity Peer reviewed journal Go to source in the journal Nature Genetics, investigated the potential role of somatic mutations in the genesis of psoriatic plaques.

What are somatic mutations?

Somatic mutations Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source are alterations in DNA that happen after conception. They can occur in any cell type except sperm and egg. 

These types of mutations, which are a normal part of aging, are due to errors during DNA repair, environmental factors, or stress.

Once a somatic mutation occurs, the cell continues to grow and divide as normal, creating a lineage of mutated cells. Sometimes, these mutations provide a competitive advantage. These so-called driver mutations help the cells colonize tissue, replacing healthy cells over time.

As these cells grow in number, they have the potential to influence disease risk and progression as well as how an individual responds to treatment.

Because mutations in oncogenes or DNA repair mechanisms can help cancer cells proliferate, cancer researchers have studied these mutations in detail.

What other diseases can somatic mutations cause?

In more recent years, thanks to the advent of new technology, scientists have started investigating somatic mutations in non-cancerous cells, including cells from the esophagus Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source , colon Trusted Source International Journal of Obesity Peer reviewed journal Go to source , and blood Trusted Source International Journal of Obesity Peer reviewed journal Go to source .

Some believe that somatic mutations might play a role in the pathogenesis of diseases other than cancer. Scientists are focusing on how environmental changes might drive these mutations.

For instance, studies show that treatment with azathioprine — a common drug to treat immune-related conditions — produces mutational signatures in skin Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source and colon Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source cells.

The authors of this recent study also note that somatic mutations may play a causal role in inflammatory bowel disease Trusted Source International Journal of Obesity Peer reviewed journal Go to source (IBD) and chronic liver disease Trusted Source International Journal of Obesity Peer reviewed journal Go to source as well. 

Now, a research group led by scientists from the Wellcome Sanger Institute in England turned their attention to the potential influence of somatic mutations in psoriasis.

Somatic mutations in skin cells and psoriasis risk

To investigate whether somatic mutations might be important, the researchers recruited 111 participants with psoriasis with ages from 18 to 88.

From these people, they took 1,182 punch biopsies. Next, they compared whole genome sequences of cells in psoriatic lesions with cells from nearby patches of healthy skin.

The most common mutations they identified were related to ultraviolet (UV) exposure. These were present even in participants who had not received phototherapy — a common intervention for people with psoriasis.

The second most common mutation was related to the use of psoralens, a drug that helps skin become more light sensitive before UV-A treatment. However, they also identified these mutations in people who had not used psoralens.

The study authors suggest that this might be because, prior to 1996, manufacturers added psorlanens to some sunscreens. Mutations caused by these creams may have persisted since then. 

They said they found no other mutations related to other treatments, such as topical steroids. Similarly, they found no evidence that somatic mutations cause psoriasis.

They also reported that psoriasis doesn’t interfere with the way in which skin cells develop from stem cells.

What next’s in psoriasis research?

While the scientists did not uncover any links between somatic mutations in skin cells and psoriasis, they say their study still adds value.

“Psoriasis is a condition that affects millions of people around the world, impacting their quality of life, and very little is known about why it happens and how we can treat it,” explained Carl Anderson, PhD, a senior group leader at the Wellcome Sanger Institute and a senior study author, in a statement

“While our research did not find a gene where somatic mutations increase susceptibility to psoriasis,” Anderson said, “we were able to quantify the mutational consequences of psoralens exposure on the skin, defining a mutational signature that may help future research.”

The authors also note that while somatic mutations in skin do not appear to play a significant role in psoriasis, they are not entirely off the hook.

Because psoriasis is immune-mediated, there is a chance that somatic mutations in immune cells may be important. This, the authors explain, “is an important direction of future work.”

The problem with psoriasis

Psoriasis still holds many mysteries.

Medical News Today spoke with Dr. Joel Gelfand, a professor of dermatology and epidemiology at the University of Pennsylvania Perelman School of Medicine who was not involved in the study.

We asked why the condition is so difficult to study and how scientists need to approach the problem. “Psoriasis is a lifelong disease that persists for decades, yet clinical trials are short term, typically in weeks or months,” Gelfand explained. 

“To further advance the science and clinical management of psoriasis, the next generation of trials will need to have a pragmatic, randomized design, active comparators, larger sample sizes, and longer durations,” he added.

Medical News Today also contacted Axel Svedbom, PhD, a researcher at the Karolinska Institutet in Sweden who was not involved in the study to ask about the challenges of psoriasis research.

Among other reasons, he said, “The disease appears to be multifactorial and it is possible that risk factors — for example, genetic and environmental — act synergistically. Therefore, you may need more advanced analytical techniques to uncover these relationships.”

So, while somatic mutations in skin cells do not seem to play a major part in psoriasis, using innovative techniques and testing new approaches is vital to help us design better treatments for this common condition.

This article originally appeared on Medical News Today.

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