Study suggests somatic mutations do not cause, spread psoriasis

Key takeaways:

• There was a minimal difference in the number of mutations in psoriasis patches compared with healthy skin.
• However, a mutational signature was linked to the use of psoralens.

Published data from sequenced skin samples of 111 individuals with psoriasis suggest that the chronic condition is not started or spread by somatic mutations.

Somatic mutations are a known catalyst and spreader for other inflammatory diseases such as inflammatory bowel disease and chronic liver disease; however, according to the study published in Nature Genetics, the same does not apply to psoriasis.

“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,” Carl A. Anderson, PhD, senior group leader at Wellcome Sanger Institute and an investigator of this study, said in a press release from the institute.

In the study, Anderson and his colleagues set out to study the effects of psoriasis on the somatic mutation landscape of the skin. They took skin samples from psoriasis patches and healthy skin of 111 individuals with psoriasis. Using laser capture microdissection to isolate 1,182 samples, the researchers then analyzed the samples by whole genome or exome sequencing.

What they found is that there is only a slight increase in the number of mutations in psoriasis patches compared with healthy skin, with those differences being minimal, according to the press release. Further, the researchers found no functional difference between psoriatic and healthy tissue.

The authors did, however, identify four new driver mutations in both psoriasis and other skin tissue that gave skin cells an advantage over neighboring cells. These mutations were found in the GXYLT1, CHEK2, ZFP36L2 and EEF1A1 genes.

While there may not be a link between psoriasis and a specific somatic mutation, the authors did find a mutational signature linked to the use of psoralens.

Psoralens, a class of linear furanocoumarins, are found in many crops including citrus fruits and figs. Their synthetic forms are used in psoriasis phototherapy treatment, along with ultraviolet-A light (PUVA treatment), and were used in self-tanners and sunscreens until European safety regulations limited their production in 1996.

In the study, 24 of the 111 tested participants showed evidence of the psoralen mutation signature. A higher number of PUVA treatment cycles was associated with an increased mutation burden, with individuals that had more than 200 PUVA cycles experiencing significantly higher psoralen mutation burden than those without history of PUVA treatment (extra exonic mutations per clone, 616; 95% CI, 407-826).

On the other hand, 11 of these 24 participants had no history of PUVA treatment, suggesting that the signature may also be caused by environmental psoralen exposure such as past-usage of psoralen-containing sunscreens and lotions.

“We were able to quantify the mutational consequences of psoralens exposure on the skin, defining a mutational signature that may help future research,” Anderson said in the release. “We also found that the way in which skin cells develop from stem cells is, reassuringly, unaltered by psoriasis.”

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