Psoriasis: Researchers explore genetic changes linked to skin lesions

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A new study has found that the genetic changes associated with psoriasis skin lesions also appear in healthy skin elsewhere on the body. Maria Korneeva/Getty Images
  • Psoriasis is an uncomfortable inflammatory skin condition that can lead to other health conditions, most commonly psoriatic arthritis.
  • A recent study used a new investigative method known as spatial transcriptomics to study the causes of psoriasis and how the condition spreads.
  • Researchers have found that the genetic changes associated with psoriasis skin lesions also appear in healthy skin elsewhere on the body, far away from the visibly affected site.
  • The findings suggest specific molecular mechanisms by which psoriasis may lead to other diseases, such as heart disease and diabetes.

More than 7.5 million adults in the United States have psoriasis, according to the National Psoriasis Foundation.

Psoriasis is an autoimmune disease typically characterized by inflammation of the elbows, knees or scalp.

These inflamed, itchy areas or plaques are thick regions of skin tissue covered with scales. Psoriasis is also associated with a number of other health problems.

There is currently no cure for psoriasis; it can flare up unexpectedly and cause discomfort.

Treatment for psoriasis can include medications, injections, topical ointments, or dietary changes, but for many people, the skin condition can persist, which could become frustrating.

In some cases, psoriasis can also lead to other health problems.

While psoriasis is recognized as a malfunction of the immune system, there is still much that is not known about the condition.

Recently, researchers have used a new technique known as spatial transcriptomics to learn more about psoriasis at the molecular level: how it behaves and how it could be linked to the development of other diseases.

The researchers used tissue-scale mapping, or cartography, of psoriasis samples, which revealed increased gene activity in dozens of molecular pathways linked to the development of chronic conditions such as diabetes and cardiovascular disease.

The study results were published June 2 in the journal Science.

Senior investigator Shruti Naik, Ph.D., assistant professor of pathology, medicine and dermatology at NYU Langone Health, said Medical News Today:

Although the plaques are visible on the skin, psoriasis is deeper than the skin. We currently have powerful treatments that control skin symptoms, but we don’t know very well how the disease evolves [the] skin to other areas of the body.

For the study, the researchers sought to develop objective diagnostic measures that could accurately predict severe psoriasis and identify people most likely to develop related disorders.

They analyzed five 4-millimeter fist biopsies from the hip, forearm or buttocks of three healthy control participants, comparing them to 14 samples from 11 people with moderate to severe psoriasis skin lesions.

Nine of the participants with psoriasis also contributed a biopsy from an apparently healthy, uninjured site.

The researchers arranged tissue samples on barcoded arrays with their locations.

They imaged the samples at a tiny 50-micron resolution to assess gene expression based on the cell type observed and its location.

The researchers also accessed and included publicly available srcRNA datasets in their analysis to extract even finer details from their samples.

The study is unique in its use of spatial transcriptomics as a means of studying the molecular behavior of psoriasis.

Spatial transcriptomics captures the locations of affected cells and suggests clues about how they interact.

Transcriptomics is the cataloging of ribonucleic acid (RNA) in a cell. This technique has greatly expanded our understanding of molecular activity in the body.

Transcriptomics has also allowed for the construction of an ever more complete atlas of human cells. However, this atlas lacks information about the tissue context in which they operate, making it difficult to infer the interactions between cells.

The researchers speculated that mapping the locations of cells in their microniches, including how they differ in injured skin, uninjured skin and healthy skin, could reveal previously unseen clues about their behavior.

Spatial transcriptomics then maps the locations of cells within the microniches.

According to the study authors, up to 1 in 3 people with psoriasis develop psoriatic arthritis, a painful joint condition.

Of even greater concern are the various systemic diseases it has been linked with, such as type 2 diabetes, heart disease, and inflammatory bowel disease (IBD).

Dr. Lawrence Green, a fellow at the American Academy of Dermatology and clinical professor of dermatology at George Washington University School of Medicine, noted MNT extension that psoriasis is known to have a similar gene pool to type 2 diabetes.

Among the surprising findings of the studies was increased gene activity in dozens of molecular pathways associated with the control of metabolism and lipid levels, which are associated with the development of diabetes and cardiovascular disease.

Our molecular cartography unexpectedly revealed that even healthy-looking skin areas away from the plaques have profound changes in their cellular and molecular composition, explained Dr. Naik.

We are now investigating whether and how these invisible changes may worsen skin disease or contribute to other systemic comorbidities, said Dr. Naik.

The spatial transcriptomics method showed that psoriasis-related gene activity was also present in skin sites distant from the lesions.

This new insight may help explain how psoriasis systematically affects various areas of the body.

This gives us unprecedented access to molecular changes in the skin that can be used to better understand psoriasis and develop new interventions, said Dr. Naik.

Our atlas will also be accessible to the scientific and medical community so that others who wish to use it for their investigations can do so with ease, he added.

Dr. Green said he found the study’s insights compelling.

It appears that much of the genetic profiles in psoriatic disease found with spatial transcriptomics by the authors match what is already known about skin and local lymphatic and vascular inflammation in psoriasis, Dr. Green noted.

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