- Psoriasis is an uncomfortable inflammatory skin condition that may lead to other health conditions, most commonly psoriatic arthritis.
- A recent study used a novel investigative method known as “spatial transcriptomics” to investigate what causes psoriasis and how the condition spreads.
- The researchers found the genetic changes associated with psoriasis skin lesions also appear in healthy skin elsewhere in the body, far removed from the visibly affected site.
- The results 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 scale-covered thick regions of epidermal tissue. Psoriasis is also associated with a range of other health problems.
There is currently no cure for psoriasis; it can flare up unexpectedly and cause discomfort.
Treatment for psoriasis may include medication, injections, topical ointments, or dietary modifications, but for many people, the skin condition may persist, which could become frustrating.
In some cases, psoriasis may also lead to other health problems.
While psoriasis is recognized as a malfunctioning of the immune system, there is still much that is unknown about the condition.
Recently, researchers used a novel technique known as “spatial transcriptomics,” to learn more about psoriasis on a molecular level: how it behaves and how it could be linked to the development of other diseases.
The researchers used tissue-scaled mapping, or cartography, of psoriasis samples, which revealed increased genetic activity in dozens of molecular pathways linked to the development of chronic conditions like diabetes and cardiovascular disease.
The results of the study were published on June 2 in the journal Science.
Senior investigator Shruti Naik, Ph.D., assistant professor in pathology, medicine, and dermatology at NYU Langone Health, told Medical News Today:
“Though plaques are visible to the skin, psoriasis is more than skin deep. Currently, we have powerful treatments that control skin symptoms, but not a very good understanding of how the disease evolves from [the] skin to other areas of the body.”
Investigating psoriasis pathology
For the study, researchers sought to develop objective diagnostic measures that would accurately predict severe psoriasis and identify people with a greater likelihood of developing related disorders.
They analyzed five 4-millimeter punch biopsies from the flank, forearm, or buttocks of three healthy control participants, comparing them with 14 samples from 11 people with moderate to severe psoriasis skin lesions.
Nine of the participants with psoriasis also contributed a biopsy from a seemingly healthy, non-lesioned site.
The researchers arranged tissue samples on arrays barcoded with their locations.
They imaged samples at a tiny 50-micron resolution to assess gene expression by the type of cell observed and its location.
The researchers also accessed and included in their analysis publicly available srcRNA datasets for extracting even finer detail from their samples.
The study is unique in its use of spatial transcriptomics as a means of investigating psoriasis molecular behavior.
Spatial transcriptomics captures the locations of affected cells and suggests clues regarding the way in which they interact.
Transcriptomics is the cataloging of ribonucleic acid (RNA) in a cell. This technique has dramatically expanded our understanding of molecular activity in the body.
Transcriptomics has also allowed the construction of an increasingly comprehensive atlas of human cells. However, this atlas lacks information regarding the tissue context in which they operate, making interactions between cells challenging to deduce.
The researchers had hypothesized that mapping the locations of cells in their “microniches” — including how they differ in lesioned skin, non-lesioned skin, and healthy skin — might reveal previously unseen clues as to their behavior.
Spatial transcriptomics, therefore, maps out the locations of cells within microniches.
How psoriasis may lead to other health conditions
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 with which it has been linked, such as type 2 diabetes, heart disease, and inflammatory bowel disease (IBD).
Dr. Lawrence Green, an American Academy of Dermatology fellow and clinical professor of dermatology at the George Washington University School of Medicine noted to MNT that “psoriasis is known to have a similar gene clustering as type 2 diabetes.”
Among the study’s surprising findings were increased genetic 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 skin areas far away from plaques that look healthy have profound changes in their cellular and molecular makeup,” Dr. Naik explained.
“We are now investigating if and how these ‘invisible’ changes may worsen skin disease or contribute to other systemic co-morbidities,” Dr. Naik said.
Implications for psoriasis treatment
The spatial transcriptomics method showed that psoriasis-related gene activity was also present at skin sites far away from lesions.
This new insight may help explain how psoriasis is systemically involved in various areas of the body.
“This gives us unprecedented access to the molecular changes in the skin that can be used to better understand psoriasis and develop new interventions,” Dr. Naik said.
“Our atlas will also be accessible to the research and medical community, so others who wish to use it for their investigations can do so with ease,” she added.
Dr. Green said he found the study’s insights convincing.
”It seems much of the genetic profiles in psoriatic disease found with spatial transcriptomics by the authors fit what is already known about skin and local lymphatic and vascular inflammation in psoriasis,” Dr. Green noted.
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