- Psoriasis is an uncomfortable inflammatory skin condition that can lead to other health problems, 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 disease spreads.
- The researchers found that the genetic changes associated with psoriasis skin lesions also show up in healthy skin elsewhere in the body, away from the visibly affected site.
- The results suggest specific molecular mechanisms by which psoriasis can lead to other diseases, such as heart disease and diabetes.
More than 7.5 million adults in the United States suffer from psoriasis, according to the National Psoriasis Foundation.
Psoriasis is an autoimmune disease usually characterized by inflammation of the elbows, knees or scalp.
These inflamed and itchy areas or patches are thick regions covered with scales of epidermal tissue. Psoriasis is also associated with a range of other health problems.
There is currently no cure for psoriasis; it can burst unexpectedly and cause discomfort.
Psoriasis treatment can include medications, injections, topical ointments, or dietary changes, but for many people the skin condition can persist, which can become frustrating.
In some cases, psoriasis can also lead to other health problems.
Although psoriasis is recognized as a dysfunction of the immune system, there are still many unknowns about this disease.
Recently, researchers used a new technique known as “spatial transcriptomics” to learn more about psoriasis at the molecular level: how it behaves and how it might be linked to the development of other diseases.
The researchers used tissue-scale mapping, or mapping, of psoriasis samples, which revealed increased genetic activity in dozens of molecular pathways linked to the development of chronic diseases like diabetes and cardiovascular disease.
The results of the study were published June 2 in the journal Science.
Principal 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, the psoriasis is more than deep. Currently we have powerful treatments that control the skin symptoms, but we don’t fully understand how the disease progresses from (the) skin to other areas of the body.
For the study, researchers sought to develop objective diagnostic measures that would accurately predict severe psoriasis and identify individuals with a greater likelihood of developing associated disorders.
They analyzed five 4-millimeter punch biopsies from the flank, forearm or buttocks of three healthy control participants, comparing them to 14 samples from 11 people with psoriasis skin lesions. moderate to severe.
Nine of the participants with psoriasis also provided a biopsy from an apparently healthy, uninjured site.
The researchers laid out tissue samples on barcoded charts with their locations.
They imaged samples at a tiny resolution of 50 microns to assess gene expression based on the type of cell observed and its location.
The researchers also consulted and included in their analysis publicly available srcRNA datasets to extract even finer details from their samples.
The study is unique in its use of spatial transcriptomics as a way to study the molecular behavior of psoriasis.
Spatial transcriptomics captures the locations of affected cells and suggests clues to 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 enabled the construction of an increasingly complete atlas of human cells. However, this atlas lacks information about the tissue context in which they operate, which makes interactions between cells difficult to infer.
The researchers had hypothesized that mapping the locations of cells in their “microniches” – including how they differ in damaged skin, undamaged skin and healthy skin – could reveal novel clues about their behavior.
Spatial transcriptomics therefore maps the locations of cells in microniches.
According to the study authors, up to 1 in 3 people with psoriasis develop psoriatic arthritis, a painful joint condition.
Dr Lawrence GreenFellow of the American Academy of Dermatology and Clinical Professor of Dermatology at the George Washington University School of Medicine noted at DTM that “psoriasis is known to have a cluster of genes similar to type 2 diabetes”.
Among the study’s startling findings 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 mapping unexpectedly revealed that even areas of skin away from plaques that appear healthy show profound changes in their cellular and molecular makeup,” Dr. Naik explained.
“We are currently investigating whether and how these ‘invisible’ changes may worsen skin diseases or contribute to other systemic comorbidities,” Dr. Naik said.
The spatial transcriptomics method showed that activity of psoriasis-related genes was also present at skin sites distant from lesions.
This new insight may help explain how psoriasis is consistently implicated in various areas of the body.
“This gives us unprecedented access to molecular changes in skin that can be used to better understand psoriasis and develop new interventions,” said Dr. Naik.
“Our atlas will also be accessible to the medical and research community, so those who wish to use it for their investigations can do so easily,” she added.
Dr Green said he found the study’s ideas compelling.
“It appears that many of the genetic profiles of psoriatic disease found with spatial transcriptomics by the authors match what is already known about skin and local lymphatic and vascular inflammation in psoriasis,” noted Dr Green.