A new study reveals hidden features of skin inflammation that “could tell us who is more likely to develop severe psoriasis,” as well as related disorders “such as arthritis and cardiovascular disease.”

Manifesting as thick, inflamed patches of skin adorned with silvery scales, Psoriasis is a disorder where the body’s defense mechanism erroneously targets its own healthy cells. This autoimmune condition instigates hyperactivity within the immune system, resulting in rapid skin cell proliferation. The consequence is an unusually swift skin cell turnover, occurring in days as opposed to the typical weeks, leading to the formation of the telltale scales and patches associated with Psoriasis, as stated by the National Psoriasis Foundation.

This condition doesn’t discriminate by age, often making its first appearance during the second decade of life, with a lesser prevalence during the fifth and sixth decades.

While predominantly a dermatological condition, Psoriasis can significantly impact various aspects of an individual’s health. For instance, psoriatic arthritis, a form of inflammatory arthritis, poses a heightened risk to those afflicted with Psoriasis.

Furthermore, individuals suffering from moderate to severe Psoriasis may also face an increased risk of cardiovascular conditions, including heart attacks and strokes. This increased susceptibility may be attributed to the persistent inflammation caused by Psoriasis that not only affects the skin and joints but potentially extends to the heart and blood vessels as well.

A recent study sheds light on distinguishing mild from severe forms of Psoriasis, focusing on the activity of critical cells and signaling pathways underneath and beyond the visible, red, flaky skin lesions.

Spearheaded by a team at the NYU Grossman School of Medicine, the research provides detailed insights into the hidden characteristics of inflammation and their comparison across varying degrees of psoriatic conditions. The findings could potentially illuminate why localized skin inflammation can trigger systemic effects. The researchers emphasize that around 20% of psoriasis patients eventually experience joint inflammation, or psoriatic arthritis. Their results might also provide potential insights into the links between psoriasis, type 2 diabetes, heart disease, and inflammatory bowel disease.

Published in Science Immunology today, their analysis uncovered that the positioning and prevalence of cell clusters called fibroblasts – crucial inflammation regulators, together with macrophages – a form of white blood cell, differed and increased in the superficial skin layers in acute cases of psoriasis.

Additionally, the scientists identified that, in skin samples from individuals with moderate to severe psoriatic disease, there was heightened gene activity in over thirty-six molecular pathways related to metabolism and lipid level regulation, factors that commonly malfunction in diabetes and cardiovascular diseases. Interestingly, this enhanced gene activity was also observed in clear skin, distant from any lesions.

“Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis,” adds co-senior author Dr. Jose Scher, “as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease.”

“Having found signals with potential systemic consequences,” points out Scher, “we are now working to understand how skin inflammation can lead to widespread disease affecting other organs.”

Co-senior investigator Shruti Naik points out that “Our study serves as a valuable resource for the scientific community, offering the most comprehensive archive of cellular and molecular features involved in both diseased and healthy skin.”

An estimated 8 million individuals in the United States, and a staggering 125 million globally, live with the burden of psoriatic disease, a condition that shows no gender bias.

The recently conducted study, as Scher points out, extends its investigative scope beyond the existing diagnostic methods that predominantly concentrate on the noticeable signs of skin lesions, neglecting the concealed systemic and molecular impacts. Although numerous treatment options such as steroids and immunosuppressive drugs effectively minimize inflammation and symptomatic discomfort, they fall short of targeting the fundamental triggers of the disease.

This novel study employs the innovative technique of spatial transcriptomics, which intricately maps the molecular and cellular interplay within a specific tissue. Researchers scrutinized the intact skin samples from 11 individuals presenting a range of mild to severe psoriatic conditions, and three healthy adults devoid of psoriasis.

They believe spatial transcriptomics offers superior insight compared to other techniques that focus on single cells, as it provides a comprehensive image-based map showcasing the location of cells within tissues and their communication networks.

As the next step, Naik indicates the team’s intention to leverage this recent analysis to unearth the biological processes that instigate skin inflammation in one region and how it influences skin or other organs elsewhere in the body. Additionally, they plan to expand their research to include larger patient cohorts and to analyze lesioned and non-lesioned skin from the same patients. This approach aims to comprehend why the disease naturally resolves in certain cases and why patients exhibit varied responses to identical anti-inflammatory treatments.

In a move to aid the global research community, the study’s co-lead investigator and bioinformatics specialist, Ikjot Sidhu, has made the spatial transcriptomics analysis available at https://zenodo.org/record/7813973 and https://zenodo/org/record/7562864.

Source: 10.1126/sciimmunol.abq7991

Image Credit: Getty