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Cell activity in psoriasis may predict disease severity and provide clues to comorbidities



The activity and clustering of certain cell types may distinguish mild and severe forms of psoriasis, with severe disease altering the cellular and metabolic composition of distal unaffected skin sites, according to a new analysis using single-cell transcriptomic technology.

On the surface, psoriasis severity is identified based on the visible lesions, Rochelle L. Castillo, MD, of the division of rheumatology and the NYU Psoriatic Arthritis Center, NYU Langone Health, New York, and colleagues wrote in their study, published in Science Immunology. Although cellular and molecular features of inflammatory skin diseases such as psoriasis have been characterized, activity at the tissue level and its systemic impact has not been explored.

“Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis, as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease,” study co–senior investigator Jose Scher, MD, director of the Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity at NYU Langone Health, said in a press release accompanying the publication of the findings. “Having found signals with potential systemic consequences, we are now working to understand how skin inflammation can lead to widespread disease affecting other organs,”

In the study, the researchers used spatial transcriptomics, a technique that positions tissue sections onto genetic arrays to determine gene expression by cell type and histological location, helping to create a broad image-based map of where certain cell types are located in tissues and with what other cells they are communicating. They characterized the cell activity of skin samples from 11 men and women with mild to severe psoriasis/psoriatic arthritis, and three healthy adults who did not have psoriasis. They defined the cellular composition of 25 healthy skin biopsies and matched skin biopsies from psoriatic lesional and nonlesional skin, and identified 17 distinct clusters of cells, which they grouped into epidermal, dermis, pilosebaceous, and adipose categories.

The researchers found that cell activity associated with inflammation, as shown by clusters of fibroblasts and dermal macrophages, was more common in the upper layers of the skin in samples from patients with more severe psoriasis, compared with healthy control samples.

They also examined patterns of immune activity at the cellular level and found significant patterns around the upper follicle, around the perifollicular dermis, and within the hair follicle, where immune cells were enriched in healthy skin. Other cells enriched in these upper layer areas in healthy skin included dendritic cells, innate lymphoid cells, T helper cells, T cytotoxic cells, and myeloid cells.

Clusters of fibroblasts and macrophages, which are associated with inflammation, were clustered in psoriatic lesional skin, which also showed more inflammation at the dermal and suprabasal epidermal levels. B lymphocytes also were more prevalent in lesional skin.

The researchers then analyzed the skin samples according to disease severity; mild psoriasis was defined as a Psoriasis Area and Severity Index score less than 12; moderate to severe disease was defined as a PASI score of 12 or higher. The macrophage, fibroblast, and lymphatic endothelium–associated clusters distinguished mild and moderate to severe endotypes.

The pathology of moderate to severe psoriasis in lesional and nonlesional skin showed the extensive effects of psoriasis-related inflammation. Although nonlesional mild disease was clustered with healthy skin, in cases of moderate to severe disease, nonlesional and lesional groups were clustered together. This effect was segregated according to disease severity, independent of the presence of joint disease, and “was particularly evident in distal, nonlesional samples,” the researchers wrote.

The researchers also found evidence of increased gene activity in more than three dozen molecular pathways associated with metabolism and lipid levels in areas of lesional and nonlesional skin, Dr. Scher said.

The findings were limited by several factors including the small sample size and the limits of spatial transcriptomics technology resolution, the researchers wrote. “As this technology evolves, platforms with higher density, and by extension, resolution, of spatially barcoded beads will provide more granularity about cellular microenvironments in healthy and diseased states.”

The study was supported by the National Institutes of Health, the National Psoriasis Foundation, the NYU Colton Center for Autoimmunity, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the Beatrice Snyder Foundation, The Riley Family Foundation, the Rheumatology Research Foundation, and the NY Stem Cell Foundation. Dr. Castillo had no financial conflicts to disclose. Dr. Scher has served as a consultant for Janssen, Abbvie, Novartis, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb, and has received research funding from Janssen and Pfizer.

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