Findings from a new study show that normal-appearing skin in patients with cutaneous lupus erythematosus contains the same inflammatory signals that are seen when their skin develops a rash—in some cases at even higher levels.
In the study, published in Science Translational Medicine (April 27, 2022; 14(642)), researchers evaluated normal-appearing skin, lesional skin, and circulating immune cells from lupus patients through RNA sequencing. They found that normal-appearing skin of patients with lupus represents a type I interferon–rich, prelesional environment that alters gene transcription in all major skin cell types. Interferon is also known to contribute to sensitivity to ultraviolet (UV) light. This environment strongly distorts predicted cell-cell communication networks.
“This really starts to piece the puzzle together of how inflammation seen in lupus patients may be related to skin exposures such as UV light,” said J. Michelle Kahlenberg, MD, PhD, senior author of the study and rheumatologist at University of Michigan Health, in a press release. “We were able to see the properties of normal-appearing skin in unparalleled resolution, suggesting that the skin is primed for inflammatory reactions.”
Inflammatory changes were seen in both keratinocytes and in fibroblasts. “This is important because we have a new drug that can block interferon signalling in lupus, and people are trying to figure out how best to use that medication,” said Dr. Kahlenberg, who is also an associate professor of rheumatology at U-M Medical School. “So, validating this abnormality in the interferon pathway could be essential for determining the best course of treatment for scores of lupus patients.”
The research team also found that lupus-enriched CD16+ immune monocytes travel from the blood of lupus patients into their skin and in the process gain proinflammatory phenotypes.
Dr. Kahlenberg calls this change “cell education.” The lupus skin environment itself—specifically, the interferon within the skin—appears to change the monocytes in a way that sets up the rest of the immune system to be turned on.
“These interferon-educated immune cells seem to be priming many different cell types in the skin to overreact to stimuli with excessive inflammatory responses, manifesting as disfiguring skin lesions,” said Allison C. Billi, MD, PhD, co-first author of the study, dermatologist at U-M Health and assistant professor of dermatology at U-M Medical School, in the release. “We don’t yet know all of the stimuli that can tip the balance and precipitate these rashes, but UV light certainly appears to be one of them.”