Shining a light on the drivers of photosensitivity in systemic lupus

Light sensitivity forces many patients with lupus to avoid the sun. Researchers haven’t worked out how ultraviolet light from sunlight or other types of light cause rashes and other problems. Our study will use state-of-the art technology to compare the effects of ultraviolet light on patients with lupus who are sensitive to light, patients with lupus who are not light-sensitive, and people who don’t have the disease. We will measure the changes in skin samples from the three groups to map out differences that are driving skin inflammation. Discovering the changes that occur in skin exposed to ultraviolet light could reveal whether existing drugs will work against the symptoms or provide clues for development of novel therapies.

What this study means to people with lupus

“Many patients with lupus develop skin rashes and other symptoms after exposure to sunlight, but the mechanism for how this happens remains unclear. We plan to analyze skin from patients with lupus to identify the molecular changes that occur after exposure to sunlight. Our findings will identify whether existing drugs might reduce or prevent skin inflammation or help researchers develop new treatments.”

Cutaneous inflammation is a prevalent and often difficult-to-treat manifestation of systemic lupus erythematosus (SLE) that is frequently associated with and may lead to exacerbation of systemic disease. Ultraviolet (UV) light exposures are a frequent trigger for skin inflammation in SLE patients, and yet the mechanisms which drive this photosensitivity are poorly understood. The factors which contribute to the propensity for inflammation in SLE skin are thus obvious and important targets for preventative and therapeutic considerations. Consequentially, it is important to uncover the driving factors of photosensitivity in SLE skin. We have identified chronic, keratinocyte-derived interferon signaling as one contributing factor to photosensitivity, but to thoroughly understand and target this phenomenon, a broad, unbiased approach is required to advance the biology of SLE and to discover specific targets for study. We hypothesize that the differences in SLE skin before and after UVB-driven inflammation will identify important pathogenic mediators of photosensitivity. Thus, we propose to subject healthy control, photosensitive SLE and non-photosensitive SLE patients to small amounts of UVB exposure followed by skin biopsy and the study of their immune and inflammatory responses with a combination of single cell RNA-seq, total RNA-seq, and tissue CyTOF to identify and anatomically map the cell populations and inflammatory pathways activated in photosensitive patients. The data will be analyzed with the following Aims: 1. Compare and contrast control skin with photosensitive and non-photosensitive SLE “normal” skin at baseline. 2. Compare and contrast UVB responses in control vs. photosensitive SLE vs. non-photosensitive SLE skin to identify specific responses that are unique to photosensitive patients. This work will develop novel and highly important data on lupus skin and will generate targets for further study for preventative and therapeutic uses in SLE.