When comparing skin cells (keratinocytes) from patients with healthy skin and patients with lupus, researchers observed that those with the autoimmune condition have an overabundance of a signalling protein called interferon kappa (IFN-κ), according to a study published online ahead of print in the Annals of Rheumatic Diseases (July 18, 2018). Usually triggered by viruses and bacteria, interferons work such as emergency alarms, released by cells in response to invasion.
The investigators hypothesized that higher levels of interferons in lupus patients, particularly in their keratinocytes, explains why up to 60% of lupus patients experience sensitivity to ultraviolet (UV) light or photosensitivity.
“We think that the probable main function of IFN-κ in normal, healthy skin is to fight off viral infections, such as HPV. But in lupus, this whole system is out of sync and overactive,” said study co-author Dr. Johann Gudjonsson, associate professor of dermatology in the University of Michigan in Ann Arbor, Mich. in a press release.
Skin rashes from due to photosensitivity is just one of many
symptoms characteristic of a lupus diagnosis.
Image by OpenStax Microbiology via Wikimedia Commons (www.commons.wikimedia.org/wiki/File:OSC_Microbio_19_02_Lupus.jpg)
Researchers generated keratinocytes without IFN-κ using CRISPR/Cas9 technology to remove the gene encoding the interferon. Then, they compared these skin cells with another set designed to overexpress IFN-κ.
“We found out that all type 1 IFN signalling goes down in basal keratinocytes when you delete, or knock out, the IFN-κ gene using CRISPR/Cas9; we also observed that IFN-κ knockout keratinocytes are unaffected by UV light,” said first author Mrinal Sarkar, PhD, research investigator with the Department of Dermatology at the University of Michigan.
Furthermore, Dr. Sarkar’s team observed that the cells overexpressing IFN-κ died when exposed to UV light. Even without UV light exposure, patients with lupus had higher baseline levels of IFN-κ in their skin. This excess appears to amplify inflammatory response and cell death.
The results generated further lines of inquiry. For example: if similar mechanisms occur in other conditions with photosensitivity, such as dermatomyositis.
The findings are also significant because certain medications recently approved by the U.S. FDA have the ability to block interferons.
Notably, the University of Michigan researchers used the medication baricitinib to block interferon signalling and make lupus keratinocytes appear such as those found in normally-functioning skin. Baricitinib is presently being tested for use in lupus therapy, but not specifically for photosensitivity.
“I am excited to see this go from bench to bedside,” said co-author Dr. J. Michelle Kahlenberg, assistant professor of internal medicine at the University of Michigan. “It may actually happen that some of our work helps to push this forward.”