Up to 60% of patients with autoimmune disease have some degree of sensitivity to ultraviolet light. Sensitivity to sunlight in patients with systemic lupus erythematosus forces them to constantly use a protective cream with a high SPF or hide at dusk.
Failure to take protective measures results in skin inflammation or an outbreak of a wide range of lupus symptoms such as joint pain and fatigue. Read more about the cause of photosensitivity in patients with lupus at estet-portal.com.
The role of interferons in the progression of systemic lupus erythematosus
J. Michelle Kahlenberg, MD, assistant professor of internal medicine at the Michigan Department of Rheumatology, and her multidisciplinary team of researchers are trying to unravel the link between proteins called interferons and systemic lupus erythematosus.
Interferons are released by cells in response to invading pathogens such as viruses, bacteria, and others. The function of interferons is to transmit information to other cells and launch a cascade of protective reactions.
Kalenberg set out to find out which interferons play a major role in the development of photosensitivity in patients with systemic lupus erythematosus.
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Photosensitivity in lupus is due to overproduction of IFN-κ
Researchers compared skin cells from patients with systemic lupus erythematosus and healthy individuals. It was found that epidermal skin cells called keratinocytes (keratin-producing cells), which make up the topmost layer of the skin, showed a significant increase in interferon kappa (IFN-κ) in patients with lupus compared to the control group.
Systemic lupus erythematosus: why timely therapy is important
With the help of genetic engineering, using CRISPR / Cas9 technology, which functions as a pair of genetic scissors, keratinocytes without IFN-κ were created to remove the gene encoding interferon.
The use of CRISPR-Cas techniques for directed genome editing is a promising direction in modern genetic engineering for the treatment of hereditary diseases.
"We have found that photosensitivity in basal keratinocytes disappears after the removal of the IFNK gene using CRISPR/Cas9, which is accompanied by a decrease in inflammation and apoptosis," says Sharkar, Ph.D., researcher in the department of dermatology.
Conversely, cells overexpressing IFN-κ died when exposed to ultraviolet light.
In some patients with lupus, even the light of a photocopier causes a characteristic red "butterfly" rash.
Probably the main function of IFN-κ in normal healthy skin – fight viral infections, but in lupus this system is out of sync and overactive, it enhances the inflammatory response and cell death.
Practical application of data on the cause of photosensitivity
Research is therapeutically promising because drugs for the treatment of rheumatoid arthritis that can block interferons have recently been approved by the FDA.
Oral JAK1/JAK2 kinase inhibitor Baricitinib – it is the first drug in its class to have been shown to be effective in treating lupus.
According to the data presented, baricitinib (4 mg) for 24 weeks reduced the severity of arthritis and rash – common symptoms of lupus. Improvement was noted in 67% of patients. At the same time, baricitinib at a lower dose (2 mg) did not demonstrate efficacy.
Lupus erythematosus: skin manifestations of the disease
The team is currently trying to figure out why IFN-κ increases in the skin of lupus patients and how it triggers apoptosis in keratinocytes. Researchers are also wondering if similar mechanisms exist in other photosensitivity diseases (eg, dermatomyositis).
Active research into the molecular mechanisms of pathological processes helps to create a pathogenetic and promising treatment for patients with systemic lupus erythematosus.
For more information about the pathogenesis of lupus, see the article on our website estet-portal.com in the Dermatology section: Self-destruction mechanism: what happens in systemic lupus erythematosus.
Adapted from Michigan Medicine - University of Michigan
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