Victoria Werth, MD Associate Professor of Dermatology and Medicine in Penn's School of Medicine, working in collaboration with Kathleen E. Sullivan, MD, PhD, Associate Professor of Pediatrics, University of Pennsylvania School of Medicine, and attending physician in The Children's Hospital of Philadelphia Division of Allergy and Immunology, identified a variant of the TNF-alpha promoter that showed increased activity when exposed to sunlight. This discovery is crucial to understanding photosensitivity and lupus because TNF-alpha has been shown to stimulate apoptosis, the process of cellular death. As skin cells die, intracellular proteins move to the cell's surfaces where they stimulate an immune reaction. The immune system makes new antibodies against these proteins and triggers further inflammation, causing the body to attack its own internal organs - just from sunlight.
As part of her research, Werth has studied the effects of TNF-alpha in cultured cells and patients. She has found that a large percentage of patients with subacute cutaneous lupus erythematosus (SCLE), a highly photosensitive form of lupus, has one or even two copies of the TNF-alpha variant gene. Thus, when these cells are exposed to sunlight, the gene becomes overactive, and a large quantity of TNF-alpha is produced. This causes nearby skin cells to undergo apoptosis, therefore stimulating the immune system and triggering flares that could affect internal organs.
The increased presence of TNF-alpha in lupus patient cells suggests that additional genetic variants are associated with increased TNF-alpha production in response to sunlight. This could mean major advances in treating lupus patients. "These results now let us think about different categories of drugs for treatment of photosensitivity," says Werth. While drugs like antimalarials and thalidomide are already used to inhibit TNF-alpha and treat the skin manifestations of lupus, these findings allow researchers to test newer drugs that inhibit TNF-alpha. Also, as researchers better understand the wavelengths of light that trigger the disease, they can develop sunscreens that will hopefully improve the ability to block the harmful effects of sunlight.
Funding for this research was provided by the Lupus Research Institute through their Novel Research Program, which seeks to support highly promising novel approaches to discover the cause, improve the treatment and cure lupus.
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PENN Medicine is a $2.2 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation's first integrated academic health system).
Penn's School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
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Founded in 1855 as the nation's first pediatric hospital, The Children's Hospital of Philadelphia is ranked today as the best pediatric hospital in the nation by U.S.News & World Report and Child magazine. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 381-bed hospital recognition as a leading advocate for children and adolescents from before birth through age 19. Children's Hospital operates the largest pediatric healthcare system in the U.S. with more than 40 locations in Pennsylvania, New Jersey and Delaware.
The Lupus Research Institute (LRI) is the national nonprofit organization that supports only the highest-ranked novel research in lupus. With a broad-based research agenda, the LRI seeks to change the course of lupus research to improve treatment, prevent and cure lupus. Created in collaboration with leading lupus scientists, the LRI encourages researchers to search for answers solely in unconventional, innovative ways. The LRI also supports the development of new clinical trial methodologies that will accelerate the testing of promising agents in lupus patients. Currently, the LRI has awarded more than 7 million in grants, supporting 35 scientists at leading medical institutions around the country. Specific information on individual research projects can be obtained at www.lupusresearchinstitute.org.