Researchers Determine a Contributing Genetic Factor of Photosensitivity in Lupus Patients
27 October 2003 - 5:24PM
PR Newswire (US)
Researchers Determine a Contributing Genetic Factor of
Photosensitivity in Lupus Patients Discovery Opens Doors to
Treating Symptom That Can Cause the Body to Attack Itself ORLANDO,
Fla., Oct. 27 /PRNewswire/ -- Researchers at the University of
Pennsylvania School of Medicine have identified a variant of the
human gene for tumor necrosis factor-alpha (TNF-alpha) as the cause
for photosensitivity in lupus patients. This discovery, which was
presented today at the annual scientific meeting of the American
College of Rheumatology, will not only help in treating
photosensitivity, but will also advance research on treating this
potentially damaging symptom and possibly point to one of the
genetic causes of lupus. 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. Editor's Note: You may also find this
news release on-line at http://www.uphs.upenn.edu/news . 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. Penn Health System consists of four hospitals (including
its flagship Hospital of the University of Pennsylvania,
consistently rated one of the nation's "Honor Roll" hospitals by
U.S. News & World Report), a faculty practice plan, a
primary-care provider network, three multispecialty satellite
facilities, and home health care and hospice. 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
http://www.lupusresearchinstitute.org/. DATASOURCE: PENN Medicine
CONTACT: Jen Miller, PENN Medicine, +1-215-349-5657, ; or Lydia
Dorsky, Lupus Research Institute, +1-212-685-4118, Web site:
http://www.lupusresearchinstitute.org/ Web site:
http://www.uphs.upenn.edu/news
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