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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.
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