New Research Uncovers Why Many With Lupus Are Resistant to Traditional Treatments
Findings Could Lead to Lower Doses of Medication for Lupus Patients, Reducing Serious Side Effects
DALLAS, July 12 /PRNewswire-USNewswire/ -- Two immune system
proteins could be the culprit behind many lupus patients'
resistance to widely used steroid treatments, scientists with the
Baylor Research Institute (BRI) in Dallas announced today. It is
estimated that more than 5 million people suffer from lupus
Currently, those with lupus and other autoimmune diseases,
commonly treat the condition with corticosteroids to suppress their
overactive immune system and prevent it from attacking healthy
tissues which can result in symptoms such as inflammation, pain and
These steroid treatments work by killing certain immune system
cells, including plasmacytoid dendritic cells (PDCs) that
overproduce type 1 interferons, an immune system substance that
contributes to lupus and other autoimmune diseases. However, unlike
other conditions, steroid treatments are not as effective against
these cells in those with lupus.
By largely studying children with systemic lupus erythematosus
(SLE), BRI scientists in collaboration with scientists at Dynavax
in Berkeley, CA, were able to solve the mystery behind the
resistance. They determined that two immune system proteins known
as toll-receptor 7 (TLR7) and toll-receptor 9 (TLR9), cause an
activation of PDCs--the very cells steroids target--negating the
effects of treatment. BRI scientists reported their findings in the
June issue of the journal Nature.
"We have long known that these receptors played a critical role
in lupus, but until now, we didn't know they were directly
interfering with the effects of steroid treatments," says Virginia
Pascual, M.D., one of the principal investigators of the study and
a researcher at Baylor Institute for Immunology Research, a
component of BRI. "By blocking TLR7 and TLR9 function, we may have
found a safer way to treat this debilitating disease."
Currently, large doses of corticosteroids are required to treat
lupus, but can cause serious damage to the organs and create other
side effects such as weight gain, cataracts, hypertension, brittle
bones and thin skin. In children, corticosteroids can also cause
stunted growth. In addition, patients must take other strong
immunosuppressants which can leave them vulnerable to
"The ultimate goal is to reduce the amount of steroids these
patients take because they carry a risk of serious side effects.
Our work suggests that if we can somehow block these proteins from
carrying out their mission, steroid treatments will be more
effective and we may be able to significantly lower the doses,"
explains Dr. Pascual.
While Dr. Pascual's research focused mainly on children, she
says there is no reason to believe these findings would not be true
for adults with lupus as well.
"There are limited treatment options for this disease and the
ones that do exist are very hard on the body. It is a complicated
condition that is difficult to treat so there is an urgent need for
this type of research," says Michael Ramsay, M.D., president of
BRI. "Not only have Dr. Pascual and her team made a huge
contribution to medical research, but they have given hope to the
millions of people who suffer from lupus."
Dr. Ramsay adds that blocking agents for TLR7 and TLR9 are
already in development and could be ready for clinical studies
Funding for this study was provided by the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of
the Department of Health and Human Services' National Institutes of
Health (NIH); the Alliance for Lupus Research, the Mary Kirkland
Center for Lupus Research and a Small Business Innovation Research
Systemic lupus erythematosus (SLE) is an autoimmune disease
which occurs when the body's immune system begins attacking healthy
tissues. As a result, those with the disease often experience
inflammation which causes swelling, pain and tissue damage
throughout the body and in severe cases, serious organ damage. The
exact cause is unknown, but it is thought to be largely genetic.
Lupus primarily affects young women with a peak occurrence between
the ages of 15-40. According to the Lupus Foundation of America,
more than five million people suffer from lupus worldwide.
About Dynavax Technologies
Dynavax Technologies Corporation, a clinical-stage
biopharmaceutical company, discovers and develops novel products to
prevent and treat infectious diseases. For more information, visit
About Baylor Research Institute
Baylor Research Institute (BRI) is a leading research center
focused on bringing clinical research findings from the laboratory
and making them accessible to patient populations of all types.
This concept of "bench-to-bedside" makes the patient the top
priority as BRI works to understand the origin of a disease,
identify potential treatments or preventative therapies and enroll
patients in research trials. With more than 900 active research
projects by 300 investigators in 20 medical specialties, the
institute is nationally and internationally recognized for
developing therapies that advance the care and well-being of our
community through basic science, translational research, continuity
across therapeutic areas and clinical trials.
As part of Dallas-based Baylor Health Care System, and supported
by leading clinicians and world-class scientists, BRI specializes
in several key areas including: immunology and its clinical
indications (such as cancer), auto-immune diseases, rheumatology,
and dermatology as well as transplantation, metabolic diseases,
cardiovascular disease, infectious diseases and oncology. Research
in these areas is bringing the latest discoveries from the
laboratory to patient populations across the country and around the
For more information about Baylor Research Institute, please
Source: Baylor Research Institute
CONTACT: Ashley Howland of Baylor Health Care System,
Posted: July 2010