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Biochemists
at The University of Texas Medical School at Houston say they are the
first to provide pre-clinical evidence that pregnancy-induced high
blood pressure or pre-eclampsia may be an autoimmune disease.
About Pre-eclampsia
- Pre-eclampsia
typically occurs in the last trimester of pregnancy and is
characterized by a sudden increase in blood pressure, excess protein in
the urine and swelling of the hands, feet and face.
- Pre-eclampsia
affects about
one in 20 pregnancies and the only cure is delivery of the baby.
- Pre-eclampsia contributes to 15 percent of premature babies and is
associated with a high incidence of mother and infant morbidity and
mortality in the United States.
- The risk factors for pre-eclampsia
include: having a history of pre-eclampsia; being obese; having twins,
triplets or other multiples; and developing gestational diabetes.
About Autoimmune Disorders
An autoimmune disease is a condition that occurs when the immune system
mistakenly attacks and destroys healthy body tissue.
Autoimmune disease can affect virtually every site in the body, including the
endocrine system, connective tissue, gastrointestinal tract, heart,
skin, and kidneys.
At least 15 diseases are known to be the direct
result of an autoimmune response, while circumstantial evidence
implicates >80 conditions with autoimmunity. There are more than 80
different types of autoimmune disorders.
The Pre-eclampsia Autoimmune Disease Study
Scientists in the laboratory of Yang Xia, M.D., Ph.D., an assistant
professor of biochemistry and molecular biology at the UT Medical
School at Houston, provided evidence of the connection by inducing
symptoms similar to pre-eclampsia in pregnant mice that had been
administered autoantibodies isolated from women with the condition.
This proof-of-principle experiment is called adoptive transfer.
“There is no effective treatment
for pre-eclampsia other than delivery, in part because of the lack of
complete understanding of the disease,” said Susan Ramin, M.D., study
co-author, the Emma Sue Hightower Professor and Chair in the Department
of Obstetrics, Gynecology and Reproductive Sciences at the UT Medical
School at Houston and a member of the medical staff of Memorial Hermann
- Texas Medical Center. “This collaborative research is important
because of its potential to lead to a possible cure of pre-eclampsia in
pregnant women. Using the animal model we were able to prevent
pre-eclampsia in pregnant mice. I don’t want to overstate the
implications, but this is clearly a very exciting time for all of us
involved in the research. We plan to focus our efforts in expanding
this research to pregnant women.”
Unlike antibodies which attack
foreign substances and clear diseases from the body, autoantibodies
attack their own cells and cause conditions like lupus in which a
person's immune system attacks the body's own organs and tissues, said
Xia, the senior author. In the case of pre-eclampsia, autoantibodies
are believed to bind and activate an angiotensin receptor that results
in artery constriction.
Pre-eclampsia like symptoms were
prevented when the pregnant mice were given agents designed to block
the activation of the angiotensin receptor.
“The antibody
injection model of pre-eclampsia described here provides strong
experimental support for our working hypothesis that pre-eclampsia is
an autoimmune disease in which angiotensin receptor–activating
autoantibodies contribute to many features of the disease,” Xia and her
colleagues wrote in the paper.
If the research is confirmed in
human trials, Xia believes this information could be used for both the
earlier diagnosis and treatment of pre-eclampsia. By measuring
autoantibody levels, clinicians could detect the disease weeks before
symptoms appear. In addition, new drugs could be developed to inhibit
the activation of the angiotensin receptor.
In the meantime, Xia said further research is needed to determine what triggers the production of the autoantibodies.
“Pre-eclampsia
is one of the leading causes of prematurity and Small For Gestational
Age (SGA) infants. Many of these babies are born with underdeveloped
lungs or poor lung clearance of fluid, necessitating neonatal intensive
care admission and various respiratory therapies to support their
breathing. We continue to struggle to find a proven prevention or
treatment solution for these problems," said Nehal A. Parikh, D.O., an
assistant professor of neonatal-perinatal medicine at the UT Medical
School at Houston and a member of the medical staff of Children's
Memorial Hermann Hospital.
“If targeting the angiotensin
receptor autoantibody is a useful strategy to treat pre-eclampsia, then
it will also be a useful way to prevent and treat SGA associated with
pre-eclampsia,” Xia said.
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