ScienceDaily (July 29, 2008) — 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. Their research could provide novel diagnostic and
therapeutic possibilities for this intractable disease.
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.
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. It 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.
"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.
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.
Xia's collaborators from the Department of Biochemistry & Molecular Biology at
the UT Medical School at Houston include: Cissy Chenyi Zhou, Ph.D., instructor;
Yujin Zhang, M.D., Ph.D., research associate; Roxanna Irani, graduate student;
Tiejuan Mi; and Rodney Kellems, Ph.D., professor and chairman. Other
collaborators included: Ramin; Hong Zhang, M.D., Ph.D., of the Baylor College of
Medicine; and Edwina Popek, D.O., and M. John Hicks, M.D., Ph.D., D.D.S., of
Texas Children's Hospital.
Research was supported by the National Institutes of Health, the March of Dimes,
the Texas Higher Education Coordinating Board and Merck.
