Common Reproductive Disorders May Have Immunological Basis

NEWS Common reproductive disorders may have immunological basis Around the world, about 4 million women tissue and the adhesion of organs, leading to mother and child later in life. Delivering the are affected each year by preeclampsia, a life- pelvic pain and even infertility. baby is the only cure. threatening increase in blood pressure during “A lot of evidence in scientific literature Nearly a decade ago, German researchers pregnancy, and an estimated 80 million suffer suggests there may be an immune abnormality found that blood from women with from endometriosis, a disorder involving associated with endometriosis,” says Ninet preeclampsia contained autoantibodies that the lining of the uterus. Theories abound to Sinaii, an epidemiologist at the US National activate the angiotensin AT1 receptor, which explain the onset and progression of these Institute of Child Health and Human releases a chemical that causes blood vessels reproductive disorders, but one idea gaining Development in Bethesda, Maryland. “So it to narrow, driving up blood pressure (J. Clin. traction is that these conditions are actually may be that endometriosis needs to be treated Invest. 103, 945–952; 1999). autoimmune diseases. If this proves true, it as an immune disorder, and that by treating This summer, researchers at the University could lead to earlier diagnoses and much the immune abnormalities we’ll be able to treat of Texas–Houston Medical School reported needed treatments. the disease.” the first lab animal–based evidence that In autoimmune disorders such as lupus Women with endometriosis often suffer from preeclampsia may be a pregnancy-induced and rheumatoid arthritis, the immune well characterized autoimmune diseases. In a autoimmune disease. They injected pregnant system produces ‘autoantibodies’—renegade survey of nearly 3,700 women diagnosed with mice with the angiotensin receptor–activating molecules that attack and destroy healthy the condition, Sinaii and her colleagues found autoantibody, taken from preeclamptic women. tissue. Some researchers believe preeclampsia that 20% had more than one other chronic This induced several features of preeclampsia, and endometriosis may fall into this category disease, and these subjects had higher than including high blood pressure, proteinuria and of diseases because women suffering from expected rates of autoimmune inflammatory placental abnormalities. The group also found http://www.nature.com/naturemedicine the disorders have been shown to have diseases such as Sjögren’s syndrome, a disorder they could prevent these effects by injecting autoantibodies capable of driving up blood in which the body attacks its own tear and mice with a seven–amino acid peptide that pressure and attacking the endometrium, saliva glands (Hum. Reprod. 17, 2715–2724; binds and neutralizes the antibodies (Nat. Med. respectively. 2002). In June, Indian researchers added to 14, 855–862; 2008). In endometriosis, the tissue that normally the growing number of studies conducted “I think the idea that the disease might have lines the uterus grows elsewhere and thickens, over the last two decades that have discovered an immunological basis is a little bit sounder breaks down and bleeds as it would during increased production of autoantibodies against after this paper,” says Ananth Karumanchi, the menstrual cycle. This trapped blood can endometrial cells in women with endometriosis a kidney specialist at Beth Israel Deaconess irritate tissue and eventually cause cysts, scar (Reprod. Biomed. Online 16, 817–824; 2008). Medical Center in Boston, who was not Although Sinaii finds the evidence involved with the study. “It suggests to the field, compelling, she says there are still many to the skeptics like myself, that these antibodies Nature Publishing Group Group Nature Publishing 8 unanswered questions. “Is it because of are not epiphenomenon, that they’re actually immune abnormalities you get endometriosis? involved in the pathogenesis of the disease.” The 200 Or is it that endometriosis is the cause? There next steps, says Karumanchi, will be figuring © are so many factors we can’t say yet what out what triggers autoantibody production and comes first.” A better understanding of the whether they’re involved in subtypes or all of immunological role could eventually lead to the disease. treatments, and measuring antiendometrial Yang Xia, who led the study, says that, if antibodies might provide a new diagnostic confirmed in human trials, the findings could tool (diagnosis can currently take a decade or one day lead to treatments. longer). Because endometriosis is considered Existing antihypertension drugs such as an estrogen-dependent disease, it’s usually losartan block the angiotensin receptor but treated with hormones and anti-inflammatory aren’t an option for pregnant women, because drugs to treat symptoms of pain. “Whether they cause birth defects. And many immune immunosuppressive therapy is more suppressants are similarly dangerous. It may, appropriate for endometriosis is an ongoing however, be possible to block the AT1 receptor question and subject to much more research,” with peptides, as Xia’s team did in the animal Sinaii says. model. “But first we’ll have to make sure this peptide can be stable in the blood circulation,” Searching for answers she says. “Fifteen percent of premature babies The picture may be clearer when considering are due to preeclampsia,” says Xia. “Maybe preeclampsia, a leading cause of maternal targeting this autoantibody can prolong and fetal morbidity and mortality globally, pregnancy.” according to the World Health Organization. How AT1 receptor signaling affects This condition, which affects about 5% preeclampsia remains unclear, but some experts of pregnancies, typically occurs in the last have already begun to speculate that the same trimester and is characterized by high blood receptor might have a role in endometriosis by Dr. Najeeb Layyous / Photo Researchers, Inc Researchers, Photo / Layyous Najeeb Dr. pressure, excess protein in the urine and edema. being expressed in the uterine lining. An unwanted development: Endometriosis It also increases the risk of kidney disease in the Alisa Opar, New York 1172 VOLUME 14 | NUMBER 11 | NOVMEBER 2008 NATURE MEDICINE.

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