Maternal autoantibodies might trigger autoimmune diabetes

SCIENCE AND MEDICINE

Maternal autoantibodies might trigger autoimmune diabetes producing insulin-specific antibodies, also showed a far reduced propensity for diabetes development. Finally, embryos implanted

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into foster mothers whose serum antibodies did not contain an isletreactive component had a strikingly reduced diabetes incidence. Naji says that his team’s findings suggest that maternal autoantibodies transmitted to offspring could trigger or exacerbate the onset of a T cellmediated autoimmune disease—in this case, type 1 diabetes. For now, however, the precise mechanism underlying the pathogenic role of autoantibodies in diabetes onset remains elusive, although Naji suggests three possibilities: “Autoantibodies may augment the uptake

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ype 1 diabetes has long been defined as a T cell-mediated autoimmune disease, and autoantibodies against pancreatic islet ␤-cell antigens act as markers of disease susceptibility and progression, but are generally thought to have no role in pathogenesis. Now, a new study has found that such autoantibodies might have a pathogenic role after all, and that mothers carrying these antibodies could pass them on to their offspring, triggering type 1 diabetes. In three related experiments, Ali Naji (University of Pennsylvania School of Medicine, Philadelphia, PA, USA) and colleagues used transgenic, non-obese diabetic mice to show that offspring of mothers that transferred anti-islet autoantibodies to them had a higher incidence of diabetes than offspring that did not receive these antibodies (Nat Med 2002; 8: 399–402). In the first experiment, mothers without B lymphocytes, which are required to produce antibodies, gave birth to progeny that had a greatly reduced diabetes incidence. The second test showed that offspring of mothers with B lymphocytes, which were genetically manipulated to be incapable of

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and presentation of islet antigen(s) to pathogenic T lymphocytes; autoantibodies, present early in life, may cause subtle damage to islet ␤ cells, thereby initiating a T cell-driven autoimmune cascade; or autoantibodies may recruit inflammatory cells or mediators to the islet milieu early in diabetes pathogenesis.” In an accompanying commentary, Matthias von Herrath (La Jolla Institute for Allergy and Immunology, San Diego, CA, USA) suggests that the findings “present a strong case for an essential role of maternal antibodies” in the experimental mouse model (Nat Med 2002; 8: 331–33). “They indicate that at least in very early childhood cases of type 1 diabetes, the transfer of pathogenic maternal antibodies likely directed to islet antigens can set off the autoimmune process leading to type 1 diabetes”, von Herrath told The Lancet. However, he adds that it is uncertain whether the same thing happens in human beings, and that further studies differentiating between insulin-therapy induced antibodies and endogenous autoantibodies in mothers will be needed. Angela Pirisi

Implanted device could reduce risk of stroke in atrial fibrillation

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n international team of researchers has successfully completed tests in human beings of a device that could greatly reduce the risk of stroke for some people with atrial fibrillation, according to a study published this week. The team, led by Horst Sievert (Cardiovascular Centre Bethanien, Frankfurt, Germany), inserted the device into the opening of the left atrial appendage (LAA), a small pouch in the heart’s left upper pumping chamber, in which clots can easily form. “In atrial fibrillation blood flow velocity in the left atrial appendage is reduced. This causes stasis which allows clots to form”, Sievert explains. “These clots may dislodge and embolise to the brain. In patients with atrial fibrillation, 90% of the clots form in the left atrial appendage.” The device, made of a selfexpanding alloy cage with a polymer covering, was tested on 15 patients (age 59–78 years) with chronic atrial fibrillation and at high risk for

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stroke. In a procedure called percutaneous left atrial appendage transcatheter occlusion (PLAATO), the device was inserted into the LAA with a catheter. No complications associated with the device were seen in any of the patients after more than 6 months of follow-up (Circulation 2002; published online April 8; DOI: 10.1161/01.CIR. 0000015698.54752.6D). Sievert hopes that the procedure will help patients who should not take warfarin or other anticoagulants for long periods. “The aim of the procedure is to make anticoagulant therapy unnecessary”, says Sievert. “Device implantation makes no sense if the patient has to take anticoagulant therapy also for other reasons.” W Dudley Johnson (W Dudley Johnson Heart Care Center, Brookfield, WI, USA), who holds a patent on a technique that involves stapling shut the LAA, considers the PLAATO effort important. “The stroke risk for atrial fibrillation patients is at least five times higher

than for people without atrial fibrillation”, Johnson notes. However, he adds that questions remain about the long-term effectiveness of the PLAATO procedure. The device was initially tested on dogs. In most cases, the device was covered over by the endothelial linings of the dogs’ hearts within 2 or 3 months. “We have no idea how long it will take to endothelialise in humans”, Johnson remarks. He is also concerned about the risk from infections caused by an artificial device inside the heart, and about possible damage caused by puncturing the septum of the heart by the catheter before implantation of the device. Nonetheless, Johnson finds many advantages to the PLAATO approach. Another solution, however, appeals to him. “Considering the hundreds of thousands of deaths from the atrial appendage”, said Johnson, “it makes sense to get rid of it”. David Lawrence

THE LANCET • Vol 359 •April 13, 2002 • www.thelancet.com

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