DALLAS, Texas, Aug. 25 -- A certain virus may make the body turn against itself in some children, leading to development of an enlarged heart, say scientists in today's Circulation: Journal of the American Heart Association.
Although researchers already know that inflammation can lead to idiopathic (cause unknown) dilated cardiomyopathy -- a condition in which the heart becomes enlarged and functions poorly -- there has been uncertainty about the mechanism by which the specific virus causes this sometimes fatal disease.
In a study of three children who developed myocarditis -- a heart disease triggered by infection, which precedes cardiomyopathy -- researchers found evidence that the immune system was responding in an unusually aggressive way to certain proteins called antigens. Antigens are located in viruses, and they trigger the cells in the body's immune system to respond.
The children's genetic background made them more susceptible to this virus, which led to an overreaction of the normal immune system response, making a relatively common virus -- coxsackievirus B (CVB) -- potentially deadly.
"There are many different variants of this virus and most all children are exposed to it, but they all don't develop myocarditis," says the study's senior author, Massimo Trucco, M.D., director, division of immunogenetics, Children's Hospital of Pittsburgh and professor of pediatrics of the University of Pittsburgh School of Medicine. "Fortunately, only some of these variants have certain genetic sequences that direct the virus to the target organ, in this case, the heart."
Among the various viruses, some may have a genetic sequence, which turns regular antigens into "super" antigens, powerful enough to trigger a more aggressive immune response. In the children studied, a superantigen led in part to the powerful response triggering the development of an enlarged heart. Once this form of CVB invades the body, it can cause the immune system to overreact and attack the organ where it has taken up residence.
The genetic variations in the virus tell it where to go and whether it can create a superantigen. In children who have a certain genetic makeup, Trucco says, the virus can be directed by the body to either the heart or the pancreas. "CVB is a common virus. The problem is there are literally thousands of variants of it," says Trucco. "The ones that can turn lethal are rare in the sense that only a few of the thousand or so variations can cause the disease. Many children are exposed to the more common forms of this virus, and all they have are flu-like symptoms and then they're fine. But children who are infected with these rarer forms have a much higher risk of developing cardiomyopathy."
In prior research, Trucco and his colleagues found that the same aggressive immune response may be causing children to develop juvenile diabetes. Because variations of the genetic sequences may direct the virus to different organs, Trucco applied this finding to cardiomyopathy in this most recent study and found similar results, strengthening the idea that CVB may also be a cause of juvenile diabetes.
"More research needs to be done to further prove scientifically that CVB triggers cardiomyopathy," he says. "It's possible that the genetic background of the children may also influence the susceptibility to one or the other disease."
Other studies have estimated the prevalence of dilated cardiomyopathy in the United States as about 36.5 cases per 100,000 people. The idiopathic form typically strikes early in life, and 75 percent of children who develop this disease die within five years. Viruses such as CVB are thought to be responsible for causing about half of the cases of myocarditis in North America, according to Trucco.
"It's important to remember that this is still a rare disease and that it is relatively easy to screen children for their genetic predisposition to this disease," says Trucco. "The real goal is to find the segment in the genetic coding of the virus that produces the dangerous superantigen. Once we have done this, then we then we can create a specific vaccine."
Co-authors are Patrizia Luppi, M.D.; William A. Rudert, M.D., Ph.D.; Maria M. Zanone, M.D., Ph.D.; Giorgio Stassi, M.D.; Giuliana Trucco, M.D.; David Finegold, M.D.; Gerard J. Boyle, M.D.; Pedro Del Nido, M.D.; and Francis X. McGowan Jr., M.D.