Gender News

Heart transplant failure higher in women with common virus

by Ruth Schechter on 08/02/10 at 7:00 am

Acute rejection of a transplanted heart is higher in women than in men. A recent study by a Stanford cardiologist shows that women who have been exposed to cytomegalovirus (CMV), a common virus that lies dormant in many adults, may be part of the reason.

About 75 percent of all adults have been exposed to the virus. Although the virus causes no or mild symptoms in adults, it is dangerous to fetuses whose mothers acquire the disease when pregnant and to people with suppressed immune systems. Because CMV stays alive in the body indefinitely, the body develops antibodies against the virus, even while the disease is dormant.

In a multi-site study funded by the National Institutes for Health (NIH), Hannah Valantine, MD, a Stanford professor of cardiovascular medicine and a Clayman Institute 2009-10 Faculty Research Fellow, helped to clarify the relationship between the virus and transplant failure, and now hopes to expand the study to determine how CMV affects women in particular.

“Women with the virus are more likely to develop problems, including acute rejection of the transplanted heart,” said Valantine, who has spent much of her career studying the mechanisms behind heart transplant failure. “The question is, do sex differences affect the relationship between the virus and transplant outcome?”

Donor Heart Procurement © Vasily Kaleda/iStockPhotos

Heart transplant patients require immunosuppressant drugs to keep their T cells from attacking the new heart. However, the B cells that make CMV antibodies are produced in the bone marrow and have an indefinite capacity for memory. Once the B cells that normally produce protective antibodies against the virus have been suppressed by drugs, the virus is more likely to be reactivated and cause serious side effects.

Valantine’s studies have shown that even in the presence of CMV antibodies, immunosuppression can reactivate the virus and cause rejection. Her research points to the possibility that CMV activation leads to increased numbers of antibodies directed against the transplanted heart by the recipient. Further study is required since heart biopsies have conventionally looked for inflammatory cells, not antibodies.

“The antibodies mount an attack against the transplanted heart,” said Valantine. “Women are most prone to producing these antibodies since they may be more likely to be exposed to the virus when pregnant.”

Valantine also is participating in the Clinical Trials in Organ Transplantation project, a new interdisciplinary, multi-site NIH study, to assess several drugs in reducing presensitization of patients to human leukocyte antigens (HLA) before a transplant.

Hannah Valantine, MD, speaks on gender in cardiovascular medicine on iTunes

“It’s routine to look at HLA antibodies before a transplant to avoid certain donors,” she said. “However, we’re finding that the rates of presensitization are higher in women, so they may be at greater risk for transplant failure. That means that women are more likely to wait for a match. We need to see if woman are being treated differently—there’s a huge emphasis to see how we can better select patients for transplant to prevent rejections.”

Valantine, who is also the medical school’s senior associate dean for diversity and leadership, has been conscious of the role of gender in medicine throughout her career. “I found my gender and race were actually an advantage when I was starting out because women were so rare in cardiology at the time,” she said. “Today, however, we need a robust pipeline for women in medicine to shape research on gender differences in disease outcomes. At the very least, doctors should represent the proportions of minorities and women among their patients.”