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Scientists Spot Key to Kidney Transplant Success
Date:9/26/2007

A tough-to-detect antibody explains why even 'matched' organs get rejected

WEDNESDAY, Sept. 26 (HealthDay News) -- Researchers say a newly discovered immune factor is associated with kidney-transplant rejections and may explain why otherwise well-matched organs end up being rejected.

"Our paper showed that if a patient has this MICA antibody, that is very dangerous," said Dr. Yizhou Zou, study lead author and assistant professor of internal medicine at the University of Texas Southwestern Medical Center at Dallas.

"Current tests cannot see this antibody, so, this suggests that it may be very useful to add antibody screening to current screening tests," he noted.

The study is published in the Sept. 27 issue of the New England Journal of Medicine.

According to the U.S. National Institutes of Health, more than 9,000 kidney transplants are performed in the United States each year, making it second only to corneal transplants as the most common transplant operation.

More than 73,000 people are on the waiting list for a kidney, making successful transplantation critical.

However, for a kidney transplant to have even a hint of success, the donor and the recipient must be compatible. Donors and recipients can be incompatible in two ways: because of a blood type incompatibility or because of human leukocyte antigens (HLA) antigen sensitization.

HLAs, which are found on the surface of nearly every cell in the human body, help tell the difference between normal body tissue and foreign substances. Antigens vary from person to person, and HLA typing helps determine how many antigens a donor shares with a recipient. If individuals are not HLA matches, the recipient may produce antibodies to the antigen, thus spurring organ rejection.

But even donor-recipient pairs who are HLA matches can end in rejection. That has suggested that other -- as yet unknown -- antigens might be involved.

"The question was why is there a rejection, when the donor and recipient were an HLA match?" Zou said.

Major-histocompatibility-complex class I-related chain A (MICA) antigens can also stimulate antibody production and, the authors hypothesized, they might also contribute to organ rejection. The MICA antigen is found on endothelial cells, or the layer of cells lining the inside of blood vessels.

The trouble is, MICA antigens can't be detected with the methods normally used.

"Normal tests cannot see this antibody, so, we started to investigate this antibody, [to see] whether it was involved in kidney transplant rejection," Zou said.

Zou's group had previously identified MICA antibodies in transplant recipients, so they developed a test to screen for the antibody.

For this study, Zou and his colleagues tested blood samples from 1,910 recipients of kidney transplants from deceased donors, looking for anti-MICA antibodies. The blood samples came from the University of Heidelberg in Germany, which keeps a large database on transplant donors and recipients.

Antibodies against MICA were detected in 11.4 percent of the patients. The presence of these antibodies was also associated with rejection of the new kidney.

The rate of transplanted organ survival over a year for recipients with anti-MICA antibodies was 88.3 percent, versus 93 percent for those without the antibodies.

Among first-time recipients of a kidney, the organ survival rate was even lower among those with antibodies (87.8 percent) than those without antibodies (93.5 percent).

And among those with good HLA matching, having anti-MICA antibodies was associated with poorer organ survival (83.2 percent versus 95.1 percent among those without the antibodies).

"There was a very strong positive association with the MICA antibody and rejection," Zou said. "That was a surprise for us."

It's not clear yet that the anti-MICA antibody causes the organ rejection, but these findings strongly suggest that this is the case.

According to an accompanying editorial, "HLA remains the cornerstone of transplantation immunology." However, detection of MICA antigens and their corresponding antibodies may represent "a new tool set for understanding the rejection of kidney transplants," the editorial authors wrote.

"I think this is definitely a potentially useful tool in monitoring patients for increased risk of rejection," said Dr. Mohanram Narayanan, assistant professor of internal medicine with the Texas A&M Health Science Center College of Medicine and chief of the Section of Clinical Transplantation for Scott & White. After standard blood and HLA typing, "this would be a third thing to look at to make sure they're not at risk for rejection," he said.

The practice probably will not become routine right away, however, Narayanan added.

"We don't quite understand how people develop antibodies, so this is a good test on paper, but we don't really know who are the people who are at risk of developing antibodies," he said. "We need to do more studies to show what are the potential factors that cause patients to develop antibodies. It's something that you probably should look at, but I think we still have a lot more to understand about how it occurs."

More information

Read more about organ transplantation at the United Network for Organ Sharing.



SOURCES: Yizhou Zou, M.D., assistant professor, internal medicine, University of Texas Southwestern Medical Center at Dallas; Mohanram Narayanan, M.D., assistant professor of internal medicine, Texas A&M Health Science Center College of Medicine, and chief, section of clinical transplantation, Scott & White; Sept. 27, 2007, New England Journal of Medicine


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