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ShareDec. 7, 1998 — Researchers supported by the National Institutes of Health (NIH) have discovered that cellular markers, or human leukocyte antigens (HLA), on maternal tissue can provide valuable information for identifying the most suitable donors for individuals in need of kidney transplants. The new finding was reported Dec. 3, 1998, in The New England Journal of Medicine by a team of scientists led by William J. Burlingham, Ph.D., of the University of Wisconsin, Madison, and Michael A. Bean, M.D., of Dendreon Corporation, Mountain View, Calif.
"The simple addition of maternal HLA typing," says Dr. Burlingham, "to the routine family workup for living-related kidney donation will greatly expand the pool of optimal donors, by giving an alternative choice to the transplant surgeon in cases where an HLA-identical sibling is unavailable. Based on this finding, the University of Wisconsin plans to add maternal HLA typing to their pre-transplantation procedures."
To minimize the risk of transplant rejection, surgeons try to find donors who are genetically similar to the recipient. The best outcomes are achieved when the donor is the identical twin of the individual who needs a transplant. In the absence of an identical twin, other siblings, such as those who share identical HLA genes, usually provide the closest HLA match.
Dr. Burlingham's research team compared transplant survival rates of kidneys donated by HLA-identical siblings of recipients with those donated by siblings who shared only half of the recipients' HLA antigens. The researchers found that long-term survival rates of HLA-identical kidneys were the same as HLA-mismatched kidneys, provided the donors' mismatched HLA antigens were inherited from the siblings' mother rather than their father. Therefore, comparing the mother's HLA type with those of the transplant candidate's siblings will provide clues about which sibling would be the optimal organ donor.
The researchers hypothesize that prenatal exposure to maternal HLA molecules induces a long-lasting form of immune tolerance. Thus, when the recipient encounters the same HLA molecules in adult life via a sibling-donated kidney, this state of induced immune tolerance prevents rejection of the mismatched kidney.
"Finding ways to induce immune tolerance to foreign tissue is the 'Holy Grail' of transplantation researchers," notes Steve Rose, Ph.D., chief of NIAID's genetics and transplantation branch. "This study could provide important new insights into mechanisms of immune tolerance."
This study was supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIAID and NIDDK are components of the NIH, an agency of the U.S. Department of Health and Human Services.
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References:
WJ Burlingham, AP Grailer, DM Heisey, FHJ Claas, D Norman, T Mohanakumar, DC Brennan, H DeFijter, T VanGelder, JD Pirsch, HW Sollinger and MA Bean. The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors. NEJM 339, 1657-64 (1998).
F Sanfilippo. Transplantation tolerance - the search continues (editorial). NEJM 339, 1700-02 (1998).
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