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. Burlinghams 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 mothers HLA type with those of
the transplant candidates 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
NIAIDs 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).
References:
New England Journal of Medicine
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).
Journal