Finding a transplant match for blacks.

Finding a transplant match for blacks

She was black, 19, and she needed a bone marrow transplant to treat her leukemia. But despite an exhaustive, nationwide search that went on for months, JoAnne Johnson of Washington, D.C., never found a donor whose tissue type matched hers closely enough to allow the transplant. She died last February, still waiting for the perfect match.

Molecular biologist Carolyn Katovich Hurley says her research team has now identified some of the reasons why blacks, and perhaps other minorities, have trouble finding appropriate donors for bone marrow, kidney or other transplants.

Scientists have known for years, she says, that a tissue donor and recipient must share certain antigens--inherited protein "markers" on cell surfaces--in order for the body's immune system to accept transplanted tissue as its own. While immunity-suppressing drugs such as cyclosporine can temporarily quell the rejection response, antigen matching helps ensure long-term survival of the transplanted tissue, Hurley notes.

In the case of kidney transplants, she says, a donor ideally should have two sets of three "human leukocyte antigens," or HLAs--one set inherited from each parent--that match those of the recipient. The three antigens, which have several subtypes, are known as HLA-A, HLA-B and HLA-DR.

But in a genetic study of about 200 U.S. blacks and 900 whites, Hurley and her colleagues at the Georgetown University School of Medicine in Washington, D.C., have found that one of the subtypes, called HLA-DR3, itself occurs in two different forms, only one of which exists in whites. Moreover, they discovered that 46 percent of the blacks in their study group possessed the form that is almost never found in the white population.

"Therefore, any attempts to find a matched kidney for a black individual [with this form of the subtype] among a white donor pool would be unlikely to succeed," Hurley says.

The study also revealed that blacks in the United States generally have a more diverse assortment of HLA antigens than whites, further complicating the search for appropriate donors, she says. Saulo Klahr, a kidney specialist at the Washington University School of Medicine in St. Louis, notes that several other minority groups, including Native Americans, may face similar difficulties in finding well-matched organ donors.

Hurley says HLA-typing laboratories are not yet equipped to detect the newly identified antigen subtypes. She adds, however, that her team has created a new database on HLA diversity in blacks, which gives researchers the information they need to start making new HLA-typing reagents, using short DNA pieces, or oligonucleotides, as antigen "detectors." The Georgetown investigators used such detectors, in combination with gene amplification, cloning and sequencing, to isolate and identify the HLA genes from the individuals in their study.

The new findings highlight the urgent need for more black organ donors. In 1985, 33 percent of U.S. patients with kidney failure (a condition requiring a transplant) were black, yet only 21 percent of the patients receiving kidney transplants that year were black, Hurley notes. In addition, the graft-survival rate in blacks lags 15 percent behind that in whites three years after a kidney transplant, she says. Hurley adds that several factors in addition to HLA-mismatching may explain the poorer survival rate, including the quality of medical care.

An improved understanding of HLA diversity among blacks may also help scientists study and treat autoimmune disorders such as insulin-dependent (Type I) diabetes, in which susceptibility appears linked to a person's HLA types, she adds.

Hurley next plans to study how a person's HLA makeup might affect the severity and frequency of a variety of illnesses, she told SCIENCE NEWS.