Hopkins researchers identify transplantation antigens among Sioux Indians

January 07, 2004

Efforts to increase organ donation among Native Americans may get a boost from research by Johns Hopkins scientists that is identifying the specific genetic makeup of the HLA system of human transplantation antigens among different Indian tribes. HLAs, or human leukocyte antigens, are proteins on the surface of white blood cells and are used to determine the suitability of a match between an organ donor and recipient.

The Native American population has one of the greatest needs for organ donors because of a high incidence of diabetes and end-stage renal disease, yet many are reluctant to donate a kidney because of a belief that they need to take their body intact to the spiritual world when they die. If they donate, many believe, their spirit will be restless.

Researchers with the Johns Hopkins Immunogenetics Laboratory say characterizing the specific HLA genes among different Indian tribes will identify their similarities and differences with other populations, helping to ensure compatible organ transplants. Their new report, published in the January issue of the journal Human Immunology, identifies two new alleles, or alternate gene forms, among the Lakota Sioux tribe.

"Because so many Native Americans volunteered to be in this study, we hope that their awareness of the value of tissue compatibility may make the message of donation more welcome," says Mary S. Leffell, Ph.D., lead study author and professor and director of the Hopkins laboratory. "Our study provides the first look at the HLA proteins and alleles present among the Sioux people at a time when their need for transplantation is rapidly increasing. The findings show that there is a much higher probability of finding a really good organ match among other Native Americans than among other racial/ethnic groups. Certain Asian populations share some of the same HLA proteins as the Sioux and also could be good donor choices."

For the study, the research team looked at two tribes of the Lakota Sioux - the Cheyenne River and the Ogala Sioux - residing on the Cheyenne River and Pine Ridge reservations in South Dakota. Pine Ridge is in the southwest corner of the state, close to the Badlands, while the Cheyenne River reservation is located in the north central part of the state along the Missouri River. These reservations cover some of the poorest counties in the nation, with an unemployment rate of more than 80 percent in some areas and many people living below the federal poverty level. The Sioux have one of the fastest growing rates of type 2 diabetes in the United States, Leffell says.

"The rate of end-stage renal disease among Native American tribes is from 3.5 to 20 times that of Caucasian or other populations," she says. "Despite the alarming growth in kidney disease, kidney transplant as an option has not increased proportionately."

Leffell and colleagues analyzed blood samples that had been collected from 302 Lakota Sioux volunteers. Of the participants, 263 (87 percent) claimed full American Indian ancestry through both maternal and paternal grandparents. The study group included 25 nuclear families. The research was conducted after obtaining resolutions of support from the Tribal Councils and approval from the Aberdeen Area Institutional Review Board of the Indian Health Service.

The researchers found several alleles at high frequency among the Lakota Sioux that also are prevalent in other Native Americans and Alaskans. They found another allele that previously had only been described in the Navajo and Tlingit tribes, as well as two new alleles observed only among the Sioux. In addition, the team identified among the Sioux the two most common extended haplotypes, or groups of alleles thought to be inherited together.

One of the immediate clinical applications of their research, Leffell says, is an estimation of the likelihood of finding unrelated, compatible donors for transplantation. Among the Lakota Sioux, 85 percent had HLA types that appeared unique; therefore, the remaining 15 percent could expect to find an exact match among potential organ donors within their population.

"Native Americans have higher compatibility compared to other populations, and it should be easier to find a match within their own group," Leffell adds. "We hope this knowledge will remove some barriers to donation within the tribes."

The study was conducted as part of a series of workshops initiated in 1992 by members of the American Society for Histocompatibility and Immunogenetics to provide a thorough characterization of the immunogenetics among minority populations. It was funded in part by the National Institute of Allergy and Infectious Diseases. Study coauthors were M. Daniele Fallin, Brian A. Iglehart and Andrea A. Zachary of Hopkins, and William H. Hildebrand and Joshua W. Cavett of the University of Oklahoma.
Leffell, M.S. et al, "HLA Alleles and Haplotypes Among the Lakota Sioux: Report of the ASHI Minority Workshops, Part III", Human Immunology, January 2003, Vol. 65, Issue 1, pages 78-89.

Immunogenetics Laboratory at Johns Hopkins

Human Immunology

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Johns Hopkins Medicine

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