Researchers at the University of Pennsylvania School of Medicine have found an association between the genetics of donor-recipient matches in kidney transplants and complications during the first week after transplantation.
The team, led by Malek Kamoun MD, PhD, Professor of Pathology and Laboratory Medicine and Director of the Clinical Immunology and Histocompatibility Laboratory, and Harold Feldman MD, MSCE, Professor of Medicine and Epidemiology, has shown that small differences in the building blocks of cell-surface proteins used to match donors and recipients for deceased-donor kidney transplantation was associated with an increased risk for delayed allograft function, or DGF.
The investigators published their findings this week online in the Proceedings of the National Academy of Sciences.
DGF is a common (30 to 50 percent incidence), but severe, malfunction of the transplant requiring dialysis in the first week after implantation, and has been associated with an increased risk of allograft rejection. In 2007, there were over 10,500 deceased-donor kidney transplants in America, according to the United Network for Organ Sharing.
"If we can validate the association we found in a larger dataset, then the genetic data can potentially be used to better match donors and recipients, thereby decreasing the level of immunosuppressants needed," notes Kamoun. "The ultimate goal is to overcome the need for strong immunosuppressants. With immunosuppression comes an increased risk for infection and cancer, among other significant complications."
The cause of DGF is poorly understood, with both non-immunological factors such as cause of death, donor age, recipient race, and immunological factors, playing a role. "But most studies haven't clearly shown an association between the HLA-specific cell-surface proteins and DGF," says Kamoun. "We have shown that amino acid variations in HLA-A proteins are associated with DGF."
HLA cell-surface proteins allow the body to identify itself to avoid autoimmune reactions. Every person has a unique HLA signature. HLA proteins also identify foreign invaders in the body. "Their primary purpose is to distinguish, self versus non-self," explains Kamoun. "That's why we need to immunosuppress recipients following transplantation."
The researchers looked at genetic variations in recipient and donor HLA proteins from blood samples (blood cells express HLA proteins) taken from 697 kidney transplant recipients and their deceased donors to obtain paired samples.