A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics. When the gene, called UGT2B17, is missing from the donor's genome but present in the recipient's, transplants have a significantly greater risk of a serious side-effect known as graft-versus-host disease, in which immune cells from the donor attack tissues in the recipient.
"This finding gives us a glimpse into the genetic incompatibilities that can complicate transplants," said first author Steven McCarroll, an assistant professor at Harvard Medical School and an associate member of the Broad Institute of MIT and Harvard, who led the study while working as a postdoctoral fellow with David Altshuler at Massachusetts General Hospital and the Broad. "There are likely many other compatibility loci left to be found, and with the enhanced capabilities for surveying human genetic variation, it will become increasingly feasible to find them."
The basic premise behind organ and tissue transplantation is simple: remove the diseased part from one patient and replace it with a healthy counterpart from another. But there are several facets of the process that are anything but simple, including the genetic incompatibilities that can exist between donor and host tissues. Graft-versus-host disease (GVHD) is one immune-related condition that can arise as a result of these genetic mismatches.
GVHD is a common yet serious complication of bone marrow transplantation (also known as "hematopoietic stem cell transplantation"), a procedure in which blood and immune "stem cells" are isolated from a healthy person's marrow and transferred to a patient with a life-threatening disease, often cancers of the blood or immune system. As a result of the transplant, the donor's blood and immune systems are reconstituted in the reci
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Broad Institute of MIT and Harvard