Aug. 26, 2003 ROCHESTER, Minn. -- A long-standing medical discussion about how transplanted organs survive in a new body has received provocative new evidence from Mayo Clinic research. It shows a donated kidney survives in a new body by turning on a protective mechanism to shield it from the hostile environment of the patient's immune system. The results are published in this month's American Journal of Transplantation.
Says Mark Stegall, M.D., head of the transplant team that studied kidney genes' response to transplantation, "The big question has always been: Why don't the antibodies injure the kidney? Our study begins to show one possible reason for that -- there's a protective mechanism at work."
In the study, the Mayo Clinic team analyzed which genes are turned on during the biological phenomenon known as "accommodation" -- the process by which a transplanted organ adapts to the new environment of the donor's body. Accommodation was first described 20 years ago by Jeffrey Platt, M.D., a Mayo Clinic transplant biologist and co-author of this current Mayo Clinic study.
James Gloor, M.D., a Mayo Clinic nephrologist and research team member, describes the significance of the work this way: "It's not that the recipient's immune system fails to see the organ; it's more that the organ, in some way, can turn on this protection that allows it to inhabit this otherwise hostile environment of a new body."
An Accommodation Analogy: Calluses and Blisters
Transplant surgeons want to get to the heart of the accommodation mechanism so they can manipulate it most effectively and gently. Their goal is to provide the patient maximum benefit in a transplant with the least side effects.
Says Dr. Gloor, "In biology, most of the time the body can protect itself from a variety of things." He offers the example of how feet protect themselves from the friction of new shoes that cause blisters by producing protective skin thickenings: calluses. "Once your feet have calluses, you can walk around with your shoes and you don't develop blisters anymore. The reason you can is that your foot has accommodated to that hostile environment," he says.
Drs. Stegall and Gloor say a similar protective response appears to occur during kidney transplantation. For example, when one kidney is removed from the donor, that leaves the donor with a single functioning kidney which senses that it needs to do more work. "We can see it will get bigger so it can do more work. It's compensating for the fact that it's the only one there,'' Dr. Gloor explains.
To try to observe the mechanisms at work in accommodation, the Mayo Clinic team used a molecular biological technique that allowed them to look at which genes were expressed in kidney transplants in which the donor's and patient's immune systems were compatible. They then contrasted the compatible-transplant gene expression patterns with genes expressed in kidney transplants that were immunologically incompatible.
Different gene-expression patterns occurred in different situations. Says Dr. Stegall, "We found that there was a wide array of entirely different genes turned on -- or turned off -- in the incompatible transplants that were not changed in regular kidney transplants. It implies that something is happening in the incompatible kidney. From the results, it seems likely that the kidney is 'accommodating' to the otherwise destructive antibodies by developing processes that actually protect it." Accommodation, he adds, may actually be a fairly general phenomenon present in a variety of human diseases.
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