Tissue Rejection 101

Why the first face transplant might not stick.

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The Frenchwoman who received a historic face transplant in November nearly rejected her new mug, her doctors said Tuesday. As her immune system attacked the transplanted skin, the new face turned red. Doctors staved off the problem with a huge dose of steroids, and now the patient is doing well enough to resume smoking cigarettes. Why do transplanted body parts get rejected?

Because the human immune system is designed to attack anything it doesn’t recognize. White blood cells recognize the body’s tissues by looking for a set of antigens on the surface of each cell. The most important of these make up the major histocompatibility complex. When your immune system finds cells in your body that don’t show the right MHC proteins, it tries to destroy them.

Doctors test the MHC of potential organ donors to find the best match. (They also test for blood type.) The test focuses on six important MHC antigens, which can be identified from a master list that includes hundreds of possibilities. * The chances of a perfect match—where the donor had the same six as the recipient, for example—are very small. The closer the match, the better the success rate for the transplant. (Identical twins, who share the same MHC profiles, never reject each other’s tissues. *)

Finding a good match can reduce the severity of tissue rejection, but transplant doctors always expect some degree of immune response. The rejection can take one of several forms. In hyperacute rejection, the body immediately begins to fight off the foreign tissue, and symptoms appear almost immediately after the operation. Acute rejection can occur over a period of weeks or months, and chronic rejection takes hold over a span of years.

A rejected organ can suffer direct damage and cell death from the immune system, and it can be damaged by a loss of circulation. Physical signs of rejection include inflammation (like the redness in the Frenchwoman’s new face), an overall feeling of illness, and specific signs of organ failure. A reduction in urine might signal a rejected kidney, and a yellowish skin tone suggests a rejected liver.

Doctors use immunosuppressants to treat (and prevent) tissue rejection. All recipients take the drugs, which are often given even before the operation takes place. Tests of tissue compatibility determine the doses used—a worse MHC match might call for more medication. Anyone who’s on these drugs is likely to be on them for her whole life, although the doses are kept low as long there’s no acute rejection.

There are other anti-rejection treatments. The doctors in France transplanted the face donor’s bone marrow in the hopes that it would provide the transplantee with immune cells that recognized the new face. The procedure runs the risk of giving her one more thing to reject. It could also lead to a condition called “graft vs. host disease,” in which T-cells from transplanted bone marrow reject the body into which they’ve been transplanted.

Bonus Explainer: Some organs are easier to transplant than others. The degree of difficulty depends in part on how much access the immune system has to that organ. Corneal transplants, for example, tend to have high success rates because of the cornea’s relative isolation within the body.

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* Correction, January 25, 2006: This piece originally stated that identical twins sometimes reject each other’s tissues; this never happens. It also implied that each person expresses only six different MHC antigens. Though there are more, tissue tests generally focus on six. Click here to return to the corrected paragraph.