New transplant findings fit like a glove.

New transplant findings fit like a glove

This year, more than 10,000 kidneytransplants will be performed in the United States, according to the National Kidney Foundation. But despite recent advances in immunosuppressive therapy (SN: 6/28/86, p.407), approximately 20 percent of these transplants will result in rejection--most of them in patients who at some time in their past have tested positive for human lymphocytic, or HLA, antibodies.

Physicians have known for years that apatient with HLA antibodies specific to a donor's HLA antigens is much more likely to reject that donor's transplanted organ. Indeed, with donated kidneys in short supply, anyone who has ever tested positive for these antibodies is considered a poor candidate for the lifesaving surgery--even if, as often happens, their antibodies inexplicably disappear at some point. Surgeons willing to perform transplants on such "historically positive' but currently HLA-negative patients have been frustrated by their inability to understand why some of these grafts are in fact very successful, while others are almost immediately rejected.

Recently, however, researchers havefound evidence of a multi-tiered anti-antibody system that not only explains why HLA antibodies sometimes disappear, but also identifies HLA-converted patients for whom transplants will probably succeed. Like a series of bigger and bigger gloves fitting over an original hand, the anti-antibodies and anti-anti-antibodies --both known as anti-idiotypic antibodies--apparently will either block or potentiate a patient's original HLA antibodies. Their discovery, reported in the June 4 NEW ENGLAND JOURNAL OF MEDICINE, may lead to changes in the way patients are tested for organ compatibility and could lessen the uncertainty inherent in the transplant business, scientists say.

The research team, led by Elaine Reedat Columbia University's College of Physicians and Surgeons in New York City, performed retroactive blood tests on 20 kidney recipients with histories of antibody sensitization to their donor's HLA antigens. Half the patients rejected their transplants within 30 days, but the remaining 10 patients' grafts survived at least one year, despite no apparent significant differences between the two groups' immunological compatibility. With further testing, however, the researchers found that nine of 10 patients whose grafts were successful showed evidence of anti-antibodies capable of blocking their original HLA antibodies. Moreover, nine out of 10 of the patients who rejected their grafts showed evidence of anti-anti-antibodies, which seem to overwhelm the anti-antibodies, thereby reinstituting the original immune reaction.

"This is the most important finding Ican think of to explain the loss of antibody in some sensitized [kidney transplant] patients, and to explain why some patients do well and others do not,' Reed says. The test will be of particular benefit, she suggests, to the approximately 30 percent of would-be transplant recipients with a history of being highly sensitized to HLA antigens. Anti-idiotypic antibody testing, she says, will show that many of these patients who have until now been considered poor transplant candidates may in fact be ideal recipients. Similarly, would-be recipients who at first appear to be donor-compatible but who harbor undetected anti-anti-antibodies can be identified and spared the medical and economic expense of a transplant that is almost certainly doomed.

Thomas Fuller, a blood transfer specialistwho is doing related research at Massachusetts General Hospital in Boston, says Reed's findings are significant not only because they open the door to better compatibility testing, but also because they may lead to sophisticated ways to induce antibody-specific immunosuppression in transplant recipients. "We all hope that someday we'll know enough about the immune system apparatus to allow us to manipulate it,' he says. "If we could design or stimulate production of anti-idiotypic antibodies, it would probably allow transplants for many of the patients who have antibodies that now preclude them from getting organs.' Such capabilities, he says, are still years away.

Meanwhile, Reed says of the two-hourtest, "to have a tool that tests for an antibody associated with rejection is very important. Our goal is to implement these tests as routine clinical procedures on all our kidney transplants.'