Transplantation Medicine Organ rejection preventable in the long term

Rejection reaction after organ transplantation prevented

Transplants are always associated with the risk that the body of the recipient will reject the donated organ. Researchers have now been able to prevent this rejection reaction in a kidney transplant.

Enormous progress in transplantation medicine

Transplantation medicine has made tremendous progress in recent years. For example, in 2015 the medical scientists succeeded in achieving the sensational transplantation of a skullcap. And last year, the first penile grafting was done in the US. Also causing a stir was a recent operation by a German-Italian team of scientists, in which a boy was transplanted an almost completely new skin. Even more striking, however, is the project of an Italian surgeon: he is planning the first human head transplantation. The problem with all forms of transplantation of organs is the risk that the body rejects the foreign tissue. However, researchers have now been able to prevent this rejection reaction - in animals - in a transplantation.

Transplants always run the risk of the body rejecting the donated tissue. Researchers have now succeeded in preventing this rejection reaction. (Image: Kadmy / fotolia.com)

Prevent rejection reaction of the recipient

The immunologist Prof. dr. Marcus Groettrup from the University of Konstanz and his research group have developed a way to prevent rejection reactions in rats following kidney transplantation and to suppress the production of antibodies against the transplanted organ in the immune system of organ recipients.

The crucial role is played by the inhibition of the immunoproteasome, which suppresses the production of antibodies, it said in a statement.

The results of the research group have now been published in the journal "Kidney International".

So far, there is hardly an effective drug defense

According to the experts, about ten years after a kidney transplant, about half of the transplant kidneys are repelled by antibodies. Against this chronic rejection, there is hardly any effective drug defense.

Although non-selective proteasome inhibitors can suppress the rejection of transplants caused by antibodies, they are only of limited use due to strong negative side effects.

However, immunoproteasome inhibitors have been shown to be effective in preclinical models of autoimmune diseases and have been administered for weeks without obvious side effects.

Production of antibodies suppressed

In a rat model, the scientists led by Marcus Groettrup have shown that inhibiting the immunoproteasome kills the activated plasma cells that produce the antibodies against the transplant kidney.

Selective immunoproteasome inhibition by inhibitor ONX 0914 reduced the number of B and plasma cells and suppressed the production of the antibody specific to the donor.

The transplants were obtained from a urological surgeon from the Cancer Institute Chongqing in China, Dr. Ing. Jun Li, who works as a fellow of the Chinese Scholarship Council at the University of Konstanz and is an international microsurgery expert.

Promising therapy approach

"The results are a complete success. We can completely prevent the rejection in all animals and see that the antibodies that are formed against the transplant organ are virtually eliminated, "says Groettrup.

"The inflammatory parameters in the transplanted kidney have declined markedly and the renal function of the recipients is excellent," summarizes the expert, explaining that these findings suggest that immunoproteasome inhibition may be a promising therapeutic approach in the treatment of chronic antibody-induced rejection.

Groettrup's structural model of the immunoproteasome is considered fundamental to the development of drugs against autoimmune diseases such as diabetes, rheumatoid arthritis and multiple sclerosis.

At the beginning of the 2000s, Groettrup succeeded in identifying the immunoproteasome as a regulator of precisely those messengers that cause autoimmune diseases.

A pharmaceutical development of inhibitors that specifically eliminate the immunoproteasome would allow a fight against autoimmune diseases and organ donation recipients without at the same time weakening the entire immune system of the body. (Ad)