Organ transplantation. The end of incompatibility?

By Aude Rambaud – Le Figaro 

What if organ donor-recipient incompatibility was no longer a problem? What if a patient who couldn't find a suitable kidney, lung, or heart could receive one from any donor, regardless of their immune system and without risk of rejection?

The idea is not new, and the technique of desensitizing the receptor is already practiced in the United States and Europe, including France, but in a rather reserved manner. Now, for the first time, a study published in New England Journal of Medicine This shows that this strategy ends up having its price on a large scale, in patients who are unlikely to receive a transplant: eight years after a kidney transplant, 76,5% of people who benefited from this desensitization are still alive, compared to 63% of those who were able to benefit from a compatible transplant and 44% of those who are still waiting for a suitable graft.

The notion of compatibility

To understand the challenges, let's go back to this notion of compatibility. Each individual carries a molecular signature in all the cells of their body, as if it were a kind of fingerprint. This signature, called the HLA system, is what allows our immune system to recognize our own cells in relation to foreign cells to be eliminated. For a graft to work, the HLA system must be as close as possible between a donor and a recipient. In fact, each person has antibodies against HLA codes that are not their own and that attack foreign cells. But, about 15 to 20% of patients have so many that they automatically reject all grafts within hours or days after transplantation.

A desensitization protocol

For these specific patients, doctors began developing a desensitization protocol about twenty years ago, allowing them to accept any graft. This involves eliminating all antibodies from their body before transplantation, including anti-HLA antibodies, through plasma filtration, followed by treatment to prevent their recurrence. The patient is also deprived of much of their own immunity, and in return, receives "good" antibodies to protect them from infections. Once the new organ is transplanted, the patient undergoes immunosuppressive treatment to prevent the antibody stock from replenishing. And if necessary, further plasma filtration can be performed later.

But the technique is lengthy and requires several days of preparation so that the organ is available in a timely manner. For the kidney, doctors rely on a living donor. For other organs (lungs, heart, liver), the patient may be placed at the beginning of a waiting list to receive a graft first.

A heavy cost for hospitals to bear.

In France, the technique is practiced in nine transplant centers (Grenoble, Toulouse, Saint-Étienne, Bordeaux, Strasbourg, Paris Necker, Paris Tenon, Paris Saint-Louis, and Rouen), but in a very limited way, as the cost is too high for hospitals to bear: approximately 30 euros more for the graft. In five years, about sixty patients have benefited from the transplant in France.

In theory, they could be more numerous: of more than 15 patients waiting for a kidney transplant in 2015, about 2 were unlikely to be transplanted because of the abundance of these notorious anti-HLA antibodies. "This technique provides good results, but there's a form of self-censorship because of the cost. We can't offer it to everyone," laments Lionel Rostaing, a kidney transplant physician at the University Hospital of Grenoble. Furthermore, some doctors are still reluctant because of uncertainties about the renal viability of these apparently incompatible grafts, or even about the risk of developing cancer due to immunosuppression, the specialist points out. But the study of New England Journal of Medicine This shows that this strategy is effective in the medium term for patients whose life expectancy is quite limited in the absence of transplantation. I hope, therefore, that this will convince decision-makers to develop this option, even if it means using an older and cheaper filtering method, so that more patients can benefit.