Ingenious technique allows children to have kidney transplants without immune suppression

Organ transplants can literally save lives, but they also come with strings attached – often including a lifetime of immunosuppressive drug treatments needed to control the immune system lest it reject the transplanted organ as a foreign invader. .

Today, scientists report three successful kidney organ transplants, performed on children in California, without the need for immune suppression. The transplants used a new method that minimizes the risk of rejection of the new kidney.

This means the absence of immunosuppressants and the associated side effects, which are not always pleasant (and include an increased risk of cancers and diabetes). It also reduces the risk that a second transplant will be needed due to rejection of the first.

“It is possible to safely release patients from lifelong immunosuppression after kidney transplantation,” says Alice Bertaina, associate professor of pediatrics at Stanford University in California.

The innovative technique works by safely transplanting the donor’s immune system into the patient – via bone marrow stem cells – before the kidney also moves: Double Immune/Solid Organ Transplantation or DISOT. This has been tried before, but with limited success.

Here, an additional process has been added. The researchers performed alpha-beta T-cell and CD19 B-cell depletion, which meant eliminating the types of immune cells that cause graft-versus-host disease, or GVHD – a life-threatening complication that could develop when similar techniques have been used. been used in the past.

With a reduced threat of GVHD, the process was much safer. The removal of alpha-beta T cells is relatively “gentle”, making it suitable for medically vulnerable children, and it allows for genetically half-matched transplants (from one parent). The removed cells naturally recover in the patient within 60-90 days, thereby replenishing the immune system.

Other adjustments were made, including a reduction in the toxicity of chemotherapy and radiation therapy needed before the transplant. Still, quite grueling prep work is required to knock out the patient’s immune system and prepare the body to receive a new organ.

The three children transplanted in this way suffer from an extremely rare genetic condition called Schimke’s immuno-osseous dysplasia (SIOD), which limits the body’s ability to fight infections and can lead to kidney failure.

“This remarkable experiment underscores the potential of combined or sequential hematopoietic stem cell transplantation and kidney transplantation to correct hematopoiesis and immunodeficiency disorders and to induce renal allograft tolerance,” Thomas writes. Spitzer and David Sachs of Massachusetts General Hospital in an accompanying editorial. .

“SIOD is a rare disease that involves immunodeficiency, which undoubtedly contributed to the successful donor HSCT transplant.”

Although SIOD and all of its complications are still a problem children have to deal with, they are now all owners of kidneys that work as they should. The transplants were successful for at least 22 and 34 months, the researchers report.

“These were unique patients in whom we had to perform a stem cell transplant and a kidney transplant,” says Bertaina.

“They do everything: they go to school, they go on vacation, they play sports. They lead a completely normal life.”

The next steps are to increase the number of patients and the number of conditions for which it could work, as at the moment it has only been shown in patients with SIOD, making them particularly suitable for the procedure.

The research team is particularly interested in patients who have already had a kidney transplant that their body rejected. This happens in almost half the cases in children, resulting in an over-sensitized immune system that would likely not accept a second kidney as part of a normal transplant procedure.

Children will be the first to benefit from it, then researchers will work until older ages. Eventually, the technique could even be adapted to cover organ transplants other than kidneys, but this will take time.

“It’s a challenge, but it’s not impossible,” says Bertaina.

The research was published in the New England Journal of Medicine.

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