The ingenious technique of kidney transplantation in children leads to impaired immunity

Organ transplants can literally save lives, but they are also accompanied by strings – a lifelong immunosuppressive drug that is often required to test the immune system so that it rejects the transplanted organ as a foreign invader.

Scientists are now reporting three successful kidney transplants in children in California without the need for immune pressure. Transplants used a new method that reduced the risk of new kidney failure.

This means freedom from immunosuppressants and related side effects, which are not always pleasant (and increase the risk of cancer and diabetes). It also reduces the chances of requiring a second transplant due to the rejection of the first transplant.

Alice Berthaine, an associate professor of pediatrics at Stanford University in California, says patients can survive lifelong immunosuppression after a kidney transplant.

The innovative technique works by safely transplanting the donor’s immune system to the patient through the bone marrow stem cells – even before the kidneys warm up: a double immune / solid organ transplant or DISOT. This has been tried before, but has been successful.

An additional process has been added here. The researchers made depletion of alpha-beta T cells and CD19 B cells, which meant the destruction of anti-host disease or immune cell types that caused GVHD – a potential death threat to development when similar methods were used. used before.

When the risk of GVHD was reduced, the process was much safer. Because the removal of alpha-beta T cells is relatively “soft,” it makes it suitable for medically vulnerable children and allows for partially genetically matched transplants (parenting). The resulting cells regenerate naturally in the patient within 60-90 days and rebuild the immune system.

Other changes have been made, including reducing the toxicity of chemotherapy and radiation required prior to transplantation. However, some very difficult preparatory work is required to prepare the body to break down the patient’s immune system and adopt a new organ.

Three children who received a kidney transplant in this way have a very rare genetic disease called Pim-Immune-Ossetian Dysplasia (SIOD), which limits the body’s ability to fight infection and causes kidney failure.

“This remarkable experience underscores the potential of joint or sequential hematopoietic stem cell transplantation and kidney transplantation to correct hematopoietic and immune deficiencies and develop tolerance to kidney allograft,” writes Massachusetts Chief Medical Officer Massachusetts of Massachusetts. .

“SIOD is a rare disease involving immune deficiency, which has certainly contributed to the success of successful donor HSCT engraftment.”

SIOD and all its difficulties remain something that children have to deal with, and now they have kidney owners and are working as they are. Researchers say the transplant was successful for at least 22 and 34 months.

“These were unique patients in whom we had to transplant a stem cell and a kidney,” Berthaina said.

“They’re doing everything: going to school, going on vacation, playing sports. They’re living a normal life.”

The next step is to increase the number of patients and the number of conditions in which this can work, as it is currently only available to patients with SIOD, making them particularly suitable for the procedure.

Of particular interest to the study group were patients who were rejected by the body after a kidney transplant. This happens in up to half of all cases in children, which leads to hypersensitivity of the immune system, which does not accept a second kidney through a routine transplant procedure.

Children are the first to benefit, and then researchers work until adulthood. Finally, this technique can be adapted for transplantation of organs other than the kidneys, but this takes some time.

“It’s a challenge, but it’s impossible,” Berthaina says.

Published in a research journal New England Journal of Medicine.


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