When Kaitlyn Sinnamon was 20 weeks pregnant with her second child, doctors told her that her baby would be born with a heart condition that would require surgery early in her life.
Easton Sinnamon was born at Duke University Hospital in the United States with single-ventricle heart disease, which meant his heart had only one ventricle, instead of two, to pump blood to the rest of his body.
After two heart surgeries failed to fix a leaky heart valve related to his congenital heart disease, it became clear to the surgical team that Easton would need a new heart. But the transplant would require Easton to take immunosuppressive drugs for the rest of his life so his body wouldn’t reject the new organ.
These drugs can increase the risk of cancer and be toxic to the kidneys, as well as making patients more susceptible to serious infections.
But doctors faced another challenge as Easton awaited a heart transplant. After repeated infections, further tests revealed that he had a deficiency in a specific type of immune system cell called a T cell. T cells mature in the thymus, an organ that sits in front of the heart.
Easton’s poor immune function meant his body didn’t naturally produce T cells, which are also often responsible for the body rejecting and attacking a transplanted organ when it doesn’t recognize it.
“It was a fluke in the sense that Easton needed a heart transplant and also had very poor immune function,” said Dr. Joseph Turek, chief of pediatric cardiac surgery at Duke University and a member of Easton’s surgical team, at a news conference Monday.
This made Easton a candidate for further surgery to receive a new heart and processed thymus from the same donor. This combination of procedures had never been done on a human being.
For Easton’s parents Kaitlyn and Brandon Sinnamon, the decision to have their baby undergo such critical procedures was not an easy one, especially given the risks that come with transplant surgery. When Easton’s second surgery failed, Turek discussed options with the Sinnamons.
“I think one of the things that struck us the most is that he told us, ‘I want to save your son, and the only way to do that is through a transplant,'” Kaitlyn Sinnamon told CNN. “’If it works, it will not only help Easton, but millions of other people as well. And besides, we will make a huge difference. And if it doesn’t work, at least we tried.”
According to Turek, Duke University is the only place in the Western Hemisphere that does cultured thymus transplants, in which the donor’s thymus cells are incubated and grown in the laboratory before being implanted into the recipient.
In a healthy immune system, immature immune cells enter the thymus, where they learn to identify what is “self” and what is foreign. The thymus culture process cleans up any of the donor’s mature immune cells, leaving a thymus structure for the recipient to develop its own immune cells.
“It’s the idea that the thymus is growing in the same environment as the new transplanted organ, that’s what allows us to recognize it as ‘I’. If you just use the thymus and don’t grow it, you already have cells that would start to reject it,” Turek told CNN.
Easton’s immune deficiency meant he could develop one aspect of his immune system – T cells – as his body got used to his new heart. This double transplant from the same donor may even eliminate the need for lifelong dangerous immunosuppressive drugs.
In August, at age 6 months, Easton had a heart transplant and began taking immunosuppressive medication. Two weeks later, after the cells from the donor thymus had completed the culturing process, he also received the thymus implant.
“It’s bittersweet to be excited about your son’s transplant because you can bring him home, but someone else is losing theirs,” Sinnamon said.
Shortly after the surgery, Easton was taken out of the intensive care unit, which indicated to his parents that he was recovering well.
Six months after the transplant, tests showed that Easton’s new thymus was properly developing T cells and that his body had not rejected his new heart. These results are promising, and Easton’s medical team hopes to wean him off his immunosuppressant medication within a year, if tests confirm that his T cells recognize his transplanted heart as his.
“The idea that you could have a transplant and not have to take these drugs is really a game-changer for organ transplant patients,” Turek told CNN.
Turek also said the success of this procedure could mean the transplanted heart could live longer.
Currently, transplanted hearts usually only survive 10 to 15 years because of minor episodes of rejection in the years after the procedure. These episodes can usually be treated by increasing the dosage of immunosuppressive drugs, but they can ruin the integrity of the heart over time.
Therefore, building an immune system that is tolerant of a heart transplant can increase the durability of that heart.
Turek sees this as an opening to the future of transplant medicine. The next step is to test whether this procedure can be successful in someone with a healthy immune system who needs an organ transplant.
“I think if that happens, that’s how most transplants are going to be done in the future, and that’s going to be in every organ,” Turek told CNN.
However, T cells are only part of the immune system’s response to transplanted organs, noted Dr. Reshma Biniwale, associate professor of cardiac surgery and director of pediatric heart transplantation at UCLA.
“I would be very hesitant to say that the child will be completely free of any immunosuppression, because this technique only takes care of the T cells, the thymic cells,” said Biniwale, who was not involved in Easton’s surgery.
“Immunity is also mediated by antibodies from humoral cells, which require a completely different mechanism of immunosuppression.”
B cells, also known as humoral cells, are a type of immune cell that produces antibodies and are produced in the bone marrow.
“This may be a great short-term solution, but it doesn’t offer a lifetime solution,” Biniwale told CNN.
It remains unclear whether this procedure would be feasible in an adult patient, according to Turek, because the thymus shrinks as people age and the bone marrow becomes responsible for producing T cells.
“That’s one of the things we’re looking at in the lab, as well as figuring out what the appropriate age of the donor is. We believe it will likely be somewhere in early adulthood where you would still have a viable thymus for transplantation,” Turek said.
There is even the potential for transplants of cultured thymus to accompany xenotransplantation, which is when organs from animals are transplanted into humans.
A man who was the first to receive a genetically modified pig heart transplant died on Tuesday, two months after the surgery. Turek says a cultured thymus transplant can eliminate the need for high doses of the immunosuppressive medication the man needed.
Seven months after his own surgeries, Easton celebrated his first birthday and “is thriving at home,” according to Sinnamon.
“When we brought him home, he couldn’t even lift his head. We had to carry him like a newborn baby, and now he’s walking around the house, laughing and playing with his sister on the floor,” she said. “If you looked at him now, you would have no idea he went through what he went through.”
Source: CNN Brasil
