Researchers Think They've Found The Cause Of Organ Rejection In Transplant Patients

Jun 26, 2017

An organ transplant can be a life-saving procedure for people with serious medical conditions, but the drugs used to ensure the patient’s immune system doesn’t reject the organ can have severe side effects.

Because the drugs suppress the immune system, they can increase the risk of infections. They can also heighten the risk of cancer and increase cholesterol and blood pressure, which can lead to a heart attack or stroke.

And even with such medications, approximately 50 percent of all transplanted organs are rejected within 10 to 12 years, according to Fadi Lakkis, scientific director of the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh.

“In an ideal world, you’d like to give a patient an organ and have it survive for the rest of their lives, especially if it’s a younger person,” Lakkis said. “But even with older people, let’s say someone in their 50s who needs an organ transplant, you’d like to see this organ last 25, 30 or 40 years.”

A new discovery from Pitt, in collaboration with the University of Toronto, could help doctors prevent organ rejection long term.

The human immune system is made up of two parts: the innate immune system and the adaptive immune system. The innate immune system is the immunity we are born with and the first line of defense, but it doesn’t do the heavy lifting of fighting infection. That job is left to the adaptive immune system.

Researchers have long understood how adaptive immunity contributes to the rejection of donor organs, but it's the innate immune system that activates the adaptive system and tells it to reject the organ in the first place. Understanding how the innate immune system itself is activated was the goal of the team’s work.

Through experiments with mice who received heart, kidney and bone marrow transplants, researchers identified a protein called SIRP-alpha that can bind to receptors on white blood cells, setting off a chain reaction that leads to organ rejection.

“Once these cells are activated, then they turn around and activate the rest of the immune system, and that leads to the full-blown rejection of the organ,” Lakkis said.

He hypothesized that this binding occurs when the SIRP-alpha protein present in the recipient’s body is different from the SIRP-alpha present in the donated organ. Lakkis said the next step is to figure out how many different variations of SIRP-alpha exist within humans.

“What we would like to do is sequence the SIRP-alpha gene in many humans who are donors and recipients of organ or bone marrow, and then ask whether a mismatch affects the outcome after transplantation,” Lakkis said.

He said it is possible that a better SIRP-alpha match could reduce the chances of organ rejection. Thus, in theory, people who receive an organ with the same SIRP-alpha as that present in their own body might be able to take fewer immune-suppressive drugs.

“It’s not a black and white, yes or no, you can get the organ,” Lakkis said. “It’s more of an intelligent way of how much immune-suppression to give.”

Colleen Sullivan with the Center for Organ Recovery and Education said transplant recipients already feel a good deal of pressure to take care of their bodies and the “gift” they’ve received, particularly when the donor is deceased.

“They do everything they can do to honor that donor," she said. "Knowing that rejection is something that’s not on the table, that would be tremendously huge for recipients to go about their lives not worrying if this transplant’s going to fail.”

The study was published Friday in the journal Science Immunology.