Managing a miracle: Addressing immune responses to organ transplants

A successful organ transplant is the treatment for many end-stage diseases. The result? Usually, an improved quality of life and prognosis — but it is a process not without its own set of potential pitfalls to keep an eye out for. One of these is organ rejection, or the risk of the patient’s body refusing the transplanted organ.

Headshot of Christine Lin
Christine Lin, MD, Clinical Assistant Professor, Department of Medicine, Division of Pulmonary

“Understanding transplant immunology is important for all solid organs,” said Christine Lin, MD, an assistant professor of medicine in the division of pulmonary, critical care and sleep medicine. “After all, you are asking your body to accept an organ from someone who is not yourself and even with correct medications, there is always a chance that your body can reject it.”

Chronic rejection is the leading cause of organ transplant failure and is marked by a long-term loss of function due to fibrosis, or scarring, of the organ. Unfortunately, this process is poorly understood, Lin said. The biological basis behind the self-sabotaging function makes sense: The body recognizes the transplanted organ as foreign to the recipient, and can make short work of it. Although immunosuppressants exist for this reason, they are generally nonspecific, suppressing large parts of the immune system and leaving the patient vulnerable.

“Immunosuppressive medications work well,” Lin said. “And we need them to. But they are associated with side effects and leave patients more likely to develop infections or malignancies, which can also affect longevity among transplanted organs.”

With lungs in particular, there’s a different kind of risk.

“Lungs are open to the environment,” Lin explained. “Organs like the kidney, liver and heart are relatively protected, but with the lungs, you’re constantly breathing and therefore expose them to everything from allergens and pollutants to infections.”

Ideally, Lin said, researchers will be able to construct a more targeted approach, allowing one to minimize the risk of rejection, while still allowing the body to maintain a normal immune system by performing its normal tasks such as fighting infections, or destroying cancer cells.

“When you’re studying transplant immunology, it’s really a study of how to not only alter the recipient’s immune system to accept the organ as its own, but to also work with that immune system so that it functions as it was designed to,” Lin said.

Lin’s work focuses on the current how and why this process occurs, parsing out the fine mechanisms behind which of these organs get rejected and what triggers that. Using animal models, she researches how the immune system’s various components can promote scarring and fibrosis and dysfunction of the organ.

“Once we understand the underlying mechanisms, we can look to more precise and targeted therapies,” Lin said. “Right now, what we do is almost like taking a sledgehammer to a very small nail.  It is not very elegant, but science is working to change that.”

A nurse stands across from a double lung transplant patient. Both wear masks.
Jessica (left), a nurse who grew close to Jill (right) throughout her hospitalization, bids her farewell. Jill is one of more than 19 COVID-19 patients who have received new lungs from UF Health’s nationally recognized lung transplant team.

For now, Lin and a team of pulmonary transplant specialists help patients optimize their miracles to carry their improved quality of life for years to come.

“At UF Health, we identify potential recipients and give them the support they need for their best chance at doing well,” Lin said. “We are always looking at the big picture, and in doing so, hope to maximize their quality of life and their long-term outcomes.”

In a way, she said, patients are learning to manage and adjust to a lifelong condition.

“We’re committed to helping them, and a large part of that is conducting the research necessary to move the needle for what exceptional care looks like,” Lin said.