Research has shown that infiltrating B cells in the lungs is one of the most common complications in lung transplants and can lead to rejection. Published In Clinical Research Journal.
Approximately 2,500 people undergo lung transplants each year, according to the U.S. Department of Health and Human Services, and according to the National Institutes of Health, lung transplants are one of the few treatment options available for patients with end-stage respiratory failure.
Ischemia/reperfusion injury — damage caused by cell death after blood flow is restored to donor lungs — is one of the most common complications of lung transplant surgery and a fundamental problem facing all organ transplants, he said. Ankit Bharat, MBBSMethods, the Harold L. and Margaret N. Professor of Surgery and director of the Cunning Thoracic Research Institute, and co-author of the study.
“When you remove an organ, it goes into a state of ischemia, where you basically lose blood flow,” Bharat said. Northwestern University Robert H. Lurie Comprehensive Cancer Center“Reattachment and resumption of blood flow is called reperfusion. This happens in every organ transplant and can cause many problems, from very mild damage to the lung to complete lung failure. We don't really understand why.”
In this study, the researchers used in vivo imaging to track the activity of B cells (white blood cells known to regulate immune responses) after ischemia/reperfusion injury in mice.
The study found that B cells that infiltrate the lungs worsen lung function by producing more white blood cells (monocytes) and promoting the leakage of neutrophils, another type of white blood cell that acts as the body's first line of defense, into the surrounding tissues. The researchers also confirmed the findings in human lungs after transplantation.
The study established the critical role of B cells in ischemia/reperfusion injury and lung transplant rejection, Bharat said.
“What we've found here really delves into these intermediate processes that occur between transplantation and injury or potential primary graft dysfunction,” Bharat said.
“These findings essentially highlight the important role of B cells. What we want to do now is target these cells to prevent primary graft failure.”
Bharat said FDA-approved drugs that target B cells already exist, but more research is needed to understand whether these drugs would be effective in lung transplant patients.
“As this paper shows, we believe that not only are B cells detrimental to ischemia/reperfusion injury, but these B cells may also engraft in newly transplanted lungs and cause long-term lung dysfunction,” Bharat said. “We now need to focus our broader research to understand how B cells enter the lung immediately after transplantation, what role they play, and whether they can improve long-term survival in lung transplant patients by mitigating chronic rejection, not just immediately after transplantation, which is increasingly being recognized in our work and others as being driven by B cells.”
This research was supported by National Institutes of Health grants R01HL147290, R01HL145478, and R01HL147575.
