Why do some lung transplant patients face higher rejection risk?

“Lung transplantation has the poorest long-term survival of any solid organ transplant, and that’s largely because of chronic rejection,” said Dr. Hrish Kulkarni, the Allan J. Swartz and Roslyn Holt Swartz Women's Lung Health Endowed Chair and associate professor in the Division of the Division of Pulmonary, Critical Care and Sleep Medicine at the David Geffen School of Medicine. He is also corresponding author of the study, published in The Journal of Clinical Investigation. 

 “We wanted to understand why certain patients are more vulnerable to chronic lung organ rejection than others, and uncover new biological pathways that could lead to more effective therapies and, ultimately, better long-term outcomes for our patients.” 

The study analyzed two separate cohorts of lung transplant recipients and found that about one-third carried the C3 gene variant. In both groups, patients with this variant were more likely to experience chronic rejection, especially if they also had antibodies against the donor lungs. To understand why, researchers used a mouse lung transplant model with a similar predisposition to impaired complement regulation. These experiments showed that the lung rejection was caused by the complement system activating certain B cells to make antibodies that attack the transplanted lung – a process that current anti-rejection medicines cannot fully control.   

“We hope these findings pave the way for new, more personalized therapies for chronic lung rejection, a disease that currently has no cure,” Kulkarni said.  

Reference:

Hrishikesh S. Kulkarni, Laneshia K. Tague, Daniel R. Calabrese, Fuyi Liao,4 Zhiyi Liu, Lorena Garnica, Nishanth R. Shankar, Xiaobo Wu, Devesha H. Kulkarni, Impaired complement regulation drives chronic lung allograft dysfunction after lung transplantation,The Journal of Clinical Investigation, DOI: 10.1172/JCI188891