Organ transplantation has significantly revolutionized the treatment of patients with organ failure. However, the recipient's immune system recognizes transplanted organs as foreign and elicits a defensive response that can lead to serious complications. Bronchiolitis obliterans syndrome (BOS) is one such complication that arises frequently following lung transplantation (LT) and hematopoietic stem cell transplantation (HSCT). BOS is characterized by the narrowing of airways, fibrosis, and inflammation in the lung tissue leading to breathing difficulties and poor graft survival.
Immune mechanisms and shared pathological and morphological features related to post-LT and post-HSCT BOS have been widely explored. However, why some patients develop BOS while others don't, and underlying genetic determinants that may influence responses to the respective diseases and treatments remain unknown.
To bridge this gap, researchers from Pusan National University, Korea, led by Assistant Professor Yun Hak Kim, analyzed genetic variants in lung tissues from patients who developed BOS following LT or HSCT. Their findings recently published in The Journal of Heart and Lung Transplantation were made available online on May 26, 2025. Giving further insight into their work, Dr. Kim explains, "We discovered a specific genetic variation in a gene called FCGBP that is strongly linked to bronchiolitis obliterans syndrome and poor outcomes following lung transplantation. By using genetic testing, doctors can find out which patients are at a higher risk for complications following transplantation ahead of time and implement timely preventive measures."
The researchers performed whole genome sequencing (WGS) on DNA isolated from patient-derived lung tissues and blood samples and analyzed the data for genetic variants including single nucleotide polymorphisms or changes in a single nucleotide (SNPs), insertions and deletions, and base substitutions. SNPs were the most common variant in both patient cohorts, with 731 SNPs in patients with post-LT BOS and 990 SNPs in patients with post-HSCT BOS. Additionally, patients with post-HSCT BOS had a higher mutational burden compared to those with post-LT BOS. Mutations in the FCGBP and POM121 genes were shared by patients with post-LT and post-HSCT BOS and were present in the lung tissue and blood samples. The FCGBP variant was selected for subsequent analyses given its high frequency in patients with BOS and its potential role in regulating mucosal immunity in the lung tissue. Notably, patients with the FCGBP variant were more likely to experience recurrent BOS, infections, and acute rejection mediated by an increase in donor-specific antibodies, cumulatively increasing the disease's burden and risk of death.
These findings imply that screening for FCGBP can help identify high-risk patients and devise timely and personalized immunosuppressive treatments. Further, understanding its precise role in immune regulation can aid the development of novel drugs that protect the lung tissue and improve patients' long-term outcomes.
"By testing for this genetic variation before or shortly after the transplant, doctors can adjust the treatment plan, monitor patients more closely, and take preventive steps to reduce the risk of complications like BOS. In the future, this gene variant could also be screened in routine blood tests to track transplant health and guide long-term care more effectively," Dr. Kim adds.
