UCLA researchers in the Department of Medicine and the Department of Pulmonary and Critical Care have recently developed a novel method for diagnosing acute cellular rejection in lung transplants with increased sensitivity and specificity in comparison to previously established approaches.
BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death following lung transplants. Acute cellular rejection (ACR) is a major risk factor for developing CLAD and often precedes it. To prevent the development of CLAD, it is imperative to identify early signs of ACR in patients. Currently, the gold standard for diagnosis of ACR is via transbronchial biopsy (TBB). This procedure requires collection of a small sample of lung tissue during a bronchoscopy which is then assessed by a pathologist. However, this process is invasive, has a high incidence of sampling error, and carries a risk of morbidity due to complications such as bleeding or pneumothorax. Furthermore, inter-observer concordance amongst pathologists regarding ACR is poor. Due to this, ACR is often misdiagnosed, leading to increased risk of CLAD.
INNOVATION: Researchers at UCLA led by Dr. S. Samuel Weigt have demonstrated the use of bronchoalveolar lavage cell pellet (BAL-cp) gene expression to diagnose ACR. Unlike TBB, BAL-cp requires a less invasive procedure wherein a sterile saline solution is instilled and then recovered during a bronchoscopy. This allows collection of sample from a larger surface area of the lung, resolving issues of sampling error. The fluid is then pelleted and cells from the surface of the lung are retrieved for sequencing and downstream gene expression analysis. Using this method, researchers identified key genes associated with ACR and created a gene-based model to predict ACR with 91% accuracy. This novel and less invasive approach exhibits great potential in improving diagnostic accuracy for ACR.
POTENTIAL APPLICATIONS:
- Diagnosis of ACR
- Ability to identify early signs of CLAD
ADVANTAGES:
- Lower morbidity risk
- Less invasive diagnosis procedure (BAL-cp vs TBB)
- Improved sensitivity and specificity in diagnosis of ACR
- Leverages reduced sequencing costs due to advances in sequencing technology
- Decreased sampling error due to collection of sample from larger surface area
DEVELOPMENT-TO-DATE: The feasibility of BAL-cp gene expression for ACR diagnosis has been shown to be accurate (specificity 87.5%, sensitivity 73.3%) using multi-center adult lung transplant datasets, including an independent validation cohort.
Related Papers (from the inventors only):
Weigt, S Samuel et al. “Development and validation of a bronchoalveolar lavage genomic classifier for acute cellular rejection.” EBioMedicine vol. 122 (2025): 106046. doi:10.1016/j.ebiom.2025.106046
Keywords: acute cellular rejection (ACR), lung transplant, transplant rejection, gene expression, random forest model, bronchoalveolar lavage, chronic lung allograft dysfunction