Impact of donor specific antibodies on longitudinal lung function and baseline lung allograft dysfunction.

Background: Lung transplantation offers life-saving benefits for patients with end-stage lung disease, however, long-term outcomes remain poor, with a median survival of 6.5 years. Identifying patients at risk for poor post-transplant lung function is crucial for improving outcomes. While peri-operative and demographic factors have previously been studied, the impact of donor-specific antibodies (DSA) on longitudinal post-transplant lung function remains unclear. This study examines the effects of DSA on post-transplant lung function and the risk of baseline lung allograft dysfunction (BLAD).

Research Question: Is DSA development linked to worse longitudinal lung function, higher BLAD rates, and poorer survival compared to DSA-negative patients regardless of the development of clinical AMR?

Methods: This study included lung transplant recipients from two prospective cohort studies, comparing DSA+ and DSA- patients. All participants underwent serial surveillance and clinically-indicated bronchoscopy, pulmonary function tests, and DSA testing. Statistical analysis included linear mixed models for longitudinal lung function data, multivariable logistic regression for BLAD, and survival analysis using Cox Proportional Hazard models.

Results: We analyzed 213 patients with a median follow-up of 48.1 months. Among them, 50.7% developed DSA. DSA+ patients showed significantly lower rates of post-transplant spirometric improvement compared to DSA- patients (p=0.008 for %FVC; p=0.02 for %FEV1). After DSA detection, there was a significant decrease in the slopes of %FVC and %FEV1 (p=0.0008 and p=0.0006, respectively). DSA+ patients had a higher risk of developing BLAD (OR 2.14, 95% CI [1.45, 3.17], p=0.0001). Additionally, DSA+ patients had a higher risk of death (HR 2.98, 95% CI [1.79, 4.99], p<0.0001). These findings were consistent even when excluding patients with clinical antibody-mediated rejection (AMR).

Interpretation: Our study demonstrates that DSA development significantly impairs post-transplant lung function and increases the risk of BLAD even in the absence of clinical AMR. These findings suggest that DSA may serve as a biomarker of BLAD, and could potentially aid in risk stratification following lung transplantation.