Complement (C3a) Levels are Increased in the Bronchoalveolar Lavage Fluid of Patient with All Chronic Lung Allograft Dysfunction Phenotypes

Abstract

Purpose Humoral immunity and complement activation are thought to play a role in the pathogenesis of chronic lung allograft dysfunction (CLAD). Here we investigate C3a levels in the bronchoalveolar lavage (BAL) fluid from patients with bronchiolitis obliterans syndrome (BOS) and restrictive chronic lung allograft dysfunction (rCLAD). Methods Spirometry and bronchoscopy were obtained per protocol on lung transplant recipients at the University of Michigan. C3a was quantified using ELISA and analyzed as ng/mL of BAL fluid. Patients with an isolated FEV1 decline to ≤80% post-transplant baseline were analyzed as BOS and patients with a concurrent FVC decline at time of FEV1 decline were analyzed as rCLAD. Results We included 86 samples in our analysis: 23 were collected prior to CLAD diagnosis (mean 921 days, range 91-4111), 39 were collected near CLAD onset (range 56 days before to 90 days after lung function decline), and 28 were collected after CLAD diagnosis (mean 1073 days, range 376-2962). Prior to CLAD onset, the average C3a level was 2.55±4.28 ng/ mL, however this increased dramatically near CLAD onset to 17.7±23.9 ng/ mL (p=0.003), and remained elevated after developing CLAD at 15.2±13.9 ng/ mL (p Conclusion BAL complement levels are increased upon developing both BOS and rCLAD and remain elevated after developing CLAD. These findings indicate ongoing activation of the complement regardless of CLAD phenotype.