Ultrastructure as a Diagnostic Adjunct in the Evaluation of Lung Allograft Biopsies

Abstract

Humoral immunity contributes significantly to lung graft dysfunction. Recognizing a role of ultrastructural studies in the evaluation and diagnosis of chronic humoral allograft rejection in the kidney, the authors sought to explore its utility as a diagnostic adjunct in lung allograft biopsies. Ultrastructural studies were conducted on 44 biopsies from 26 lung transplant recipients. Endothelial cell activation and necrosis were seen in the setting of acute humoral allograft rejection. Septal chronic vasculopathic changes of thickening and lamellation of the basement membrane zone (BMZ) and BMZ collagen deposition were correlated with greater numbers of humoral allograft rejection episodes and with the development of chronic graft dysfunction/bronchiolitis obliterans syndrome. There was a positive correlation between the extent of septal fibrosis and certain chronic vasculopathic changes, namely collagen deposition in the BMZ and BMZ wrinkling. Patients with chronic graft dysfunction and multiple rejection episodes manifested low diffusion capacities (less than 50% predicted). The results indicate that ultrastructural analysis is useful in identification of septal fibrosis and chronic vasculopathy of the septal microvasculature, correlating with chronic graft dysfunction, encompassing not only fibrotic sequelae of the bronchial wall but also irreversible terminal lung parenchymal changes, the latter associated with repeated episodes of humoral rejection.