Multilamellated Basement Membranes in the Capillary Network of Alveolar Capillary Dysplasia.

A minimal diffusion barrier is key to the pulmonary gas exchange. In alveolar capillary dysplasia (ACD), a rare genetically driven disease of early infancy, this crucial fibrovascular interface is compromised while the underlying pathophysiology is insufficiently understood. Recent in-depth analyses of vascular alterations in adult lung disease encouraged researchers to extend these studies to ACD and compare the changes of the microvasculature. Lung tissue samples of children with ACD (n = 12), adults with non-specific interstitial pneumonia (n = 12), and controls (n = 20) were studied using single-gene sequencing, immunostaining, exome sequencing, and broad transcriptome profiling in addition to analysis of the vasculature by transmission electron microscopy. In ACD, pulmonary capillary basement membranes were hypertrophied, thickened, and multilamellated. Transcriptome profiling revealed increased CDH5, COL4A1, COL15A1 (collagen type 15A1), PTK2B, and FN1 and decreased VIT (vitronectin) expression, confirmed by immunohistochemistry. In contrast, non-specific interstitial pneumonia samples showed a regular basement membrane architecture with preserved VIT expression but also increased COL15A1

Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Disclosure Statement J.C.S. received fees for lectures from Boehringer Ingelheim and Kinevant, all outside the present study. T.W. declares funding by the German Ministry of Research and Education. M.M.H. received fees for lectures and consultations from Acceleron, Actelion, AOP, Bayer, Janssen, MSD, and Pfizer, all outside the present study. J.F. received personal fees/speaker honoraria from AstraZeneca, outside the submitted work. M.G. received fees for lectures from Boehringer Ingelheim, participates in an adjudication board in a nintedanib clinical trial, and received a research grant from Boehringer Ingelheim. D.D.J. received fees for lectures from Boehringer Ingelheim and declares a research contract with Boehringer Ingelheim (contract number 43099358). All other authors declare no existing conflicts of interest.