Back to Search Start Over

Pathogenesis-driven treatment of primary pulmonary alveolar proteinosis

Authors :
Sara Lettieri
Francesco Bonella
Vincenzo Alfredo Marando
Alessandro N Franciosi
Angelo Guido Corsico
Ilaria Campo
Source :
European Respiratory Review, Vol 33, Iss 173 (2024)
Publication Year :
2024
Publisher :
European Respiratory Society, 2024.

Abstract

Pulmonary alveolar proteinosis (PAP) is a syndrome that results from the accumulation of lipoproteinaceous material in the alveolar space. According to the underlying pathogenetic mechanisms, three different forms have been identified, namely primary, secondary and congenital. Primary PAP is caused by disruption of granulocyte−macrophage colony-stimulating factor (GM-CSF) signalling due to the presence of neutralising autoantibodies (autoimmune PAP) or GM-CSF receptor genetic defects (hereditary PAP), which results in dysfunctional alveolar macrophages with reduced phagocytic clearance of particles, cholesterol and surfactant. The serum level of GM-CSF autoantibody is the only disease-specific biomarker of autoimmune PAP, although it does not correlate with disease severity. In PAP patients with normal serum GM-CSF autoantibody levels, elevated serum GM-CSF levels is highly suspicious for hereditary PAP. Several biomarkers have been correlated with disease severity, although they are not specific for PAP. These include lactate dehydrogenase, cytokeratin 19 fragment 21.1, carcinoembryonic antigen, neuron-specific enolase, surfactant proteins, Krebs von Lungen 6, chitinase-3-like protein 1 and monocyte chemotactic proteins. Finally, increased awareness of the disease mechanisms has led to the development of pathogenesis-based treatments, such as GM-CSF augmentation and cholesterol-targeting therapies.

Details

Language :
English
ISSN :
09059180 and 16000617
Volume :
33
Issue :
173
Database :
Directory of Open Access Journals
Journal :
European Respiratory Review
Publication Type :
Academic Journal
Accession number :
edsdoj.7a5a23858374066a828728417bf2b73
Document Type :
article
Full Text :
https://doi.org/10.1183/16000617.0064-2024