Pulmonary alveolar proteinosis (PAP)

Pulmonary alveolar proteinosis (PAP) is a rare disease characterised by alveolar accumulation of surfactant composed of proteins and lipids due to defective surfactant clearance by alveolar macrophages. PAP is caused by a disruption in surfactant catabolism by alveolar macrophages due to loss of functional granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. Three main categories of PAP have been defined depending on the aetiology: auto-immune, secondary, and genetic. Genetic PAP can result from mutations in CSF2RA, the gene encoding the alpha chain of the GM-CSF receptor and seen especially in children. Adult forms are mostly auto-immune (with GM-CSF antibodies) and/or secondary to toxic inhalation or hematological disorders, without anti-GM-CSF antibodies. Autoimmune PAP is the most common form (90%).

Respiratory tract disease

CSF2RA [HSA:1438] [KO:K05066]

Inhalation of inorganic dust [CPD:C19572] or toxic fumes, hematologic malignancies, pharmacologic immunosuppression, and certain infections

A similar but histopathologically distinct disorder of surfactant homeostasis can occur with mutations for the genes encoding surfactant proteins B or C [DS:H00217].

PMID:21632797 (description, gene)

Borie R, Danel C, Debray MP, Taille C, Dombret MC, Aubier M, Epaud R, Crestani B

Pulmonary alveolar proteinosis.

Eur Respir Rev 20:98-107 (2011)

PMID:20623372 (description, gene, environmental factor, comment)

Martinez-Moczygemba M, Huston DP

Immune dysregulation in the pathogenesis of pulmonary alveolar proteinosis.

Curr Allergy Asthma Rep 10:320-5 (2010)