NIH

Zebra of the Week: Autoimmune pulmonary alveolar proteinosis

September 1, 2025

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare autoimmune lung disorder and the most common form of pulmonary alveolar proteinosis, accounting for approximately 90% of cases. It’s caused by IgG autoantibodies that block granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein essential for surfactant clearance by alveolar macrophages. This disruption leads to the accumulation of surfactant (a mix of proteins and fats) in the alveoli, impairing gas exchange and causing respiratory symptoms.

Symptoms vary widely. Some individuals remain asymptomatic, while others experience progressive dyspnea, chronic dry cough, fatigue, weight loss, chest pain, and general malaise. Less common manifestations include hemoptysis, digital clubbing, and cyanosis. The disease can present from childhood through adulthood and affects fewer than 5,000 people in the U.S.

Source:

(Accessed 2025, August 29). NIH: Genetic and Rare Diseases Information Center. Autoimmune pulmonary alveolar proteinosis. https://rarediseases.info.nih.gov/diseases/7499/autoimmune-pulmonary-alveolar-proteinosis