Altered macrophage phenotypes in a case of autoimmune pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is an ultra-rare disease characterised by abnormal accumulation of surfactant components in the alveoli [ 1 ]. The majority of cases are of an autoimmune nature (previously named primary or idiopathic) and are linked to the presence of an autoantibody targeting granulocyte–macrophage colony-stimulating factor (GM-CSF) [ 1 ]. This anti-GM-CSF antibody impedes the ability of alveolar macrophages to remove pulmonary surfactant. As a consequence, a significant proportion of patients experience progressive respiratory failure and immune deficiency [ 1 ]. While considerable progress has been made in understanding the pathophysiology of PAP over the past two decades, there has yet to be an in-depth analysis of macrophage phenotypes in human lungs with PAP. Our study reports on a case of PAP and presents a novel approach to analysing macrophage phenotypes in this condition using mass cytometry. Mass cytometry of BALF cells from a pulmonary alveolar proteinosis patient, positive for anti-GM-CSF antibodies, suggests potential impairment in human alveolar macrophage differentiation https://bit.ly/45JHUrz