Opportunistic infections in autoimmune pulmonary alveolar proteinosis: opportunity to better understand the role of GM-CSF in the innate immune response

Autoimmune pulmonary alveolar proteinosis (aPAP) is an ultra-rare lung disease characterised by myeloid cell dysfunction, abnormal pulmonary surfactant accumulation resulting in progressive dyspnoea of insidious onset and respiratory failure, innate immune deficiency and secondary infection.1 2 Autoantibodies that bind GM-CSF (granulocyte/macrophage colony-stimulating factor) drive the pathogenesis, primarily causing alveolar macrophage dysfunction, resulting in an inability to recycle surfactant and cell debris.1 3 Secondary infections are relatively common in aPAP and can include both common and opportunistic pathogens. Infections can be present at disease onset, and indeed at times have been hypothesised to cause secondary PAP.4 Importantly, approximately one-fifth of deaths related to PAP syndrome can be related to secondary infection.4 GM-CSF signalling is central to the healthy differentiation, proliferation and maturation of alveolar macrophages, ensuring maintenance of surfactant homoeostasis and innate host defence responses. GM-CSF modulates these...

Source: Thorax - December 15, 2023 Category: Respiratory Medicine Authors: O'Callaghan, M., Penugonda, M., McCarthy, C. Tags: Thorax Editorial Source Type: research