Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
- Pulmonary alveolar proteinosis
- Alveolar proteinosis
- GM-CSF autoantibody
- Opportunist lung infections
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 functions via transcription factor PU.1.5 GM-CSF influences macrophage cytokine production, specifically tumour necrosis factor-α (TNF-α) and interleukin-6, which can have proinflammatory and anti-inflammatory effects through engagement of the CD14 receptor by lipopolysaccharide (LPS).6 GM-CSF knockout mice showed pathological changes similar to those seen in patients with aPAP with accumulation of surfactant phospholipids and proteins.5 These mice are more susceptible to infection, have delayed bacteria clearance and demonstrate increased mortality from infection.7 Furthermore, this is not macrophage specific as PU.1 knockout mice have impaired neutrophil and T lymphocyte development.5 Conversely, …
Contributors All authors contributed equally.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.