The Role of GM-CSF Autoantibodies in Infection and Autoimmune Pulmonary Alveolar Proteinosis: A Concise Review

Abstract

Autoantibodies to multiple cytokines have been identified and some, including antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), have been associated with increased susceptibility to infection. High levels of GM-CSF autoantibodies that neutralize signaling cause autoimmune pulmonary alveolar proteinosis (aPAP), an ultrarare autoimmune disease characterized by accumulation of excess surfactant in the alveoli, leading to pulmonary insufficiency. Defective GM-CSF signaling leads to functional deficits in multiple cell types, including macrophages and neutrophils, with impaired phagocytosis and host immune responses against pulmonary and systemic infections. In this article, we review the role of GM-CSF in aPAP pathogenesis and pulmonary homeostasis along with the increased incidence of infections (particularly opportunistic infections). Therefore, recombinant human GM-CSF products may have potential for treatment of aPAP and possibly other infectious and pulmonary diseases due to its pleotropic immunomodulatory actions.

GM‐CSF antibodies in artificial stone associated silicoproteinosis: A case report and literature review

“…Secondary PAP is linked to a relative deficiency of GM‐CSF leading to either reduction in the number or function of alveolar macrophages, or both. 2 , 3 , 10 Inhalation of high levels of toxic particles such as silica impair alveolar macrophage function through direct toxicity. 11 , 12 Acute exposure to extremely high levels of silica has also been found to lead to excess production of surfactant and proteinaceous exudate from type II alveolar epithelial cells and may also contribute to the development of acute silicoproteinosis.…”

“…It is produced by multiple cell types including alveolar epithelial cells, macrophages and lymphocytes. 2 , 10 As a colony stimulating factor it maintains adequate production and differentiation of granulocytes and macrophages via phosphorylation of STAT5 and subsequent activation of multiple intracellular signalling pathways. 5 GM‐CSF also has additional effects on immunity through enhancing neutrophil bactericidal function and macrophage function through increased antigen presentation and phagocytosis.…”

“… 5 GM‐CSF also has additional effects on immunity through enhancing neutrophil bactericidal function and macrophage function through increased antigen presentation and phagocytosis. 10 It has additional roles in host defence by promoting leukocyte migration via the production of numerous pro‐inflammatory cytokines. 2 , 10 …”

“… 10 It has additional roles in host defence by promoting leukocyte migration via the production of numerous pro‐inflammatory cytokines. 2 , 10 …”

“…10 It has additional roles in host defence by promoting leukocyte migration via the production of numerous proinflammatory cytokines. 2,10 In relation to PAP, GM-CSF promotes the differentiation of alveolar macrophages in the human lung which serve to clear pulmonary surfactant and debris from the alveoli. 10 Reduced numbers and function of alveolar macrophages from low GM-CSF results in surfactant accumulation within alveoli.…”