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

Ali Ataya,Vijaya Knight,Brenna C Carey,Elizabeth J Tarling,Elinor Lee,Tisha Wang

doi:10.3389/fimmu.2021.752856

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.

Highlights

Autoantibodies (AAbs) against cytokines are detectable in the plasma of both healthy and diseased individuals, but the role and potential pathology of anti-cytokine autoantibodies are not fully known [1]
High levels of AAbs that neutralize granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling cause autoimmune pulmonary alveolar proteinosis, an ultrarare autoimmune disease characterized by accumulation of excess surfactant in the alveoli, leading to pulmonary insufficiency
The results suggest the potential for studying GM-CSF therapy in the treatment of serious infections associated with autoimmune pulmonary alveolar proteinosis (aPAP)

Summary

Introduction

Autoantibodies (AAbs) against cytokines are detectable in the plasma of both healthy and diseased individuals, but the role and potential pathology of anti-cytokine autoantibodies are not fully known [1]. Alveolar macrophages from patients with aPAP were determined not to be deficient in either the production of GMCSF or GM-CSFR function; they have a decreased bioavailability of GM-CSF due to the presence of GM-CSF AAbs and negative regulation by IL-10 [67, 68].

Results

Conclusion