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

Autor:	Ataya A; Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, FL, United States., Knight V; Department of Pediatrics, Section of Allergy and Immunology, University of Colorado School of Medicine and Children's Hospital, Aurora, CO, United States., Carey BC; Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Lee E; Division of Pulmonary, Critical Care, and Sleep Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States., Tarling EJ; Department of Medicine, Division of Cardiology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States., Wang T; Division of Pulmonary, Critical Care, and Sleep Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Nov 22; Vol. 12, pp. 752856. Date of Electronic Publication: 2021 Nov 22 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.752856
Abstrakt:	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. Competing Interests: AA serves on the Medical and Scientific Advisory Board of the PAP Foundation. VK received support for attending workshops, meetings, and education in leadership roles for Workshop in Primary Immunodeficiencies, College of American Pathologists, and Clinical Immunology Society, and served as President/Past President of the Association of Medical Laboratory Immunologists. BCC’s institution received an NIH-funded R01 grant related to the content of the manuscript. Outside of the current work, BC is a consultant to Partner Therapeutics, Inc. and serves on the Board of Directors and as Secretary/Treasurer of the PAP Foundation. EL’s institution received NIH-funded grants related to the content of the manuscript. EL has served as a consultant to Guidepoint Global and has received travel support from the PAP Foundation and the Rare Lung Disease Consortium. TW’s institution received a fellowship grant funded by Partner Therapeutics, Inc. TW received consultant fees from Partner Therapeutics for research outside of the current work; participated on an Advisory Board for IQVIA; and serves on the Board of Directors, Medical and Scientific Advisory Board, and as Vice President and Clinical Director of the PAP Foundation. The authors declare this study received funding from Partner Therapeutics, Inc. The funder had the following involvement with the study: Professional medical writing, graphic artist, and publication fees for this manuscript. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Ataya, Knight, Carey, Lee, Tarling and Wang.)
Databáze:	MEDLINE
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