Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRα gene in the X chromosome pseudoautosomal region 1

Margarita Martinez-Moczygemba, Minh L. Doan, Okan Elidemir, Leland L. Fan, Sau Wai Cheung, Jonathan T. Lei, James P. Moore, Ghamartaj Tavana, Lora R. Lewis, Yiming Zhu, Donna M. Muzny, Richard A. Gibbs, David P. Huston

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common β chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR α chain, encoded in the X-chromosome pseudoautosomal region 1.

Original languageEnglish (US)
Pages (from-to)2711-2716
Number of pages6
JournalJournal of Experimental Medicine
Volume205
Issue number12
DOIs
StatePublished - Nov 12 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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