IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG-type autoantibody production in autoimmune pulmonary alveolar proteinosis

Am J Physiol Lung Cell Mol Physiol. 2012 May 1;302(9):L959-64. doi: 10.1152/ajplung.00378.2011. Epub 2012 Feb 24.


The granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody (GMAb) is the causative agent underlying autoimmune pulmonary alveolar proteinosis (aPAP). It consists primarily of the IgG isotype. At present, information on other isotypes of the autoantibody is limited. We detected serum the IgM isotype of GMAb (IgM-GMAb) in more than 80% of patients with aPAP and 22% of healthy subjects, suggesting that a continuous antigen pressure may be present in most patients. Levels of the IgM isotype were weakly correlated with IgG-GMAb levels but not IgA-GMAb, suggesting that its production may be associated with that of IgG-GMAb. The mean binding avidity to GM-CSF of the IgM isotype was 100-fold lower than the IgG-GMAb isotype, whereas the IC(50) value for neutralizing capacity was 20,000-fold higher than that of IgG-GMAb, indicating that IgM-GMAb is only a very weak neutralizer of GM-CSF. In bronchoalveolar lavage fluid from nine patients, IgG-GMAb was consistently detected, but IgM-GMAb was under the detection limit in most patients, confirming that IgM-GMAb is functionally a bystander in the pathogenesis of aPAP. It rather may be involved in the mechanism for development of IgG-GMAb in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibody Formation
  • Autoantibodies / blood*
  • Autoantibodies / chemistry
  • Autoantibodies / physiology
  • Autoimmune Diseases / immunology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Case-Control Studies
  • Cell Count
  • Child
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / chemistry
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin G / blood
  • Immunoglobulin G / chemistry
  • Immunoglobulin M / blood*
  • Immunoglobulin M / chemistry
  • Immunoglobulin M / physiology
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Protein Binding
  • Pulmonary Alveolar Proteinosis / immunology*
  • Young Adult


  • Autoantibodies
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Granulocyte-Macrophage Colony-Stimulating Factor