Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis

Lindsey B. Rosen, Nuno Rocha Pereira, Cristóvão Figueiredo, Lauren C. Fiske, Roseanne A. Ressner, Julie C. Hong, Kevin S. Gregg, Tracey L. Henry, Kirk J. Pak, Katherine L. Baumgarten, Leonardo Seoane, Julia Garcia-Diaz, Kenneth N. Olivier, Adrian M. Zelazny, Steven M. Holland, Sarah K. Browne*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Background. Nocardia species cause infections in both immunocompromised and otherwise immunocompetent patients, although the mechanisms defining susceptibility in the latter group are elusive. Anticytokine autoantibodies are an emerging cause of pathogen-specific susceptibility in previously healthy human immunodeficiency virus-uninfected adults, including anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies with cryptococcal meningitis. Methods. Plasma from patients with disseminated/extrapulmonary nocardiosis and healthy controls was screened for anticytokine autoantibodies using a particle-based approach. Autoantibody function was assessed by intranuclear staining for GM-CSF-induced STAT5 phosphorylation in normal cells incubated with either patient or normal plasma. GM-CSF-mediated cellular activation by Nocardia was assessed by staining for intracellular cytokine production and intranuclear STAT5 phosphorylation. Results. We identified neutralizing anti-GM-CSF autoantibodies in 5 of 7 patients studied with central nervous system nocardiosis and in no healthy controls (n = 14). GM-CSF production was induced by Nocardia in vitro, suggesting a causative role for anti-GM-CSF autoantibodies in Nocardia susceptibility and dissemination. Conclusions. In previously healthy adults with otherwise unexplained disseminated/extrapulmonary Nocardia infections, anti-GM-CSF autoantibodies should be considered. Their presence may suggest that these patients may be at risk for later development of pulmonary alveolar proteinosis or other opportunistic infections, and that patients may benefit from therapeutic GM-CSF administration.

Original languageEnglish
Pages (from-to)1017-1025
Number of pages9
JournalClinical Infectious Diseases
Volume60
Issue number7
DOIs
StatePublished - 1 Apr 2015
Externally publishedYes

Keywords

  • GM-CSF
  • adult-onset immunodeficiency
  • anticytokine autoantibodies
  • nocardiosis
  • opportunistic infection

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