Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis

Lindsey B. Rosen, Alexandra F. Freeman, Lauren M. Yang, Kamonwan Jutivorakool, Kenneth N. Olivier, Nasikarn Angkasekwinai, Yupin Suputtamongkol, John E. Bennett, Vasilios Pyrgos, Peter R. Williamson, Li Ding, Steven M. Holland, Sarah K. Browne

Research output: Contribution to journalArticle

Abstract

Cryptococcal meningitis has been described in immunocompromised patients, as well as in those for whom no immune defect has been identified. GM-CSF regulates the function of phagocytes and pulmonary alveolar macrophages, critical elements in cryp-tococcal control. We performed clinical histories, immunological evaluation, and anticytokine autoantibody screening in four current patients with cryptococcal meningitis and identified and tested 103 archived plasma/cerebrospinal fluid samples from patients with cryptococcal meningitis. We assessed the ability of anti-GM-CSF autoantibody-containing plasmas to inhibit GM-CSF signaling. We recognized anti-GM-CSF autoantibodies in an otherwise healthy female with cryptococcal meningitis who later developed pulmonary alveolar proteinosis (PAP). Her diagnosis prompted screening of patients with cryptococcal meningitis for anticytokine autoantibodies. We identified seven HIV-negative patients with cryptococcal meningitis who tested positive for high-titer anti-GM-CSF autoantibodies. Two of the seven later developed evidence of PAP. Plasma from all patients prevented GM-CSF-induced STAT5 phosphorylation and MIP-1a production in normal PBMCs. This effect was limited to their IgG fraction. Anti-GM-CSF autoantibodies are associated with some cases of cryptococcal meningitis in otherwise immunocompetent patients. These cases need not have associated PAP.

Original languageEnglish (US)
Pages (from-to)3959-3966
Number of pages8
JournalJournal of Immunology
Volume190
Issue number8
DOIs
StatePublished - Apr 15 2013

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rosen, L. B., Freeman, A. F., Yang, L. M., Jutivorakool, K., Olivier, K. N., Angkasekwinai, N., Suputtamongkol, Y., Bennett, J. E., Pyrgos, V., Williamson, P. R., Ding, L., Holland, S. M., & Browne, S. K. (2013). Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis. Journal of Immunology, 190(8), 3959-3966. https://doi.org/10.4049/jimmunol.1202526