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Title: Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis
Authors: 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
National Institute of Allergy and Infectious Diseases
Washington University School of Medicine in St. Louis
Chulalongkorn University
Mahidol University
Keywords: Immunology and Microbiology
Issue Date: 15-Apr-2013
Citation: Journal of Immunology. Vol.190, No.8 (2013), 3959-3966
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. Copyright © 2013 by The American Association of Immunologists, Inc.
ISSN: 15506606
Appears in Collections:Scopus 2011-2015

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