title: Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis.
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 cryptococcal 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-1α 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.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lindsey B
authors.initials: LB
authors.lastname: Rosen
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Yang
authors.forename: Kamonwan
authors.initials: K
authors.lastname: Jutivorakool
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
authors.forename: Nasikarn
authors.initials: N
authors.lastname: Angkasekwinai
authors.forename: Yupin
authors.initials: Y
authors.lastname: Suputtamongkol
authors.forename: John E
authors.initials: JE
authors.lastname: Bennett
authors.forename: Vasilios
authors.initials: V
authors.lastname: Pyrgos
authors.forename: Peter R
authors.initials: PR
authors.lastname: Williamson
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Browne
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood* / Q000502:physiology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D008297:Male; D016919:Meningitis, Cryptococcal / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D050799:STAT5 Transcription Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor