title: Human guanylate binding protein-1 is a secreted GTPase present in increased concentrations in the cerebrospinal fluid of patients with bacterial meningitis.
abstract: Interferon-gamma-induced GTPases are key to the protective immunity against microbial and viral pathogens. As yet, the cell interior has been regarded as the exclusive residence of these proteins. Here we show that a member of this group, human guanylate binding protein-1 (hGBP-1), is secreted from cells. Secretion occurred in the absence of a leader peptide via a nonclassical, likely ABC transporter-dependent, pathway, was independent of hGBP-1 GTPase activity and isoprenylation, and did not require additional interferon-gamma-induced factors. Interestingly, hGBP-1 was only secreted from endothelial cells but not from any of the nine different cell types tested. Clinically most important was the detection of significantly (P<0.001, Mann-Whitney U-test) increased hGBP-1 concentrations in the cerebrospinal fluid of patients with bacterial meningitis (n=32) as compared to control patients (n=74). In this first report of a secreted GTPase, we demonstrate that secreted hGBP-1 may be a useful surrogate marker for diagnosis of bacterial meningitis.
authors.affiliation: Department of Surgery, Division of Molecular and Experimental Surgery, Institute for Clinical Microbiology, Immunology, and Hygiene, Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Naschberger
authors.forename: Clara
authors.initials: C
authors.lastname: Lubeseder-Martellato
authors.forename: Nadine
authors.initials: N
authors.lastname: Meyer
authors.forename: Ruth
authors.initials: R
authors.lastname: Gessner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Andrè
authors.initials: A
authors.lastname: Gessner
authors.forename: Michael
authors.initials: M
authors.lastname: Stürzl
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D003937:Diagnosis, Differential; D020558:GTP Phosphohydrolases / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology; D017368:Protein Prenylation / Q000276:immunology; D014777:Virus Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000276:immunology
chemical_list: D015415:Biomarkers; C490287:GBP1 protein, human; D007371:Interferon-gamma; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins