Human Guanylate Binding Protein-1 Is a Secreted GTPase Present in Increased Concentrations in the Cerebrospinal Fluid of Patients with Bacterial Meningitis

Elisabeth Naschberger^*, Clara Lubeseder-Martellato, Nadine Meyer^*, Ruth Gessner, Elisabeth Kremmer, Andrè Gessner and Michael Stürzl^*

From the Department of Surgery,^* Division of Molecular and Experimental Surgery, and the Institute for Clinical Microbiology, Immunology, and Hygiene, University of Erlangen-Nuremberg, Erlangen; and the Department of Virus-Induced Vasculopathy and GSF-Service Unit Monoclonal Antibodies and Cell Sorting, GSF-National Research Center for Environment and Health, Munich, Germany

Interferon- ${gamma}$ -induced GTPases are key to the protective immunityagainst microbial and viral pathogens. As yet, the cell interiorhas been regarded as the exclusive residence of these proteins.Here we show that a member of this group, human guanylate bindingprotein-1 (hGBP-1), is secreted from cells. Secretion occurredin the absence of a leader peptide via a nonclassical, likelyABC transporter-dependent, pathway, was independent of hGBP-1GTPase activity and isoprenylation, and did not require additionalinterferon- ${gamma}$ -induced factors. Interestingly, hGBP-1 was onlysecreted from endothelial cells but not from any of the ninedifferent cell types tested. Clinically most important was thedetection of significantly (P < 0.001, Mann-Whitney U-test)increased hGBP-1 concentrations in the cerebrospinal fluid ofpatients with bacterial meningitis (n = 32) as compared to controlpatients (n = 74). In this first report of a secreted GTPase,we demonstrate that secreted hGBP-1 may be a useful surrogatemarker for diagnosis of bacterial meningitis.