{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:35:34Z","timestamp":1793500534188,"version":"4.5.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T00:00:00Z","timestamp":1395100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Cryptococcosis is caused by either\n Cryptococcus neoformans<\/jats:named-content>\n or\n C. gattii<\/jats:named-content>\n . While cryptococcal meningoencephalitis is caused mostly by\n C. neoformans<\/jats:named-content>\n in immunocompromised patients, the risk factors remain unclear for patients with no known immune defect. Recently, anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies were detected in the plasma of seven \u201cimmunocompetent\u201d cryptococcosis patients, and the cryptococcal strains from these patients were reported as\n C. neoformans<\/jats:named-content>\n (three strains),\n C. gattii<\/jats:named-content>\n (one strain), and\n Cryptococcus<\/jats:italic>\n (three strains not identified to the species level). We identified all three strains that had not been identified to the species level as\n C. gattii<\/jats:named-content>\n . Notably, the three strains that were reported as\n C. neoformans<\/jats:named-content>\n but were unavailable for species confirmation originated from Sothern California and Thailand where\n C. gattii<\/jats:named-content>\n is endemic. Most clinical laboratories designate\n C. neoformans<\/jats:named-content>\n without distinguishing between the two species; hence, these three strains could have been\n C. gattii<\/jats:named-content>\n . Since\n C. gattii<\/jats:named-content>\n infects more immunocompetent patients than\n C. neoformans<\/jats:named-content>\n , we pursued the possibility that this antibody may be more prevalent in patients infected with\n C. gattii<\/jats:named-content>\n than in those infected with\n C. neoformans<\/jats:named-content>\n . We screened the plasma of 20 healthy controls and 30 \u201cimmunocompetent\u201d patients with cryptococcal meningoencephalitis from China and Australia (multiple ethnicities). Anti-GM-CSF autoantibodies were detected only in the plasma of seven patients infected by\n C. gattii<\/jats:named-content>\n and one healthy volunteer and in none infected by\n C. neoformans<\/jats:named-content>\n . While plasma from these\n C. gattii<\/jats:named-content>\n patients completely prevented GM-CSF-induced p-STAT5 in normal human peripheral blood mononuclear cells (PBMCs), plasma from one healthy volunteer positive for anti-GM-CSF autoantibodies caused only partial blockage. Our results suggest that anti-GM-CSF autoantibodies may predispose otherwise immunocompetent individuals to meningoencephalitis caused by\n C. gattii<\/jats:named-content>\n but not necessarily to that caused by\n C. neoformans<\/jats:named-content>\n .\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n Cryptococcal meningoencephalitis is the most serious central nervous system (CNS) infection caused by\n Cryptococcus neoformans<\/jats:named-content>\n or\n C. gattii<\/jats:named-content>\n .\n Cryptococcus<\/jats:italic>\n primarily infects immunocopromised patients but is also sporadically encountered in otherwise \u201cimmunocompetent\u201d patients with no known risk. In a recent study, anti-GM-CSF autoantibodies were detected in the plasma of seven otherwise immunocompetent patients with cryptococcal meningoencephalitis. Four of seven (57%) cryptococcal isolates from these patients were identified as\n C. gattii<\/jats:named-content>\n , while three strains were unavailable for species confirmation. We collected plasma from 30 otherwise healthy patients with CNS cryptococcosis in China and Australia (multiethnic) and analyzed the samples for the presence of anti-GM-CSF autoantibodies. The results suggest that anti-GM-CSF autoantibodies are a risk factor for CNS infection by\n C. gattii<\/jats:named-content>\n but not\n C. neoformans<\/jats:named-content>\n . GM-CSF may have a specific role in host defense against\n C. gattii<\/jats:named-content>\n , thereby elevating the importance of determining the level of anti-GM-CSF autoantibodies which can impact clinical management.\n <\/jats:p>","DOI":"10.1128\/mbio.00912-14","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T21:33:29Z","timestamp":1395178409000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":208,"title":["Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies Are a Risk Factor for Central Nervous System Infection by Cryptococcus gattii in Otherwise Immunocompetent Patients"],"prefix":"10.1128","volume":"5","author":[{"given":"Tomomi","family":"Saijo","sequence":"first","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Key Laboratory of Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon C.-A.","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, New South Wales, Australia"},{"name":"Marie Bashir Institute, University of Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey B.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Key Laboratory of Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania C.","family":"Sorrell","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, New South Wales, Australia"},{"name":"Marie Bashir Institute, University of Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Holland","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Browne","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung J.","family":"Kwon-Chung","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"44","volume-title":"Medical mycology","author":"Kwon-Chung KJ","year":"1992","unstructured":"Kwon-ChungKJ BennettJE . 1992. 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