{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:39:19Z","timestamp":1787942359316,"version":"build-2784847793"},"reference-count":58,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"am","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>We describe the immunophenotyping and genetic analysis of human immunodeficiency virus (HIV)-uninfected apparently immunocompetent adults presenting with disseminated cryptococcosis. Cryptococci are environmentally ubiquitous fungi that may cause disseminated infection, including meningitis. Cryptococcosis occurs predominantly in immunocompromised hosts and most commonly in the context of HIV infection. In apparently immunocompetent patients, cryptococcal disease is rare, often diagnosed later and associated with higher mortality. The immunologic work-up and management of this patient group are challenging and poorly studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Between 2015 and 2021, eight apparently immunocompetent adults at the time of diagnosis with cryptococcosis underwent extensive diagnostic immunological work-up, including T-\/B-cell subsets, immunoglobulins, T-cell proliferation and phenotyping, serum-specific antibody responses, mannose binding lectin, measurement of selected cytokines, anti-cytokine autoantibodies and targeted genetic next-generation sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The production of interleukin (IL)-17 following phytohaemagglutinin (PHA) stimulation was significantly reduced in all eight patients with cryptococcosis compared to healthy controls (median IL-17 concentration in whole blood stimulation assay 88.1pg\/mL in patients; 452.1pg\/mL in controls, P\u2005=\u20050.0047). In 5\/5 patients tested, the percentage of CD4+ T-cells positive for IL-17, including memory CD4+CD45RO+ IL-17+ T cells, after stimulation with staphylococcal enterotoxin B (SEB) was significantly reduced (\u22640.4% cells). Reduced IgM+ memory B cells were noted in 4\/5 tested. 4\/8 patients were found to have CD4 lymphopaenia. One patient with Cryptococcus gattii infection had autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). No underlying genetic causes were identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients had several immunological risk factors, but reduced IL-17 production was a striking feature across the cohort\u2014a phenotype that may facilitate tailored immunotherapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cei\/uxaf053","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T11:52:44Z","timestamp":1755777164000},"source":"Crossref","is-referenced-by-count":4,"title":["Immunophenotyping of apparently immunocompetent hosts with cryptococcosis reveals IL-17 deficiency as a unifying susceptibility factor"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2754-2363","authenticated-orcid":false,"given":"Katie","family":"Townsend","sequence":"first","affiliation":[{"name":"Institute of 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,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Ceron-Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Immunology, Addenbrooke\u2019s Hospital , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya","family":"Ebrahimi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Immunology, Addenbrooke\u2019s Hospital , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlada","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Immunology, Addenbrooke\u2019s Hospital , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Gothard","sequence":"additional","affiliation":[{"name":"Hospital for Tropical Diseases, Division of Infection, University College London Hospitals NHS Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brown","sequence":"additional","affiliation":[{"name":"Hospital for Tropical Diseases, Division of Infection, University College London Hospitals NHS Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariba","family":"Tahami","sequence":"additional","affiliation":[{"name":"Department of Immunology, Great Ormond Street Hospital NHS Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dakshika","family":"Jayaratnam","sequence":"additional","affiliation":[{"name":"HCAI, Fungal, AMR, AMU & Sepsis Division, UK Health Security Agency , London ,","place":["UK"]},{"name":"Department of Infectious Diseases, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna L","family":"Goodman","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust , London ,","place":["UK"]},{"name":"Centre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, School of Immunology and Microbial Sciences, King\u2019s College London , London ,","place":["UK"]},{"name":"MRC Clinical Trials Unit, UCL , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Macallan","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, St George\u2019s, University of London , London ,","place":["UK"]},{"name":"Infection Clinical Academic Group, St George\u2019s University Hospitals NHS Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S","family":"Harrison","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, St George\u2019s, University of London , London ,","place":["UK"]},{"name":"Infection Clinical Academic Group, St George\u2019s University Hospitals NHS Foundation Trust , London ,","place":["UK"]},{"name":"MRC Centre for Medical Mycology, University of Exeter , Exeter ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4287-7893","authenticated-orcid":false,"given":"Magda","family":"Dziadzio","sequence":"additional","affiliation":[{"name":"Department of Specialist Allergy and Clinical Immunology, University College London Hospitals , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Lambourne","sequence":"additional","affiliation":[{"name":"Department of Infection, Barts Health NHS Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanaraj","family":"Perinpanathan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Northwick Park Hospital, London North West University Healthcare Trust , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"John","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Northwick Park Hospital, London North West University Healthcare Trust , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1210-6166","authenticated-orcid":false,"given":"Neil","family":"Stone","sequence":"additional","affiliation":[{"name":"Hospital for Tropical Diseases, Division of Infection, University College London Hospitals NHS Foundation Trust , London 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