{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:05:42Z","timestamp":1792033542292,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571968"],"award-info":[{"award-number":["81571968"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971911"],"award-info":[{"award-number":["81971911"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cryptococcal meningitis (CM)\u2010associated immune reconstitution inflammatory syndrome (IRIS) is associated with high mortality, the epidemiology and pathophysiology of which is poorly understood, especially in non\u2010HIV populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We aim to explore the incidence, clinical risk factors, immunological profiles and potential influence of leukotriene A4 hydroxylase (<jats:italic>LTA4H<\/jats:italic>) on non\u2010HIV CM IRIS populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this observational cohort study, 101 previously untreated non\u2010HIV CM patients were included. We obtained data for clinical variables, 27 cerebrospinal fluid (CSF) cytokines levels and <jats:italic>LTA4H<\/jats:italic> genotype frequencies. Changes of CSF cytokines levels before and at IRIS occurrence were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immune reconstitution inflammatory syndrome was identified in 11 immunocompetent males, generating an incidence of 10.9% in non\u2010HIV CM patients. Patients with higher CrAg titres (&gt; 1:160) were more likely to develop IRIS, and titre of 1:1280 is the optimum level to predict IRIS occurrence. Baseline CSF cytokines were significantly higher in IRIS group, which indicated a severe host immune inflammation response. Four <jats:italic>LTA4H<\/jats:italic> SNPs (rs17525488, rs6538697, rs17525495 and rs1978331) exhibited significant genetic susceptibility to IRIS in overall non\u2010HIV CM, while five cytokines were found to be associated with rs1978331, and baseline monocyte chemotactic protein 1 (MCP\u20101) became the only cytokine correlated with both IRIS and <jats:italic>LTA4H<\/jats:italic> SNPs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study suggested that non\u2010HIV CM patients with high fungal burden and severe immune inflammation response were more likely to developed IRIS. <jats:italic>LTA4H<\/jats:italic> polymorphisms may affect the pathogenesis of IRIS by regulating the level of baseline CSF MCP\u20101.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13361","type":"journal-article","created":{"date-parts":[[2021,8,14]],"date-time":"2021-08-14T08:16:04Z","timestamp":1628928964000},"page":"1402-1411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Immune reconstitution inflammatory syndrome in non\u2010HIV cryptococcal meningitis: Cross\u2010talk between pathogen and host"],"prefix":"10.1111","volume":"64","author":[{"given":"Ling\u2010Hong","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Huashan Hospital Shanghai Medical college Fudan University Shanghai China"},{"name":"Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua\u2010Zhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Infectious 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