PMID- 34390048 OWN - NLM STAT- MEDLINE DCOM- 20211104 LR - 20220731 IS - 1439-0507 (Electronic) IS - 0933-7407 (Print) IS - 0933-7407 (Linking) VI - 64 IP - 11 DP - 2021 Nov TI - Immune reconstitution inflammatory syndrome in non-HIV cryptococcal meningitis: Cross-talk between pathogen and host. PG - 1402-1411 LID - 10.1111/myc.13361 [doi] AB - BACKGROUND: Cryptococcal meningitis (CM)-associated immune reconstitution inflammatory syndrome (IRIS) is associated with high mortality, the epidemiology and pathophysiology of which is poorly understood, especially in non-HIV populations. OBJECTIVES: We aim to explore the incidence, clinical risk factors, immunological profiles and potential influence of leukotriene A4 hydroxylase (LTA4H) on non-HIV CM IRIS populations. METHODS: In this observational cohort study, 101 previously untreated non-HIV CM patients were included. We obtained data for clinical variables, 27 cerebrospinal fluid (CSF) cytokines levels and LTA4H genotype frequencies. Changes of CSF cytokines levels before and at IRIS occurrence were compared. RESULTS: Immune reconstitution inflammatory syndrome was identified in 11 immunocompetent males, generating an incidence of 10.9% in non-HIV CM patients. Patients with higher CrAg titres (> 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 LTA4H SNPs (rs17525488, rs6538697, rs17525495 and rs1978331) exhibited significant genetic susceptibility to IRIS in overall non-HIV CM, while five cytokines were found to be associated with rs1978331, and baseline monocyte chemotactic protein 1 (MCP-1) became the only cytokine correlated with both IRIS and LTA4H SNPs. CONCLUSIONS: Our study suggested that non-HIV CM patients with high fungal burden and severe immune inflammation response were more likely to developed IRIS. LTA4H polymorphisms may affect the pathogenesis of IRIS by regulating the level of baseline CSF MCP-1. CI - (c) 2021 The Authors. Mycoses published by Wiley-VCH GmbH. FAU - Zhou, Ling-Hong AU - Zhou LH AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. FAU - Zhao, Hua-Zhen AU - Zhao HZ AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. FAU - Wang, Xuan AU - Wang X AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. FAU - Wang, Rui-Ying AU - Wang RY AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. FAU - Jiang, Ying-Kui AU - Jiang YK AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. FAU - Huang, Li-Ping AU - Huang LP AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. FAU - Yip, Ching-Wan AU - Yip CW AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. FAU - Cheng, Jia-Hui AU - Cheng JH AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. FAU - Que, Chun-Xing AU - Que CX AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. FAU - Zhu, Li-Ping AU - Zhu LP AUID- ORCID: 0000-0002-3098-7307 AD - Department of Infectious Diseases, Huashan Hospital, Shanghai Medical college, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. LA - eng GR - 81571968/National Natural Science Foundation of China/ GR - 81971911/National Natural Science Foundation of China/ PT - Journal Article PT - Observational Study DEP - 20210819 PL - Germany TA - Mycoses JT - Mycoses JID - 8805008 RN - 0 (Cytokines) RN - EC 3.3.2.- (Epoxide Hydrolases) RN - V38765PUZ6 (leukotriene A4 hydrolase) SB - IM MH - Adult MH - Cohort Studies MH - Cytokines/cerebrospinal fluid MH - Epoxide Hydrolases/*genetics MH - Female MH - Gene Frequency MH - Genotype MH - Humans MH - Immune Reconstitution Inflammatory Syndrome/*complications/*epidemiology/immunology MH - Immunocompetence MH - Incidence MH - Male MH - Meningitis, Cryptococcal/*complications MH - Middle Aged MH - Multivariate Analysis MH - Polymorphism, Single Nucleotide MH - Risk Factors PMC - PMC9290805 OTO - NOTNLM OT - LTA4H OT - chemokines OT - cryptococcal meningitis OT - immune reconstitution inflammatory syndrome OT - non-HIV patients COIS- The authors declare no conflict of interest. EDAT- 2021/08/15 06:00 MHDA- 2021/11/05 06:00 PMCR- 2022/07/18 CRDT- 2021/08/14 06:31 PHST- 2021/08/06 00:00 [revised] PHST- 2021/03/31 00:00 [received] PHST- 2021/08/07 00:00 [accepted] PHST- 2021/08/15 06:00 [pubmed] PHST- 2021/11/05 06:00 [medline] PHST- 2021/08/14 06:31 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - MYC13361 [pii] AID - 10.1111/myc.13361 [doi] PST - ppublish SO - Mycoses. 2021 Nov;64(11):1402-1411. doi: 10.1111/myc.13361. Epub 2021 Aug 19.