Immune reconstitution inflammatory syndrome in non-HIV cryptococcal meningitis: Cross-talk between pathogen and host.
Adult
Cohort Studies
Cytokines
/ cerebrospinal fluid
Epoxide Hydrolases
/ genetics
Female
Gene Frequency
Genotype
Humans
Immune Reconstitution Inflammatory Syndrome
/ complications
Immunocompetence
Incidence
Male
Meningitis, Cryptococcal
/ complications
Middle Aged
Multivariate Analysis
Polymorphism, Single Nucleotide
Risk Factors
LTA4H
chemokines
cryptococcal meningitis
immune reconstitution inflammatory syndrome
non-HIV patients
Journal
Mycoses
ISSN: 1439-0507
Titre abrégé: Mycoses
Pays: Germany
ID NLM: 8805008
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
revised:
06
08
2021
received:
31
03
2021
accepted:
07
08
2021
pubmed:
15
8
2021
medline:
5
11
2021
entrez:
14
8
2021
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
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
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
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
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.
Identifiants
pubmed: 34390048
doi: 10.1111/myc.13361
pmc: PMC9290805
doi:
Substances chimiques
Cytokines
0
Epoxide Hydrolases
EC 3.3.2.-
leukotriene A4 hydrolase
V38765PUZ6
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1402-1411Subventions
Organisme : National Natural Science Foundation of China
ID : 81571968
Organisme : National Natural Science Foundation of China
ID : 81971911
Informations de copyright
© 2021 The Authors. Mycoses published by Wiley-VCH GmbH.
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