Abstract
BackgroundCryptococcal Meningitis (CM) is a common opportunistic infection in the late stage of acquired immunodeficiency syndrome (AIDS). Despite the wide use of effective antiretroviral and antifungal therapy in AIDS patients, CM is still a major morbidity and mortality cause. Understanding the immune response in cryptococcal infection may help to improve the treatment strategies.MethodsWe established a prospective cohort of twelve AIDS patients with CM (HIV + CM+) admitted to the hospital from 2019 to 2020. All patients were examined at the baseline, 2 weeks, and 4 weeks thereafter. The level of 19 cytokines in cerebrospinal fluid (CSF) were recorded to analyze the characteristics and dynamic changes of Th1/Th2 immune response. Meanwhile, six AIDS patients without CM (HIV + CM-) and seventeen healthy subjects (HIV-CM-) were included as control groups for CSF assessment.ResultsThe HIV+ CM+ group had higher CSF IFN-γ, TNF-α, IL-6, IL-7, IL-8, IL-10, IL-12 (P40), IL-15, IL-18, CCL2 levels but lower IL-4 when compared with the HIV-CM- group at baseline. And they also had a higher level of IL-12 (P40) and IL-17A compared with HIV + CM- patients. Except one patient dropped out of the study, eleven HIV + CM+ patients received induction antifungal therapy and regular CSF testing, and the mortality rate was 9.1% (1/11) and 18.2% (2/11) respectively at week 2 and week 4. Compared with baseline CSF cytokines, IL-2, IL-13, IL-17A, and VEGF-A decreased in week 2, and the VEGF-A levels further decreased in week 4. But there was no difference in the levels of all cytokines between survivors and the dead.ConclusionNo evidence of Th1/Th2 imbalance was found in AIDS patients with CM. However, the CSF cytokine network may provide new clues for the treatment of AIDS patients with CM.Trial registrationThis trial was prospectively registered in 2019.7.16. The registered number is ChiCTR1900024565.
Highlights
Cryptococcal Meningitis (CM) is a common opportunistic infection in the late stage of acquired immunodeficiency syndrome (AIDS)
A study indicated that high serum pre-antiretroviral therapy (ART) levels of IL-4 and IL-17 were predictive of future immune reconstitution inflammatory syndrome (IRIS) in AIDS patients with CM [17]
We found in Human immunodeficiency virus (HIV)+ CM+ group the higher cerebrospinal fluid (CSF) IFN-γ, Tumor Necrosis Factor-α (TNF-α), IL-6, IL7, IL-8, IL-10, IL-12 (P40), IL-15, IL-18, CCL2 levels but lower IL-4 when compared with the Non-AIDS and non-CM patients (HIV-CM)- group, while a higher level of IL-12 (P40) and IL-17A compared with HIV + CM- group
Summary
Cryptococcal Meningitis (CM) is a common opportunistic infection in the late stage of acquired immunodeficiency syndrome (AIDS). Understanding the immune response in cryptococcal infection may help to improve the treatment strategies. Cryptococcal meningitis (CM) is a common opportunistic infection in the late stage of acquired immunodeficiency syndrome (AIDS), which causes the second most AIDS-related death after tuberculosis [1, 2]. CM has been effectively controlled with the widespread application of antiretroviral therapy (ART) and antifungal drugs, the mortality rate of CM in AIDS patients remains high ranging from 30 to 50%, especially for patients in low-resource settings [3, 4]. A study indicated that high serum pre-ART levels of IL-4 and IL-17 were predictive of future immune reconstitution inflammatory syndrome (IRIS) in AIDS patients with CM [17]
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