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Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis.
Okurut, Samuel; Boulware, David R; Okafor, Elizabeth; Rhein, Joshua; Kajumbula, Henry; Bagaya, Bernard S; Bwanga, Freddie; Olobo, Joseph O; Manabe, Yukari C; Meya, David B; Janoff, Edward N.
Afiliación
  • Okurut S; Translation Sciences Laboratory, Research Department, Infectious Diseases Institute, Makerere University, Kampala, Uganda.
  • Boulware DR; Department of Medical Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
  • Okafor E; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
  • Rhein J; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
  • Kajumbula H; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
  • Bagaya BS; Department of Medical Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
  • Bwanga F; Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
  • Olobo JO; Department of Medical Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
  • Manabe YC; Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
  • Meya DB; Translation Sciences Laboratory, Research Department, Infectious Diseases Institute, Makerere University, Kampala, Uganda.
  • Janoff EN; Division of Infectious Diseases, Department of Medicine, John Hopkins University School of Medicine, Baltimore, MD, United States.
Front Immunol ; 14: 1275443, 2023.
Article en En | MEDLINE | ID: mdl-38152404
ABSTRACT

Introduction:

Survival among people with HIV-associated cryptococcal meningitis (CM) remains low, particularly among women, despite the currently optimal use of antifungal drugs. Cryptococcus dissemination into the central nervous system [brain, spinal cord, and cerebrospinal fluid (CSF)] elicits the local production of cytokines, chemokines, and other biomarkers. However, no consistent diagnostic or prognostic neuroimmune signature is reported to underpin the risk of death or to identify mechanisms to improve treatment and survival. We hypothesized that distinct neuroimmune signatures in the CSF would distinguish survivors from people who died on antifungal treatment and who may benefit from tailored therapy.

Methods:

We considered baseline clinical features, CSF cryptococcal fungal burden, and CSF neuroimmune signatures with survival at 18 weeks among 419 consenting adults by "gender" (168 women and 251 men by biological sex defined at birth).

Results:

Survival at 18 weeks was significantly lower among women than among men {47% vs. 59%, respectively; hazard ratio (HR) = 1.4 [95% confidence interval (CI), 1.0 to 1.9; p = 0.023]}. Unsupervised principal component analysis (PCA) demonstrated divergent neuroimmune signatures by gender, survival, and intragender-specific survival. Overall, women had lower levels of programmed death ligand 1, Interleukin (IL) (IL-11RA/IL-1F30, and IL-15 (IL-15) than men (all p < 0.028). Female survivors compared with those who died expressed significant elevations in levels of CCL11 and CXCL10 chemokines (both p = 0.001), as well as increased T helper 1, regulatory, and T helper 17 cytokines (all p < 0.041). In contrast, male survivors expressed lower levels of IL-15 and IL-8 compared with men who died (p < 0.044).

Conclusions:

Survivors of both genders demonstrated a significant increase in the levels of immune regulatory IL-10. In conclusion, the lower survival among women with CM was accompanied by distinct differential gender-specific neuroimmune signatures. These female and male intragender-specific survival-associated neuroimmune signatures provide potential targets for interventions to advance therapy to improve the low survival among people with HIV-associated CM.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Meningitis Criptocócica Límite: Adult / Female / Humans / Male / Newborn Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Uganda Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Meningitis Criptocócica Límite: Adult / Female / Humans / Male / Newborn Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Uganda Pais de publicación: Suiza