Utility of Cerebrospinal Fluid Protein Levels as a Potential Predictive Biomarker of Disease Severity in HIV-Associated Cryptococcal Meningitis
Background: Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis from being normal to markedly elevated. However, the clinical implications of CSF protein levels in cryptococcal meningitis remain unclear.
Methods: We analysed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into ≥100 mg/dL (n=249) and <100 mg/dL (n=641). We described baseline clinical variables and mortality by CSF protein levels.
Results: Approximately one-third of individuals had a baseline CSF protein ≥100 mg/dL. Those with CSF protein ≥100 mg/dL were more likely to present with Glasgow coma scale scores <15 (P<0.01), self-reported seizures at baseline (P=0.02), higher CD4 T-cells (p<0.001), and higher CSF white cells (p<0.001). Moreover, those with a baseline CSF protein ≥100 mg/dL also had a lower baseline CSF fungal burden (p<0.001) and a higher percentage of sterile CSF cultures at day 14 (p=0.02). Individuals with CSF protein ≥100 mg/dL demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules pro-inflammatory cytokines, type-1 T-helper cell cytokines, type-3 chemokines, and immune-exhaustion marker (p<0.05). 18-week mortality risk in individuals with a CSF protein <100 mg/dL was 34% higher, (unadjusted Hazard Ratio 1.34; 95% CI, 1.05 to 1.70; p=0.02) than those with ≥100 mg/dL.
Conclusion: In cryptococcal meningitis, individuals with CSF protein ≥100 mg/dL more frequently presented with seizures, altered mental status, immune activation, and favourable fungal outcomes. Baseline CSF protein levels may serve as a surrogate marker of immune activation and prognosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
medRxiv : the preprint server for health sciences - (2023) vom: 11. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kasibante, John [VerfasserIn] |
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| Links: |
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| Themen: |
CSF cytokines |
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| Anmerkungen: |
Date Revised 27.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2023.12.10.23299793 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366589946 |
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| 100 | 1 | |a Kasibante, John |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Utility of Cerebrospinal Fluid Protein Levels as a Potential Predictive Biomarker of Disease Severity in HIV-Associated Cryptococcal Meningitis |
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| 500 | |a Date Revised 27.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Background: Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis from being normal to markedly elevated. However, the clinical implications of CSF protein levels in cryptococcal meningitis remain unclear | ||
| 520 | |a Methods: We analysed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into ≥100 mg/dL (n=249) and <100 mg/dL (n=641). We described baseline clinical variables and mortality by CSF protein levels | ||
| 520 | |a Results: Approximately one-third of individuals had a baseline CSF protein ≥100 mg/dL. Those with CSF protein ≥100 mg/dL were more likely to present with Glasgow coma scale scores <15 (P<0.01), self-reported seizures at baseline (P=0.02), higher CD4 T-cells (p<0.001), and higher CSF white cells (p<0.001). Moreover, those with a baseline CSF protein ≥100 mg/dL also had a lower baseline CSF fungal burden (p<0.001) and a higher percentage of sterile CSF cultures at day 14 (p=0.02). Individuals with CSF protein ≥100 mg/dL demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules pro-inflammatory cytokines, type-1 T-helper cell cytokines, type-3 chemokines, and immune-exhaustion marker (p<0.05). 18-week mortality risk in individuals with a CSF protein <100 mg/dL was 34% higher, (unadjusted Hazard Ratio 1.34; 95% CI, 1.05 to 1.70; p=0.02) than those with ≥100 mg/dL | ||
| 520 | |a Conclusion: In cryptococcal meningitis, individuals with CSF protein ≥100 mg/dL more frequently presented with seizures, altered mental status, immune activation, and favourable fungal outcomes. Baseline CSF protein levels may serve as a surrogate marker of immune activation and prognosis | ||
| 650 | 4 | |a Preprint | |
| 650 | 4 | |a CSF cytokines | |
| 650 | 4 | |a CSF protein | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a cerebral spinal fluid | |
| 650 | 4 | |a cryptococcal meningitis | |
| 650 | 4 | |a predictive biomarker | |
| 700 | 1 | |a Irfanullah, Eesha |e verfasserin |4 aut | |
| 700 | 1 | |a Wele, Abduljewad |e verfasserin |4 aut | |
| 700 | 1 | |a Okafor, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Ssebambulidde, Kenneth |e verfasserin |4 aut | |
| 700 | 1 | |a Okurut, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Kagimu, Enock |e verfasserin |4 aut | |
| 700 | 1 | |a Gakuru, Jane |e verfasserin |4 aut | |
| 700 | 1 | |a Rutakingirwa, Morris K |e verfasserin |4 aut | |
| 700 | 1 | |a Mugabi, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Nuwagira, Edwin |e verfasserin |4 aut | |
| 700 | 1 | |a Jjunju, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Mpoza, Edward |e verfasserin |4 aut | |
| 700 | 1 | |a Tugume, Lillian |e verfasserin |4 aut | |
| 700 | 1 | |a Nsangi, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Musibire, Abdu K |e verfasserin |4 aut | |
| 700 | 1 | |a Muzoora, Conrad |e verfasserin |4 aut | |
| 700 | 1 | |a Rhein, Joshua |e verfasserin |4 aut | |
| 700 | 1 | |a Meya, David B |e verfasserin |4 aut | |
| 700 | 1 | |a Boulware, David R |e verfasserin |4 aut | |
| 700 | 1 | |a Abassi, Mahsa |e verfasserin |4 aut | |
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