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Cerebrospinal Fluid Mononuclear Cell Phenotype and Activation Predictors of 2-Week and 1-Year Survival Among Persons
Morris K Rutakingirwa1,2, Kenneth Ssebambulidde2, Samuel Okurut2
1Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
Background:
Despite efforts to optimize therapy for HIV-associated cryptococcal meningitis (CM), survival outcomes remain poor. It is unclear how the cerebrospinal fluid (CSF) cellular immune phenotype and activation contribute to 2-week and 1-year survival following CM.
Methods:
We compared baseline CSF mononuclear cell phenotype and activation among adults with HIV-associated CM who died within 2 weeks of CM diagnosis to survivors who were alive at 1 year. The activated CSF T lymphocytes, CD14+ monocytes, and CD56+ natural killer cells were determined from freshly collected CSF using Cytek Aurora Spectroflo cytometry. Quantitative CSF soluble cryptococcal antigen (CrAg) titer from frozen CSF at baseline and 1 year was determined using CrAg lateral flow assay. Data were analyzed using STATA version 9.
Results:
Compared to survivors, participants who died within 2 weeks had significantly lower absolute CSF CD8+ T cells at baseline. For every 10% increase in PD-1 expression at baseline, the relative risk of 2-week mortality increased by 20%-60%. CSF CD14+ monocytes among those who died demonstrated low HLA-DR+ and high CD163+ expression compared to survivors. We noted a significant reduction in the median CSF CrAg titer from 1:2560 at baseline to 1:5 at 1 year (P < .0001) with 8 of 21 (38%) participants testing negative for CSF CrAg.
Conclusions:
Expression of CD163 on CD14+ macrophages and immune exhaustion of CSF mononuclear cells at baseline are associated with an increased risk of early mortality in CM. After 1 year of treatment, approximately 4 in 10 patients with CM have a negative CSF CrAg.
Insights
Immune cell exhaustion and CD163 expression in cerebrospinal fluid predict early mortality in HIV-associated cryptococcal meningitis (CM). This finding aids in understanding CM survival outcomes.
Area of Science:
- Immunology
- Infectious Diseases
- Neuroscience
Background:
- HIV-associated cryptococcal meningitis (CM) has poor survival outcomes despite therapeutic optimization.
- The role of cerebrospinal fluid (CSF) cellular immune phenotype and activation in CM survival remains unclear.
Purpose of the Study:
- To investigate the association between baseline CSF cellular immune phenotype and activation with 2-week and 1-year survival in HIV-associated CM.
Main Methods:
- Compared baseline CSF mononuclear cell phenotype and activation between early mortality and 1-year survival groups.
- Utilized Cytek Aurora Spectroflo cytometry for T-lymphocytes, CD14+monocytes, and CD56+natural killer cells.
- Quantified CSF cryptococcal antigen (CrAg) titer using lateral flow assay.
Main Results:
- Lower absolute CSF CD8+T cells and higher PD-1 expression were linked to 2-week mortality.
- Died participants showed low HLA-DR+ and high CD163+ expression on CSF CD14+ monocytes.
- CSF CrAg titer significantly decreased from baseline to 1-year, with 38% testing negative.
Conclusions:
- Baseline CSF CD14+ macrophage CD163 expression and immune exhaustion correlate with increased early mortality risk in CM.
- Approximately 40% of CM patients achieve a negative CSF CrAg after one year of treatment.
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