Human Immune Response Varies by the Degree of Relative Cryptococcal Antigen Shedding

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dc.contributor.authorBoulware, David R.
dc.contributor.authorHohenberg, Maximilian von
dc.contributor.authorRhein, Joshua
dc.contributor.authorAkampurira, Andrew
dc.contributor.authorWilliams, Darlisha A.
dc.contributor.authorTaseera, Kabanda
dc.contributor.authorMcDonald, Tami
dc.contributor.authorMuzoora, Conrad
dc.contributor.authorMeya, David B.
dc.contributor.authorHullsiek, Katherine Huppler
dc.contributor.authorFor the Cryptococcal Optimal ART Timing (COAT) Trial Team
dc.date.accessioned2022-08-19T13:22:48Z
dc.date.available2022-08-19T13:22:48Z
dc.date.issued2016
dc.description.abstractCerebrospinal fluid (CSF) cryptococcal glucuronoxylomannan antigen (CrAg) titers generally correlate with quantitative fungal culture burden; however, correlation is not precise. Some patients have higher CrAg titers with lower fungal burdens and vice versa. We hypothesized that the relative discordancy between CrAg titer and quantitative culture burden reflects the relative degree of CrAg shedding by Cryptococcus neoformans and is associated with human immune responses.One hundred ninety human immunodeficiency virus-infected individuals with cryptococcal meningitis were enrolled in Uganda and South Africa. We compared initial CSF CrAg titers relative to their CSF quantitative cultures to determine low (n = 58), intermediate (n = 68), or high (n = 64) CrAg shedders. We compared cytokines measured by Luminex multiplex assay on cryopreserved CSF and 10-week mortality across shedding groups using linear and logistic regression and distribution of genotypes by multilocus sequence typing.The relative degree of CrAg shedding was positively associated with increasing CSF levels of the following: interleukin (IL)-6, IL-7, IL-8, and tumor necrosis factor-α (each P < 0.01), which are all secreted by antigen-presenting cells and negatively associated with vascular endothelial growth factor (P = .01). In addition, IL-5, IL-13, granulocyte colony-stimulating factor, and macrophage chemotactic protein were decreased in low-CrAg shedders compared with intermediate shedders (each P ≤ .01). Type 1 T-helper cells (Th1) cytokine responses and 10-week mortality did not differ between the shedding groups. Cryptococcal genotypes were equally distributed across shedding groups.Discordancy between CrAg shedding and expected shedding based on quantitative fungal burden is associated with detectable immunologic differences in CSF, primarily among secreted cytokines and chemokines produced by antigen-presenting cells and Th2.en_US
dc.identifier.citationBoulware, D. R., von Hohenberg, M., Rolfes, M. A., Bahr, N. C., Rhein, J., Akampurira, A., ... & Butler, E. K. (2016, January). Human immune response varies by the degree of relative cryptococcal antigen shedding. In Open forum infectious diseases (Vol. 3, No. 1). Oxford University Press.https://doi.org/10.1093/ofid/ofv194en_US
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/4320
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.subjectcerebrospinal fluid, cryptococcal meningitis, Cryptococcus, HIV/AIDS, immune responseen_US
dc.titleHuman Immune Response Varies by the Degree of Relative Cryptococcal Antigen Sheddingen_US
dc.typeArticleen_US
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