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

Open Forum Infectious Diseases
David R BoulwareKatherine Huppler Hullsiek

Abstract

Background.  Cerebrospinal 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. Methods.  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. Results.  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 ant...Continue Reading

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Citations

Aug 16, 2016·Case Reports in Neurological Medicine·Kedar R MahajanLori Sheehan
Oct 28, 2016·Nature Reviews. Neurology·Lauren N BowenAvindra Nath
Jul 25, 2018·Open Forum Infectious Diseases·Irina Vlasova-St LouisPaul R Bohjanen
May 22, 2021·Infectious Disease Clinics of North America·Alexis C GushikenJohn W Baddley
Jul 7, 2021·Medical Microbiology and Immunology·Aline Beatriz Mahler PereiraAlexandre Paula Rogerio

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