Chemokine levels and chemokine receptor expression in the blood and the cerebrospinal fluid of HIV-infected patients with cryptococcal meningitis and cryptococcosis- Associated immune reconstitution inflammatory syndrome

C.C. Chang, S. Omarjee, Andrew Lim, T. Spelman, B.I. Gosnell, W.H. Carr, J.H. Elliott, M.Y.S. Moosa, T. Ndung'U, Martyn French, S.R. Lewin

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    Abstract

    Background. Human immunodeficiency virus-infected patients with treated cryptococcal meningitis who start combination antiretroviral therapy (cART) are at risk of further neurological deterioration, in part caused by paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). We hypothesized that C-IRIS is associated with alterations of chemokine receptor expression on T cells and chemokine concentrations in cerebrospinal fluid (CSF) that enhance recruitment of T-helper 1 cells and/or myeloid cells to the central nervous system. Methods. In a prospective study of 128 human immunodeficiency virus-infected patients with cryptococcal meningitis who received antifungal therapy followed by cART, we examined the proportions of CD4+ and CD8+ T cells expressing CCR5 and/or CXCR3, in CSF and whole blood and the concentrations of CXCL10, CCL2, and CCL3 in stored CSF and plasma. Results. The proportion of CD4+ and CD8+ T cells expressing CXCR3+CCR5+ and the concentrations of CXCL10, CCL2 and CCL3 were increased in CSF compared with blood at cART initiation (P <.0001). Patients with C-IRIS (n = 26), compared with those with no neurological deterioration (n = 63), had higher CSF ratios of CCL2/CXCL10 and CCL3/CXCL10 and higher proportions of CXCR3+CCR5+CD8+T cells in CSF compared with blood at cART initiation (P = .03, .0053, and .02, respectively). Conclusion. CD8+ T-cell and myeloid cell trafficking to the central nervous system may predispose patients to C-IRIS. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
    Original languageEnglish
    Pages (from-to)1604-1612
    JournalJournal of Infectious Diseases
    Volume208
    Issue number10
    DOIs
    Publication statusPublished - 2013

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