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

Christina Catherine Chang, Saleha Omarjee, Andrew Lim, Tim Spelman, Bernadett Gosnell, William H Carr, Julian Elliott, Mohamed-Yunus S Moosa, Thumbi Ndung'u, Martyn French, Sharon Ruth Lewin

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

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
Number of pages9
JournalJournal of Infectious Diseases
Volume208
Issue number10
DOIs
Publication statusPublished - 2013

Cite this

@article{bf6bb56062dd45a3a84d09a97be410c8,
title = "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",
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.",
author = "Chang, {Christina Catherine} and Saleha Omarjee and Andrew Lim and Tim Spelman and Bernadett Gosnell and Carr, {William H} and Julian Elliott and Moosa, {Mohamed-Yunus S} and Thumbi Ndung'u and Martyn French and Lewin, {Sharon Ruth}",
year = "2013",
doi = "10.1093/infdis/jit388",
language = "English",
volume = "208",
pages = "1604 -- 1612",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "10",

}

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. / Chang, Christina Catherine; Omarjee, Saleha; Lim, Andrew; Spelman, Tim; Gosnell, Bernadett; Carr, William H; Elliott, Julian; Moosa, Mohamed-Yunus S; Ndung'u, Thumbi; French, Martyn; Lewin, Sharon Ruth.

In: Journal of Infectious Diseases, Vol. 208, No. 10, 2013, p. 1604 - 1612.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 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

AU - Chang, Christina Catherine

AU - Omarjee, Saleha

AU - Lim, Andrew

AU - Spelman, Tim

AU - Gosnell, Bernadett

AU - Carr, William H

AU - Elliott, Julian

AU - Moosa, Mohamed-Yunus S

AU - Ndung'u, Thumbi

AU - French, Martyn

AU - Lewin, Sharon Ruth

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://jid.oxfordjournals.org/content/208/10/1604.full.pdf

U2 - 10.1093/infdis/jit388

DO - 10.1093/infdis/jit388

M3 - Article

VL - 208

SP - 1604

EP - 1612

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 10

ER -