Publications & Reports

Chemokine levels and chemokine receptor expression in blood and the CSF of HIV-infected patients with cryptococcal meningitis and C-IRIS.

Chang CC, Omarjee S, Lim A, Spelman T, Gosnell BI, Carr WH, Elliott JH, Moosa MY, Ndung'u T, French MA, Lewin SR
Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne 3000, Australia.

Abstract

Background. HIV-infected patients with treated cryptococcal meningitis (CM) who initiate combination antiretroviral therapy (cART) are at risk of further neurological deterioration (ND), 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 Th1 T-cells and/or myeloid cells to the central nervous system (CNS).Methods. In a prospective study of 128 HIV-infected patients with CM 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 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 concentration of CXCL10, CCL2 and CCL3 were increased in CSF compared to blood at cART initiation (p<0.0001). C-IRIS patients (n=26), compared to patients with no-ND (n=63), had higher CSF ratios of CCL2/CXCL10 and CCL3/CXCL10; and higher proportions of CXCR3+CCR5+CD8+T-cells in CSF compared to blood at cART initiation (p=0.0250, 0.053, 0.0177 respectively).Conclusion. CD8+ T-cell and myeloid cell trafficking to the CNS may predispose to C-IRIS.

Publication

  • Journal: The Journal of Infectious Diseases
  • Published: 01/08/2013
  • Volume: 208
  • Issue: 10
  • Pagination: 1604-1612

Authors

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