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).
  
  
  CONCLUSIONS
  CD8(+) T-cell and myeloid cell trafficking to the central nervous system may predispose patients to C-IRIS.
authors.affiliation: Department of Infectious Diseases, Alfred Hospital.
authors.forename: Christina C
authors.initials: CC
authors.lastname: Chang
authors.forename: Saleha
authors.initials: S
authors.lastname: Omarjee
authors.forename: Andrew
authors.initials: A
authors.lastname: Lim
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.forename: Bernadett I
authors.initials: BI
authors.lastname: Gosnell
authors.forename: William H
authors.initials: WH
authors.lastname: Carr
authors.forename: Julian H
authors.initials: JH
authors.lastname: Elliott
authors.forename: Mohamed-Yunus S
authors.initials: MY
authors.lastname: Moosa
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D008297:Male; D016919:Meningitis, Cryptococcal / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D011446:Prospective Studies; D019707:Receptors, Chemokine / Q000097:blood / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D018925:Chemokines; D019707:Receptors, Chemokine
keywords: HIV; chemokines; cryptococcus; immune restoration disease
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