Cryptococcosis-IRIS is associated with lower Cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy

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

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Abstract

Background. Cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) may be driven by aberrant T-cell responses against cryptococci. We investigated this in human immunodeficiency virus (HIV)?infected patients with treated cryptococcal meningitis (CM) commencing combination antiretroviral therapy (cART). Methods. Mitogen- and cryptococcal mannoprotein (CMP)?activated (CD25+CD134+) CD4+ T cells and -induced production of interferon-gamma (IFN-?), IL-10, and CXCL10 were assessed in whole blood cultures in a prospective study of 106 HIV?CM coinfected patients. Results. Patients with paradoxical C-IRIS (n = 27), compared with patients with no neurological deterioration (no ND; n = 63), had lower CMP-induced IFN-? production in 24-hour cultures pre-cART and 4 weeks post-cART (P = .0437 and .0257, respectively) and lower CMP-activated CD4+ T-cell counts pre-cART (P = .0178). Patients surviving to 24 weeks had higher proportions of mitogen-activated CD4+ T cells and higher CMP-induced CXCL10 and IL-10 production in 24-hour cultures pre-cART than patients not surviving (P = .0053, .0436 and .0319, respectively). C-IRIS was not associated with higher CMP-specific T-cell responses before or during cART. Conclusion. Greater preservation of T-cell function and higher CMP-induced IL-10 and CXCL10 production before cART are associated with improved survival while on cART. Lower CMP-induced IFN-? production pre-cART, but not higher CMP-specific T-cell responses after cART, were risk factors for C-IRIS.
Original languageEnglish
Pages (from-to)898 - 906
Number of pages9
JournalJournal of Infectious Diseases
Volume208
Issue number6
DOIs
Publication statusPublished - 2013

Cite this

Chang, Christina Catherine ; Lim, Andrew ; Omarjee, Saleha ; Levitz, Stuart M ; Gosnell, Bernadett ; Spelman, Tim Denis ; Elliott, Julian ; Carr, William H ; Moosa, Mohamed-Yunus S ; Ndung'u, Thumbi ; Lewin, Sharon Ruth ; French, Martyn. / Cryptococcosis-IRIS is associated with lower Cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy. In: Journal of Infectious Diseases. 2013 ; Vol. 208, No. 6. pp. 898 - 906.
@article{85f2c79c547e47ffb4445fda857241d3,
title = "Cryptococcosis-IRIS is associated with lower Cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy",
abstract = "Background. Cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) may be driven by aberrant T-cell responses against cryptococci. We investigated this in human immunodeficiency virus (HIV)?infected patients with treated cryptococcal meningitis (CM) commencing combination antiretroviral therapy (cART). Methods. Mitogen- and cryptococcal mannoprotein (CMP)?activated (CD25+CD134+) CD4+ T cells and -induced production of interferon-gamma (IFN-?), IL-10, and CXCL10 were assessed in whole blood cultures in a prospective study of 106 HIV?CM coinfected patients. Results. Patients with paradoxical C-IRIS (n = 27), compared with patients with no neurological deterioration (no ND; n = 63), had lower CMP-induced IFN-? production in 24-hour cultures pre-cART and 4 weeks post-cART (P = .0437 and .0257, respectively) and lower CMP-activated CD4+ T-cell counts pre-cART (P = .0178). Patients surviving to 24 weeks had higher proportions of mitogen-activated CD4+ T cells and higher CMP-induced CXCL10 and IL-10 production in 24-hour cultures pre-cART than patients not surviving (P = .0053, .0436 and .0319, respectively). C-IRIS was not associated with higher CMP-specific T-cell responses before or during cART. Conclusion. Greater preservation of T-cell function and higher CMP-induced IL-10 and CXCL10 production before cART are associated with improved survival while on cART. Lower CMP-induced IFN-? production pre-cART, but not higher CMP-specific T-cell responses after cART, were risk factors for C-IRIS.",
author = "Chang, {Christina Catherine} and Andrew Lim and Saleha Omarjee and Levitz, {Stuart M} and Bernadett Gosnell and Spelman, {Tim Denis} and Julian Elliott and Carr, {William H} and Moosa, {Mohamed-Yunus S} and Thumbi Ndung'u and Lewin, {Sharon Ruth} and Martyn French",
year = "2013",
doi = "10.1093/infdis/jit271",
language = "English",
volume = "208",
pages = "898 -- 906",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "6",

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Cryptococcosis-IRIS is associated with lower Cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy. / Chang, Christina Catherine; Lim, Andrew; Omarjee, Saleha; Levitz, Stuart M; Gosnell, Bernadett; Spelman, Tim Denis; Elliott, Julian; Carr, William H; Moosa, Mohamed-Yunus S; Ndung'u, Thumbi; Lewin, Sharon Ruth; French, Martyn.

In: Journal of Infectious Diseases, Vol. 208, No. 6, 2013, p. 898 - 906.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cryptococcosis-IRIS is associated with lower Cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy

AU - Chang, Christina Catherine

AU - Lim, Andrew

AU - Omarjee, Saleha

AU - Levitz, Stuart M

AU - Gosnell, Bernadett

AU - Spelman, Tim Denis

AU - Elliott, Julian

AU - Carr, William H

AU - Moosa, Mohamed-Yunus S

AU - Ndung'u, Thumbi

AU - Lewin, Sharon Ruth

AU - French, Martyn

PY - 2013

Y1 - 2013

N2 - Background. Cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) may be driven by aberrant T-cell responses against cryptococci. We investigated this in human immunodeficiency virus (HIV)?infected patients with treated cryptococcal meningitis (CM) commencing combination antiretroviral therapy (cART). Methods. Mitogen- and cryptococcal mannoprotein (CMP)?activated (CD25+CD134+) CD4+ T cells and -induced production of interferon-gamma (IFN-?), IL-10, and CXCL10 were assessed in whole blood cultures in a prospective study of 106 HIV?CM coinfected patients. Results. Patients with paradoxical C-IRIS (n = 27), compared with patients with no neurological deterioration (no ND; n = 63), had lower CMP-induced IFN-? production in 24-hour cultures pre-cART and 4 weeks post-cART (P = .0437 and .0257, respectively) and lower CMP-activated CD4+ T-cell counts pre-cART (P = .0178). Patients surviving to 24 weeks had higher proportions of mitogen-activated CD4+ T cells and higher CMP-induced CXCL10 and IL-10 production in 24-hour cultures pre-cART than patients not surviving (P = .0053, .0436 and .0319, respectively). C-IRIS was not associated with higher CMP-specific T-cell responses before or during cART. Conclusion. Greater preservation of T-cell function and higher CMP-induced IL-10 and CXCL10 production before cART are associated with improved survival while on cART. Lower CMP-induced IFN-? production pre-cART, but not higher CMP-specific T-cell responses after cART, were risk factors for C-IRIS.

AB - Background. Cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) may be driven by aberrant T-cell responses against cryptococci. We investigated this in human immunodeficiency virus (HIV)?infected patients with treated cryptococcal meningitis (CM) commencing combination antiretroviral therapy (cART). Methods. Mitogen- and cryptococcal mannoprotein (CMP)?activated (CD25+CD134+) CD4+ T cells and -induced production of interferon-gamma (IFN-?), IL-10, and CXCL10 were assessed in whole blood cultures in a prospective study of 106 HIV?CM coinfected patients. Results. Patients with paradoxical C-IRIS (n = 27), compared with patients with no neurological deterioration (no ND; n = 63), had lower CMP-induced IFN-? production in 24-hour cultures pre-cART and 4 weeks post-cART (P = .0437 and .0257, respectively) and lower CMP-activated CD4+ T-cell counts pre-cART (P = .0178). Patients surviving to 24 weeks had higher proportions of mitogen-activated CD4+ T cells and higher CMP-induced CXCL10 and IL-10 production in 24-hour cultures pre-cART than patients not surviving (P = .0053, .0436 and .0319, respectively). C-IRIS was not associated with higher CMP-specific T-cell responses before or during cART. Conclusion. Greater preservation of T-cell function and higher CMP-induced IL-10 and CXCL10 production before cART are associated with improved survival while on cART. Lower CMP-induced IFN-? production pre-cART, but not higher CMP-specific T-cell responses after cART, were risk factors for C-IRIS.

UR - http://jid.oxfordjournals.org/content/208/6/898.full.pdf

U2 - 10.1093/infdis/jit271

DO - 10.1093/infdis/jit271

M3 - Article

VL - 208

SP - 898

EP - 906

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 6

ER -