Cryptococcosis-IRIS is associated with lower cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy
Authors
Chang, Christina C.Lim, Andrew
Omarjee, Saleha
Levitz, Stuart M.
Gosnell, Bernadett I.
Spelman, Tim
Elliott, Julian H.
Carr, William H.
Moosa, Mohamed-Yunus S.
Ndung'u, Thumbi
Lewin, Sharon R.
French, Martyn A.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2013-09-01Keywords
AIDS-Related Opportunistic InfectionsAdult
Anti-Retroviral Agents
Antifungal Agents
Antiretroviral Therapy, Highly Active
CD4-Positive T-Lymphocytes
Chemokine CXCL10
Cryptococcus
Fungal Proteins
Humans
Immune Reconstitution Inflammatory Syndrome
therapy
Interferon-gamma
Interleukin-10
Membrane Glycoproteins
Meningitis, Cryptococcal
Multivariate Analysis
Proportional Hazards Models
Prospective Studies
Recombinant Proteins
Risk Factors
South Africa
Immune System Diseases
Immunology of Infectious Disease
Immunoprophylaxis and Therapy
Virus Diseases
Metadata
Show full item recordAbstract
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-gamma), 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-gamma 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-gamma production pre-cART, but not higher CMP-specific T-cell responses after cART, were risk factors for C-IRIS.Source
J Infect Dis. 2013 Sep;208(6):898-906. doi: 10.1093/infdis/jit271. Epub 2013 Jun 12.Link to article on publisher's siteDOI
10.1093/infdis/jit271Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30301PubMed ID
23766525Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1093/infdis/jit271
Scopus Count
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