Cryptococcosis-IRIS is associated with lower cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy
Department of Medicine, Division of Infectious Diseases and Immunology
AIDS-Related Opportunistic Infections; Adult; 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
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.
DOI of Published Version
J Infect Dis. 2013 Sep;208(6):898-906. doi: 10.1093/infdis/jit271. Epub 2013 Jun 12.Link to article on publisher's site
The Journal of infectious diseases
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.; and French, Martyn A., "Cryptococcosis-IRIS is associated with lower cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy" (2013). University of Massachusetts Medical School Faculty Publications. 562.