Cryptococcosis-IRIS is associated with lower cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy
dc.contributor.author | Chang, Christina C. | |
dc.contributor.author | Lim, Andrew | |
dc.contributor.author | Omarjee, Saleha | |
dc.contributor.author | Levitz, Stuart M. | |
dc.contributor.author | Gosnell, Bernadett I. | |
dc.contributor.author | Spelman, Tim | |
dc.contributor.author | Elliott, Julian H. | |
dc.contributor.author | Carr, William H. | |
dc.contributor.author | Moosa, Mohamed-Yunus S. | |
dc.contributor.author | Ndung'u, Thumbi | |
dc.contributor.author | Lewin, Sharon R. | |
dc.contributor.author | French, Martyn A. | |
dc.date | 2022-08-11T08:08:31.000 | |
dc.date.accessioned | 2022-08-23T15:57:52Z | |
dc.date.available | 2022-08-23T15:57:52Z | |
dc.date.issued | 2013-09-01 | |
dc.date.submitted | 2015-02-17 | |
dc.identifier.citation | J Infect Dis. 2013 Sep;208(6):898-906. doi: 10.1093/infdis/jit271. Epub 2013 Jun 12.<a href="http://dx.doi.org/10.1093/infdis/jit271">Link to article on publisher's site</a> | |
dc.identifier.issn | 0022-1899 (Linking) | |
dc.identifier.doi | 10.1093/infdis/jit271 | |
dc.identifier.pmid | 23766525 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/30301 | |
dc.description.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-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. | |
dc.language.iso | en_US | |
dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23766525&dopt=Abstract">Link to Article in PubMed</a> | |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749010/ | |
dc.subject | AIDS-Related Opportunistic Infections | |
dc.subject | Adult | |
dc.subject | Anti-Retroviral Agents | |
dc.subject | Antifungal Agents | |
dc.subject | Antiretroviral Therapy, Highly Active | |
dc.subject | CD4-Positive T-Lymphocytes | |
dc.subject | Chemokine CXCL10 | |
dc.subject | Cryptococcus | |
dc.subject | Fungal Proteins | |
dc.subject | Humans | |
dc.subject | Immune Reconstitution Inflammatory Syndrome | |
dc.subject | therapy | |
dc.subject | Interferon-gamma | |
dc.subject | Interleukin-10 | |
dc.subject | Membrane Glycoproteins | |
dc.subject | Meningitis, Cryptococcal | |
dc.subject | Multivariate Analysis | |
dc.subject | Proportional Hazards Models | |
dc.subject | Prospective Studies | |
dc.subject | Recombinant Proteins | |
dc.subject | Risk Factors | |
dc.subject | South Africa | |
dc.subject | Immune System Diseases | |
dc.subject | Immunology of Infectious Disease | |
dc.subject | Immunoprophylaxis and Therapy | |
dc.subject | Virus Diseases | |
dc.title | Cryptococcosis-IRIS is associated with lower cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy | |
dc.type | Journal Article | |
dc.source.journaltitle | The Journal of infectious diseases | |
dc.source.volume | 208 | |
dc.source.issue | 6 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/faculty_pubs/562 | |
dc.identifier.contextkey | 6675011 | |
refterms.dateFOA | 2022-08-23T15:57:52Z | |
html.description.abstract | <p>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).</p> <p>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.</p> <p>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.</p> <p>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.</p> | |
dc.identifier.submissionpath | faculty_pubs/562 | |
dc.contributor.department | Department of Medicine, Division of Infectious Diseases and Immunology | |
dc.source.pages | 898-906 |