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dc.contributor.authorChang, Christina C.
dc.contributor.authorLim, Andrew
dc.contributor.authorOmarjee, Saleha
dc.contributor.authorLevitz, Stuart M.
dc.contributor.authorGosnell, Bernadett I.
dc.contributor.authorSpelman, Tim
dc.contributor.authorElliott, Julian H.
dc.contributor.authorCarr, William H.
dc.contributor.authorMoosa, Mohamed-Yunus S.
dc.contributor.authorNdung'u, Thumbi
dc.contributor.authorLewin, Sharon R.
dc.contributor.authorFrench, Martyn A.
dc.date2022-08-11T08:08:31.000
dc.date.accessioned2022-08-23T15:57:52Z
dc.date.available2022-08-23T15:57:52Z
dc.date.issued2013-09-01
dc.date.submitted2015-02-17
dc.identifier.citationJ 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.issn0022-1899 (Linking)
dc.identifier.doi10.1093/infdis/jit271
dc.identifier.pmid23766525
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30301
dc.description.abstractBACKGROUND: 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.isoen_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.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749010/
dc.subjectAIDS-Related Opportunistic Infections
dc.subjectAdult
dc.subjectAnti-Retroviral Agents
dc.subjectAntifungal Agents
dc.subjectAntiretroviral Therapy, Highly Active
dc.subjectCD4-Positive T-Lymphocytes
dc.subjectChemokine CXCL10
dc.subjectCryptococcus
dc.subjectFungal Proteins
dc.subjectHumans
dc.subjectImmune Reconstitution Inflammatory Syndrome
dc.subjecttherapy
dc.subjectInterferon-gamma
dc.subjectInterleukin-10
dc.subjectMembrane Glycoproteins
dc.subjectMeningitis, Cryptococcal
dc.subjectMultivariate Analysis
dc.subjectProportional Hazards Models
dc.subjectProspective Studies
dc.subjectRecombinant Proteins
dc.subjectRisk Factors
dc.subjectSouth Africa
dc.subjectImmune System Diseases
dc.subjectImmunology of Infectious Disease
dc.subjectImmunoprophylaxis and Therapy
dc.subjectVirus Diseases
dc.titleCryptococcosis-IRIS is associated with lower cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy
dc.typeJournal Article
dc.source.journaltitleThe Journal of infectious diseases
dc.source.volume208
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/562
dc.identifier.contextkey6675011
refterms.dateFOA2022-08-23T15:57:52Z
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.submissionpathfaculty_pubs/562
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages898-906


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