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dc.date.accessioned | 2022-08-17T15:08:51Z | |
dc.date.available | 2022-08-17T15:08:51Z | |
dc.date.issued | 2017-03-30 | en |
dc.identifier.uri | http://hdl.handle.net/20.500.11910/10861 | |
dc.description.abstract | Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome(TB-IRIS) occurs in 8???54% of South African patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. Improved TB-IRIS molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. We assessed how TB-IRIS status and dexamethasone influence leukocyte proteomic responses to Mycobacterium tuberculosis (Mtb). Patient blood was obtained three weeks post-anti-retroviral therapy initiation. Isolated mononuclear cells were stimulated ex vivo with heat-killed Mtb in the presence/absence of dexamethasone. Mass spectrometry-based proteomic comparison of TB-IRIS and non-IRIS patient-derived cells facilitated generation of hypotheses regarding pathogenesis. Few represented TB-IRIS-group immune-related pathways achieved significant activation, with relative underutilisation of ???inter-cellular interaction??? and ???Fc?? receptor-mediated phagocytosis??? (but a tendency towards apoptosis-related) pathways. Dexamethasone facilitated significant activation of innate-related pathways. Differentially-expressed non-IRIS-group proteins suggest focused and co-ordinated immunological pathways, regardless of dexamethasone status. Findings suggest a relative deficit in TB-IRIS-group responses to and clearance of Mtb antigens, ameliorated by dexamethasone. | en |
dc.format.medium | en | |
dc.subject | TUBERCULOSIS | en |
dc.title | TB-IRIS: proteomic analysis of in vitro PMBC responses to mycobacterium tuberculosis and response modulation by dexamethasone | en |
dc.type | Journal Article | en |
dc.description.version | Y | en |
dc.ProjectNumber | N/A | en |
dc.Volume | 102 | en |
dc.BudgetYear | 2016/17 | en |
dc.ResearchGroup | HIV/AIDS, STIs and TB | en |
dc.SourceTitle | Experimental and Molecular Pathology | en |
dc.ArchiveNumber | 9715 | en |
dc.URL | http://ktree.hsrc.ac.za/doc_read_all.php?docid=18021 | en |
dc.PageNumber | 237-246 | en |
dc.outputnumber | 8606 | en |
dc.bibliographictitle | Bell, L., Peyper, J.M., Garnett, S., Tadokera, R., Wilkinson, R., Meintjies, G. & Blackburn, J.M. (2017) TB-IRIS: proteomic analysis of in vitro PMBC responses to mycobacterium tuberculosis and response modulation by dexamethasone. Experimental and Molecular Pathology. 102:237-246. http://hdl.handle.net/20.500.11910/10861 | en |
dc.publicationyear | 2017 | en |
dc.contributor.author1 | Bell, L. | en |
dc.contributor.author2 | Peyper, J.M. | en |
dc.contributor.author3 | Garnett, S. | en |
dc.contributor.author4 | Tadokera, R. | en |
dc.contributor.author5 | Wilkinson, R. | en |
dc.contributor.author6 | Meintjies, G. | en |
dc.contributor.author7 | Blackburn, J.M. | en |