Bell, Liam, Peyper, Janique M., Garnett, Shaun, Tadokera, Rebecca ORCID: https://orcid.org/0000-0001-5195-2376, Wilkinson, Robert, Meintjes, Graeme and Blackburn, Jonathan M. (2017) TB-IRIS: Proteomic analysis of in vitro PBMC responses to Mycobacterium tuberculosis and response modulation by dexamethasone. Experimental and molecular pathology, 102 (2). pp. 237-246.

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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 under-utilisation of “inter-cellular interaction” and “Fcγ 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.

Item Type:	Article
Status:	Published
DOI:	10.1016/j.yexmp.2017.02.008
School/Department:	School of Science, Technology and Health
URI:	https://ray.yorksj.ac.uk/id/eprint/9375

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