Tadokera, Rebecca ORCID: https://orcid.org/0000-0001-5195-2376, Meintjes, Graeme A., Wilkinson, Katalin A., Skolimowska, Keira H., Walker, Naomi, Friedland, Jon S., Maartens, Gary, Elkington, Paul T. G. and Wilkinson, Robert J. (2013) Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome. European journal of immunology, 44 (1). pp. 127-136.

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Abstract

The HIV-TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) can complicate combined treatments for HIV-1 and TB. Little is known about tissue damage in TB-IRIS. Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix and consequently may play a role in such immunopathology. Here we investigated the involvement of MMPs in TB-IRIS. We determined MMP transcript abundance and secreted protein in Mycobacterium tuberculosis stimulated PBMCs from 22 TB-IRIS patients and 22 non-IRIS controls. We also measured MMP protein levels in corresponding serum and the effect of prednisone — which reduces the duration of symptoms in IRIS patients — or placebo treatment on MMP transcript and circulating MMP protein levels. PBMCs from TB-IRIS had increased MMP-1, -3, -7, and -10 transcript levels when compared with those of controls at either 6 or 24 h. Similarly, MMP-1, -3, -7, and -10 protein secretion in stimulated cultures was higher in TB-IRIS than in controls. Serum MMP-7 concentration was elevated in TB-IRIS and 2 weeks of corticosteroid therapy decreased this level, although not significantly. TB-IRIS is associated with a distinct pattern of MMP gene and protein activation. Modulation of dysregulated MMP activity may represent a novel therapeutic approach to alleviate TB-IRIS in HIV-TB patients undergoing treatment.

Item Type:	Article
Status:	Published
DOI:	https://doi.org/10.1002/eji.201343593
School/Department:	School of Science, Technology and Health
URI:	https://ray.yorksj.ac.uk/id/eprint/9377

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