Centenary of the UCT Faculty of Health Sciences

Immunological characterisation of an unmasking TB-IRIS case

Katalin A Wilkinson, Graeme Meintjes, Ronnett Seldon, Rene Goliath, Robert John Wilkinson

Abstract


Background. Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an early complication of combination antiretroviral therapy (cART). Two forms are recognised: (i) paradoxical – recurrent or new TB symptoms develop after cART initiation in patients receiving TB treatment prior to cART; and (ii) unmasking TB-IRIS – active TB presents within 3 months of cART in patients not receiving TB treatment at cART initiation. The latter has heightened clinical manifestations and a marked inflammatory presentation.
Aim. To gain insight into the immune pathogenesis of a case of unmasking TB-IRIS.
Methods. The patient was recruited when starting cART and followed up at 4, 12 and 24 weeks of treatment. Peripheral blood mononuclear cells were used for flow cytometry.
Results. Immunological analysis indicated increased CD4+ T-cell proportions from 1.1% at baseline to 14% at 24 weeks (the CD4 count increased from 4 cells/µl at baseline to 41 cells/µl at 24 weeks). HIV viral load fell from 460 774 to 1 405 copies/ml during the same period. The proportion of TB antigen (PPD)-specific CD4+IFN-γ+ cells increased from 0.4% at baseline and 4 weeks (IRIS onset) to 7.8% at 12 weeks (after resolution of the IRIS episode); this fell to 0.7% at 24 weeks. The surface phenotype of CD4+IFN-γ+ cells during the episode was CD45RO+, CD45RA-, CCR7-, CD62L-, CCR5+/- and CD69-. We found a distorted balance between central memory and effector memory T-cells at cART commencement that might have predisposed the patient to unmasking TB-IRIS. We showed that this might have reflected compromised thymic output.
Discussion. While it has been suggested that tuberculin-specific Th1-responses induce TB-IRIS in HIV co-infected patients, our data in this case indicated that these cells were expanded only after IRIS onset and were therefore not inducing TB-IRIS.
Conclusion. We describe, in hitherto unpublished detail, the immunological characterisation of an unmasking TB-IRIS case; we show that thymic output may be compromised at IRIS onset.

Authors' affiliations

Katalin A Wilkinson, Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town

Graeme Meintjes, Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, and Infectious Diseases Unit, G F Jooste Hospital, Cape Town, South Africa, and Division of Medicine, Imperial College London

Ronnett Seldon, Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town

Rene Goliath, Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town

Robert John Wilkinson, Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, South Africa; Infectious Diseases Unit, G F Jooste Hospital, Cape Town, South Africa; MRC National

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Keywords

Tuberculosis, HIV, TB-IRIS

Cite this article

South African Medical Journal 2012;102(6):512-517.

Article History

Date submitted: 2011-10-07
Date published: 2012-03-02

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