Author(s): Wilkinson KA, Meintjes G, Seldon R, Goliath R, Wilkinson RJ
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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 CONCLUSION: We describe, in hitherto unpublished detail, the immunological characterisation of an unmasking TB-IRIS case; we show that thymic output may be compromised at IRIS onset.
This article was published in S Afr Med J
and referenced in Journal of Clinical & Cellular Immunology