Immunological characterisation of an unmasking TB-IRIS case.
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.


OBJECTIVE
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.


CONCLUSIONS
We describe, in hitherto unpublished detail, the immunological characterisation of an unmasking TB-IRIS case; we show that thymic output may be compromised at IRIS onset.
Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town. katalin.wilkinson@uct.ac.za
Katalin A
KA
Wilkinson
Graeme
G
Meintjes
Ronnett
R
Seldon
Rene
R
Goliath
Robert John
RJ
Wilkinson
D000328:Adult; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D048588:Benzoxazines / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003521:Cyclopropanes; D016207:Cytokines / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced / Q000276:immunology*; D019259:Lamivudine / Q000009:adverse effects; D008297:Male; D009894:Opportunistic Infections / Q000150:complications*; D018119:Stavudine / Q000009:adverse effects; D013935:Thymic Factor, Circulating / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000150:complications*
D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D016207:Cytokines; D019259:Lamivudine; D013935:Thymic Factor, Circulating; D018119:Stavudine; C098320:efavirenz