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 CONCLUSION: We describe, in hitherto unpublished detail, the immunological characterisation of an unmasking TB-IRIS case; we show that thymic output may be compromised at IRIS onset.
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: Paulo S Silveira-Mattos; Gopalan Narendran; Kevan Akrami; Kiyoshi F Fukutani; Selvaraj Anbalagan; Kaustuv Nayak; Sudha Subramanyam; Rajasekaran Subramani; Caian L Vinhaes; Deivide Oliveira-de Souza; Lis R Antonelli; Kumar Satagopan; Brian O Porter; Alan Sher; Soumya Swaminathan; Irini Sereti; Bruno B Andrade Journal: Sci Rep Date: 2019-02-06 Impact factor: 4.379
Authors: Carson M Quinn; Victoria Poplin; John Kasibante; Kyle Yuquimpo; Jane Gakuru; Fiona V Cresswell; Nathan C Bahr Journal: Life (Basel) Date: 2020-10-29
Authors: Ana Carla Pecego; Rodrigo T Amancio; Camila Ribeiro; Emersom C Mesquita; Denise M Medeiros; José Cerbino; Beatriz Grinsztejn; Fernando A Bozza; Andre M Japiassu Journal: BMC Infect Dis Date: 2016-06-10 Impact factor: 3.090