P24.14
Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS is thought to be associated with an exaggerated immune response to TB antigens. We compared the recovery of IFNγ responses to TB- and recall-antigens during TB-IRIS. We also explored the contribution of innate cytokine production to TB-IRIS.
Methods: From a prospective cohort study of HIV-TB co-infected patients treated for TB prior to ART initiation, we compared 18 patients who developed TB-IRIS within the first month after ART initiation with 18 non-IRIS patients matched for age, sex and baseline CD4 count. We analyzed IFNγ ELISpot responses to CMV-lysate, influenza antigen A, PPD, ESAT-6, CFP-10 and LPS at pre-ART and IRIS event. CMV, PPD and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex.
Results: At baseline, before initiation of ART, all measured responses were similar between TB-IRIS group and non-IRIS controls. During the TB-IRIS event, IFNγ ELISpot responses to TB or influenza antigens were still comparable between TB-IRIS patients and the non-IRIS patients, but the responses to CMV and LPS were significantly lower in TB-IRIS patients. Production of innate cytokines was similar between IRIS patients and non-IRIS patients. However, IL-6/IL-10 and TNFα/IL-10 ratios were increased during TB-IRIS event upon LPS stimulation, compared to non-IRIS controls.
Conclusions: Our TB-IRIS patients did not display an excessive IFNγ response to TB antigens. However, the reconstitution of recall antigen responses is delayed in the TB-IRIS group. In addition, this study reveals an altered innate cytokine balance during TB-IRIS after LPS stimulation. These data provide further arguments for the involvement of the innate immune system in TB-IRIS pathogenesis.
