TB-IRIS pathogenesis and new strategies for intervention: Insights from related inflammatory disorders.
In almost one in five HIV/tuberculosis (TB) co-infected patients, initiation of antiretroviral therapy (ART) is complicated by TB immune reconstitution inflammatory syndrome (TB-IRIS). Corticosteroids have been suggested for treatment of severe cases, however no therapy is currently licensed for TB-IRIS. Hence, there is a strong need for more specific therapeutics, and therefore, a better understanding of TB-IRIS pathogenesis. Immune reconstitution following ART is a precariously balanced functional restoration of adaptive immunity. In those patients predisposed to disease, an incomplete activation of the innate immune system leads to a hyper-inflammatory response that comprises partially overlapping innate, adaptive and effector arms, eventually leading to clinical symptoms. Interestingly, many of these pathological mechanisms are shared by related inflammatory disorders. We here describe therapeutic strategies that originate from these other disciplines and discuss their potential application in TB-IRIS. These new avenues of interventions range from final-phase treatment of symptoms to early-phase prevention of disease onset. In conclusion, we propose a novel approach for the discovery and development of therapeutics, based on an updated model of TB-IRIS pathogenesis. Further experimental studies validating the causal relationships in the proposed model could greatly contribute to providing a solid immunological basis for future clinical trials on TB-IRIS therapeutics.
['Cevaal|Paula M|PM|', 'Bekker|Linda-Gail|LG|', 'Hermans|Sabine|S|']
D056704:Adaptive Immunity D023241:Antiretroviral Therapy, Highly Active D060085:Coinfection D005938:Glucocorticoids D015658:HIV Infections D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D054019:Immune Reconstitution Inflammatory Syndrome D007113:Immunity, Innate D007166:Immunosuppressive Agents D014376:Tuberculosis
Tuberculosis Experimental therapeutics Human immunodeficiency virus (HIV) Immune reconstitution inflammatory syndrome (IRIS) Immunopathogenesis