Investigating the molecular pathogenesis of tuberculosis-associated immune reconstitution inflammatory syndrome
type: CreativeWork
description: Thesis summary This thesis comprises a series of studies that adapted a reverse translational approach to investigate the mechanisms underlying the immunopathogenesis of paradoxical tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS). Paradoxical TB-IRIS is an aberrant immune response targeted against Mycobacterium tuberculosis or its residual antigens in patients with advanced human immunodeficiency virus (HIV) infection shortly after commencement of antiretroviral therapy (ART). TB-IRIS is characterized by hyperinflammation and tissue damage. Pulmonary and lymph node involvement are the most common clinical manifestations. The incidence of TB-IRIS can reach up to 54% in settings where both HIV and TB are endemic, such as the sub-Saharan-Africa region of the African continent. Approximately 25% of patients with paradoxical TB-IRIS will require hospitalization for syndromic management. The management and prevention of paradoxical TB-IRIS rely on the use of anti-inflammatories such as immunosuppressive corticosteroid intervention, which is associated with an increased risk of Kaposi sarcoma. Paradoxical TB-IRIS is potentially fatal, with cases of central nervous system (CNS) involvement having the highest fatalities (up to 56%). The underlying cause of paradoxical TB-IRIS is thought to arise from a dysregulated hyperinflammatory immune response during ART-mediated immune recovery, although the causal mechanisms and associated molecular pathways are incompletely defined. This knowledge gap compromises efforts to develop new diagnostic and prognostic modalities as well as safer and more efficacious therapeutic interventions. This served as the rationale for undertaking the studies reported in this thesis. Using clinical samples from the PredART intervention trial and the TB-ART observational study, this thesis investigated the cellular and molecular determinants of paradoxical TB-IRIS. Conventional scientific hypothesis-based approaches as wel…
abstract: Thesis summary This thesis comprises a series of studies that adapted a reverse translational approach to investigate the mechanisms underlying the immunopathogenesis of paradoxical tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS). Paradoxical TB-IRIS is an aberrant immune response targeted against Mycobacterium tuberculosis or its residual antigens in patients with advanced human immunodeficiency virus (HIV) infection shortly after commencement of antiretroviral therapy (ART). TB-IRIS is characterized by hyperinflammation and tissue damage. Pulmonary and lymph node involvement are the most common clinical manifestations. The incidence of TB-IRIS can reach up to 54% in settings where both HIV and TB are endemic, such as the sub-Saharan-Africa region of the African continent. Approximately 25% of patients with paradoxical TB-IRIS will require hospitalization for syndromic management. The management and prevention of paradoxical TB-IRIS rely on the use of anti-inflammatories such as immunosuppressive corticosteroid intervention, which is associated with an increased risk of Kaposi sarcoma. Paradoxical TB-IRIS is potentially fatal, with cases of central nervous system (CNS) involvement having the highest fatalities (up to 56%). The underlying cause of paradoxical TB-IRIS is thought to arise from a dysregulated hyperinflammatory immune response during ART-mediated immune recovery, although the causal mechanisms and associated molecular pathways are incompletely defined. This knowledge gap compromises efforts to develop new diagnostic and prognostic modalities as well as safer and more efficacious therapeutic interventions. This served as the rationale for undertaking the studies reported in this thesis. Using clinical samples from the PredART intervention trial and the TB-ART observational study, this thesis investigated the cellular and molecular determinants of paradoxical TB-IRIS. Conventional scientific hypothesis-based approaches as wel…
author: Moseki, Raymond
language: en
keywords: Tuberculosis, TB, antiretroviral therapy, ART, human immunodeficiency virus, HIV, TB-IRIS, tuberculosis associated immune reconstitution inflammatory syndrome
date published: 2025
date modified: 2026-07-22T22:22:39Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Medicine

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11427/42474