Author(s): Albuquerque, Adriana S. ; Fernandes, Susana M. ; Tendeiro, Rita ; Cheynier, Rémi ; Lucas, Margarida ; Silva, Susana L. ; Victorino, Rui M. M. ; Sousa, Ana E.
Date: 2017
Persistent ID: http://hdl.handle.net/10451/28767
Origin: Repositório da Universidade de Lisboa
Subject(s): Primary immunodeficiency; Chronic granulomatous disease; Genetic phagocytic defect; Reactive oxygen species; CD4 T-cell lymphopenia; Immune senescence
Chronic granulomatous disease (CGD) results from primary defects in phagocytic reactive oxygen species (ROS) production. T-cell evaluation is usually neglected during patients' follow-up, although T-cell depletion has been reported in CGD through unknown mechanisms. We describe here a 36-year-old patient with X-linked CGD with severe CD4 T-cell depletion <200 CD4 T-cells/μl, providing insights into the mechanisms that underlie T-cell loss in the context of oxidative burst defects. In addition to the typical infections, the patient featured a progressive T-cell loss associated with persistent lymphocyte activation, expansion of interleukin (IL)-17-producing CD4 T-cells, and impaired thymic activity, leading to a reduced replenishment of the T-cell pool. A relative CD4 depletion was also found at the gut mucosal level, although no bias to IL-17-production was documented. This immunological pattern of exhaustion of immune resources favors prompt, potentially curative, therapeutic interventions in CGD patients, namely, stem-cell transplantation or gene therapy. Moreover, this clinical case raises new research questions on the interplay of ROS production and T-cell homeostasis and immune senescence.
