Neehus, A-L;
Moriya, K;
Nieto-Patlán, A;
Le Voyer, T;
Lévy, R;
Özen, A;
Karakoc-Aydiner, E;
... Bustamante, J; + view all
(2021)
Impaired respiratory burst contributes to infections in PKCδ-deficient patients.
Journal of Experimental Medicine
, 218
(9)
, Article e20210501. 10.1084/jem.20210501.
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Abstract
Patients with autosomal recessive protein kinase C δ (PKCδ) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also suffer from recurrent infections that overlap with those seen in patients with chronic granulomatous disease (CGD), a disease caused by defects of the phagocyte NADPH oxidase and a lack of reactive oxygen species (ROS) production. We studied an international cohort of 17 PKCδ-deficient patients and found that their EBV-B cells and monocyte-derived phagocytes produced only small amounts of ROS and did not phosphorylate p40phox normally after PMA or opsonized Staphylococcus aureus stimulation. Moreover, the patients' circulating phagocytes displayed abnormally low levels of ROS production and markedly reduced neutrophil extracellular trap formation, altogether suggesting a role for PKCδ in activation of the NADPH oxidase complex. Our findings thus show that patients with PKCδ deficiency have impaired NADPH oxidase activity in various myeloid subsets, which may contribute to their CGD-like infectious phenotype.
| Type: | Article |
|---|---|
| Title: | Impaired respiratory burst contributes to infections in PKCδ-deficient patients |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1084/jem.20210501 |
| Publisher version: | http://dx.doi.org/10.1084/jem.20210501 |
| Language: | English |
| Additional information: | © 2021 Neehus et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10131996 |
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