期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 9, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20210501
关键词
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资金
- Yale Center for Mendelian Genomics - National Human Genome Research Institute [UM1HG006504]
- National Institute of Allergy and Infectious Diseases [5R01AI089970, 5R37AI095983, R01AI127564-01]
- National Center for Research Resources
- National Center for Advancing Translational Sciences of the National Institutes of Health [8UL1TR001866]
- Rockefeller University
- St. Giles Foundation
- INSERM
- University of Paris
- French Foundation for Medical Research [EQU201903007798]
- Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID]
- SCOR Corporate Foundation for Science
- French National Research Agency (ANR) under the Investments for the future program [ANR-10-IAHU-01]
- ANR-IFNPHOX [ANR-13-ISV3-0001-01]
- ANR-GENMSMD [ANR-16-CE17-0005-01]
- ANR-GENCMCD [ANR-11-BSV3-005-01]
- ANR-HGDIFD [ANR-14-CE15-0006-01]
- Bettencourt Schueller Foundation
- International PhD program of the Imagine Institute
- Japanese Foundation
- EURO-CMC project [ANR-14-RARE-0005-02]
- Societe Nationale Francaise de Medecine Interne (Bourse Marcel Simon)
- INSERM PhD program for medical doctors (poste d'accueil INSERM)
- Fulbright grant (Franco-American commission)
- MD-PhD program of Imagine Institute
- Consejo Nacional de Ciencia y Tecnologa National PhD Fellowship Program
- National Institute for Health Research Biomedical Research Centre
- Great Ormond Street Hospital Charity
- Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy [EXC 2155, 390874280]
- REBIRTH Center for Translational Regenerative Medicine through the State of Lower Saxony [MWK: ZN3440]
- Agence Nationale de la Recherche (ANR) [ANR-14-CE15-0006] Funding Source: Agence Nationale de la Recherche (ANR)
Patients with autosomal recessive protein kinase C delta deficiency exhibit childhood-onset autoimmunity and recurrent infections similar to chronic granulomatous disease (CGD) patients, possibly due to impaired NADPH oxidase activity.
Patients with autosomal recessive protein kinase C delta (PKC delta) 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 PKC delta-deficient patients and found that their EBV-B cells and monocyte-derived phagocytes produced only small amounts of ROS and did not phosphorylate p40(phox) 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 PKC delta in activation of the NADPH oxidase complex. Our findings thus show that patients with PKC delta deficiency have impaired NADPH oxidase activity in various myeloid subsets, which may contribute to their CGD-like infectious phenotype.
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