Impaired respiratory burst contributes to infections in PKCδ-deficient patients
© 2021 Neehus et al..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:218 |
|---|---|
| Enthalten in: |
The Journal of experimental medicine - 218(2021), 9 vom: 06. Sept. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Neehus, Anna-Lena [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Case Reports |
|---|
| Anmerkungen: |
Date Completed 24.11.2021 Date Revised 24.03.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1084/jem.20210501 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM328097756 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM328097756 | ||
| 003 | DE-627 | ||
| 005 | 20231225202228.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1084/jem.20210501 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1093.xml |
| 035 | |a (DE-627)NLM328097756 | ||
| 035 | |a (NLM)34264265 | ||
| 035 | |a (PII)e20210501 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Neehus, Anna-Lena |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impaired respiratory burst contributes to infections in PKCδ-deficient patients |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 24.11.2021 | ||
| 500 | |a Date Revised 24.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 Neehus et al. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Protein Isoforms |2 NLM | |
| 650 | 7 | |a NADPH Oxidases |2 NLM | |
| 650 | 7 | |a EC 1.6.3.- |2 NLM | |
| 650 | 7 | |a PRKCD protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.13 |2 NLM | |
| 650 | 7 | |a Protein Kinase C-delta |2 NLM | |
| 650 | 7 | |a EC 2.7.11.13 |2 NLM | |
| 700 | 1 | |a Moriya, Kunihiko |e verfasserin |4 aut | |
| 700 | 1 | |a Nieto-Patlán, Alejandro |e verfasserin |4 aut | |
| 700 | 1 | |a Le Voyer, Tom |e verfasserin |4 aut | |
| 700 | 1 | |a Lévy, Romain |e verfasserin |4 aut | |
| 700 | 1 | |a Özen, Ahmet |e verfasserin |4 aut | |
| 700 | 1 | |a Karakoc-Aydiner, Elif |e verfasserin |4 aut | |
| 700 | 1 | |a Baris, Safa |e verfasserin |4 aut | |
| 700 | 1 | |a Yildiran, Alisan |e verfasserin |4 aut | |
| 700 | 1 | |a Altundag, Engin |e verfasserin |4 aut | |
| 700 | 1 | |a Roynard, Manon |e verfasserin |4 aut | |
| 700 | 1 | |a Haake, Kathrin |e verfasserin |4 aut | |
| 700 | 1 | |a Migaud, Mélanie |e verfasserin |4 aut | |
| 700 | 1 | |a Dorgham, Karim |e verfasserin |4 aut | |
| 700 | 1 | |a Gorochov, Guy |e verfasserin |4 aut | |
| 700 | 1 | |a Abel, Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Lachmann, Nico |e verfasserin |4 aut | |
| 700 | 1 | |a Dogu, Figen |e verfasserin |4 aut | |
| 700 | 1 | |a Haskologlu, Sule |e verfasserin |4 aut | |
| 700 | 1 | |a İnce, Erdal |e verfasserin |4 aut | |
| 700 | 1 | |a El-Benna, Jamel |e verfasserin |4 aut | |
| 700 | 1 | |a Uzel, Gulbu |e verfasserin |4 aut | |
| 700 | 1 | |a Kiykim, Ayca |e verfasserin |4 aut | |
| 700 | 1 | |a Boztug, Kaan |e verfasserin |4 aut | |
| 700 | 1 | |a Roderick, Marion R |e verfasserin |4 aut | |
| 700 | 1 | |a Shahrooei, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Brogan, Paul A |e verfasserin |4 aut | |
| 700 | 1 | |a Abolhassani, Hassan |e verfasserin |4 aut | |
| 700 | 1 | |a Hancioglu, Gonca |e verfasserin |4 aut | |
| 700 | 1 | |a Parvaneh, Nima |e verfasserin |4 aut | |
| 700 | 1 | |a Belot, Alexandre |e verfasserin |4 aut | |
| 700 | 1 | |a Ikinciogullari, Aydan |e verfasserin |4 aut | |
| 700 | 1 | |a Casanova, Jean-Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Puel, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Bustamante, Jacinta |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of experimental medicine |d 1896 |g 218(2021), 9 vom: 06. Sept. |w (DE-627)NLM000005967 |x 1540-9538 |7 nnns |
| 773 | 1 | 8 | |g volume:218 |g year:2021 |g number:9 |g day:06 |g month:09 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1084/jem.20210501 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 218 |j 2021 |e 9 |b 06 |c 09 | ||