Impaired respiratory burst contributes to infections in PKCδ-deficient patients
Anna‐Lena Neehus, Kunihiko Moriya, Alejandro Nieto-Patlán, Tom Le Voyer, Romain Lévy, Ahmet Özen, Elif Karakoç-Aydıner, Safa Barış, Alişan Yıldıran, Engin Altundağ, Manon Roynard, Kathrin Haake, Mélanie Migaud, Karim Dorgham, Guy Gorochov, Laurent Abel, Nico Lachmann, Figen Doğu, Şule Haskoloğlu, Erdal İnce, Jamel El‐Benna, Gülbû Uzel, Ayça Kıykım, Kaan Boztuǧ, Marion Roderick, Mohammad Shahrooei, Paul Brogan, Hassan Abolhassani, Gonca Hancıoğlu, Nima Parvaneh, Alexandre Bélot, Aydan İkincioğulları, Jean‐Laurent Casanova, Anne Puel, Jacinta Bustamante
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.