Dysregulation of neutrophil oxidant production and interleukin-1-related cytokines in granulomatosis with polyangiitis.

Autor:	Amsler J; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France.; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Everts-Graber J; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France.; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Martin KR; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France.; Inflammation Division, WEHI, and Department of Medical Biology, University of Melbourne, Parkville, Australia., Roccabianca A; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France., Lopes C; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France., Tourneur L; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France., Mocek J; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France., Karras A; Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France., Naccache JM; Department of Pulmonology-Allergology-Thoracic Oncology, Groupe Hospitalier Paris Saint Joseph, Paris, France., Bonnotte B; Service de Médecine Interne et Immunologie Clinique, CHU Dijon, Dijon, France., Samson M; Service de Médecine Interne et Immunologie Clinique, CHU Dijon, Dijon, France., Hanslik T; Service de Médecine Interne, Hôpital Ambroise-Paré, AP-HP, Boulogne Billancourt, France., Puéchal X; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France.; Department of Internal Medicine, Centre de Référence pour les Maladies Systémiques Autoimmunes Rares d'Ile de France, Cochin Hospital, AP-HP, Paris, France., Terrier B; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France.; Department of Internal Medicine, Centre de Référence pour les Maladies Systémiques Autoimmunes Rares d'Ile de France, Cochin Hospital, AP-HP, Paris, France., Guillevin L; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France.; Department of Internal Medicine, Centre de Référence pour les Maladies Systémiques Autoimmunes Rares d'Ile de France, Cochin Hospital, AP-HP, Paris, France., Néel A; Service de Médecine Interne, CHU Nantes, Nantes, France.; CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, Nantes, France., Mouthon L; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France.; Department of Internal Medicine, Centre de Référence pour les Maladies Systémiques Autoimmunes Rares d'Ile de France, Cochin Hospital, AP-HP, Paris, France., Witko-Sarsat V; INSERM U1016, Institut Cochin, CNRS UMR 8104, Paris, France.; Université Paris Cité, Paris, France.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Aug 01; Vol. 63 (8), pp. 2249-2258.
DOI:	10.1093/rheumatology/kead578
Abstrakt:	Objectives: Neutrophils play a key role in ANCA-associated vasculitis, both as targets of autoimmunity and as facilitators of vascular damage. In granulomatosis with polyangiitis (GPA), the data regarding the production of reactive oxygen species (ROS) in neutrophils are unclear. Further, recent data suggests that ROS production could have an anti-inflammatory effect through the regulation of inflammasomes and IL-1-related cytokines. We aimed to analyse ROS production in neutrophils from patients with GPA and investigate its association with IL-1-related cytokines and the autoantigen PR3. Methods: Seventy-two GPA patients with disease flare were included in the NEUTROVASC prospective cohort study. ROS production in whole blood of patients with active GPA was evaluated and compared with that in the same patients in remission or healthy controls. Associations between ROS production, PR3 membrane expression on neutrophils, serum levels of IL-1-related cytokines as well as inflammasome-related proteins were analysed. Results: We observed a robust defect in ROS production by neutrophils from patients with active GPA compared with healthy controls, independent of glucocorticoid treatment. Serum levels of IL-1-related cytokines were significantly increased in GPA patients, particularly in patients with kidney involvement, and levels of these cytokines returned to normal after patients achieved remission. Further, inflammasome-related proteins were significantly dysregulated in the cytosol of neutrophils as well as the serum from GPA patients. Conclusion: Our data suggests that ROS production and regulation of inflammasomes in neutrophils from patients with GPA are disturbed and may be a potential therapeutic target. Trial Registration: ClinicalTrials.gov, https://www.clinicaltrials.gov, NCT01862068. (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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