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

Amsler, Jennifer; Everts-Graber, Judith; Martin, Katherine R; Roccabianca, Arnaud; Lopes, Chloé; Tourneur, Léa; Mocek, Julie; Karras, Alexandre; Naccache, Jean-Marc; Bonnotte, Bernard; Samson, Maxime; Hanslik, Thomas; Puéchal, Xavier; Terrier, Benjamin; Guillevin, Loïc; Néel, Antoine; Mouthon, Luc; Witko-Sarsat, Véronique (2023). Dysregulation of neutrophil oxidant production and interleukin-1-related cytokines in granulomatosis with polyangiitis. (In Press). Rheumatology Oxford University Press 10.1093/rheumatology/kead578

Text kead578.pdf - Accepted Version Restricted to registered users only until 9 November 2024. Available under License Publisher holds Copyright. Download (1MB) | Request a copy

OBJECTIVES

Neutrophils play a key role in ANCA-associated vasculitis, both as targets of autoimmunity and facilitators of vascular damage. In granulomatosis with polyangiitis (GPA), 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 the inflammasome and IL-1-related cytokines. We aimed to analyse the ROS production in neutrophils from patients with GPA and investigate its association with IL-1-related cytokines and the autoantigen proteinase 3 (PR3).

METHODS

Seventy-two GPA patients with disease flare were included in the NEUTROVASC prospective cohort study. ROS production was evaluated in whole blood of patients with active GPA and compared with 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 analyzed.

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 the inflammasome in neutrophils from patients with GPA are disturbed and may be a potential therapeutic target.

CLINICAL TRIAL REGISTRATION NUMBER

NCT01862068, clinicaltrials.gov, https://www.clinicaltrials.gov.

Interest & Impact

Downloads

0 since deposited on 13 Nov 2023
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item