Proteomic analysis of neutrophils in ANCA-associated vasculitis reveals a dysregulation in proteinase 3-associated proteins such as annexin-A1 involved in apoptotic cell clearance

Judith Everts-Graber, Katherine R. Martin, Nathalie Thieblemont, Julie Mocek, Arnaud Roccabianca, Philippe Chafey, Morgane Le Gall, Pascale Tacnet-Delorme, Chris P. Reutelingsperger, Jean-Marc Naccache, Bernard Bonnotte, Alexandre Karras, Xavier Puechal, Loic Guillevin, Benjamin Terrier, Philippe Frachet, Mauro Perretti, Luc Mouthon, Veronique Witko-Sarsat*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Web of Science)


Granulomatosis with polyangiitis (GPA) is an autoimmune vasculitis associated with anti-neutrophil-cytoplasmic antibodies (ANCA) against proteinase 3 leading to kidney damage. Neutrophils from those patients have increased expression of membrane proteinase 3 during apoptosis. Here we examined whether neutrophils from patients with GPA have dysregulated protein expressions associated with apoptosis. A global proteomic analysis was performed comparing neutrophils from patients with GPA, with healthy individuals under basal conditions and during apoptosis. At disease onset, the cytosolic proteome of neutrophils of patients with GPA before treatment was significantly different from healthy controls, and this dysregulation was more pronounced following ex vivo apoptosis. Proteins involved in cell death/survival were altered in neutrophils of patients with GPA. Several proteins identified were PR3-binding partners involved in the clearance of apoptotic cells, namely calreticulin, annexin-A1 and phospholipid scramblase 1. These proteins form a platform at the membrane of apoptotic neutrophils in patients with GPA but not healthy individuals and this was associated with the clinical presentation of GPA. Thus, our study shows that neutrophils from patients with GPA have an intrinsic dysregulation in proteins involved in apoptotic cell clearance, which could contribute to the unabated inflammation and autoimmunity in GPA. Hence, harnessing these dysregulated pathways could lead to novel biomarkers and targeted therapeutic opportunities to treat kidney disease.

Original languageEnglish
Pages (from-to)397-408
Number of pages12
JournalKidney International
Issue number2
Publication statusPublished - Aug 2019


  • annexin A
  • calreticulin
  • neutrophil
  • phospholipid scramblase 1
  • proteinase 3
  • vasculitis

Cite this