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.

Everts-Graber, Judith; Martin, Katherine R; Thieblemont, Nathalie; Mocek, Julie; Roccabianca, Arnaud; Chafey, Philippe; Le Gall, Morgane; Tacnet-Delorme, Pascale; Reutelingsperger, Chris P; Naccache, Jean-Marc; Bonnotte, Bernard; Karras, Alexandre; Puéchal, Xavier; Guillevin, Loïc; Terrier, Benjamin; Frachet, Philippe; Perretti, Mauro; Mouthon, Luc; Witko-Sarsat, Véronique (2019). 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. Kidney international, 96(2), pp. 397-408. Elsevier 10.1016/j.kint.2019.02.017

[img] Text
1-s2.0-S0085253819302698-main.pdf - Published Version
Restricted to registered users only
Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND).

Download (1MB) | Request a copy

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Everts-Graber, Judith

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1523-1755

Publisher:

Elsevier

Language:

English

Submitter:

Burkhard Möller

Date Deposited:

08 Nov 2019 08:52

Last Modified:

08 Nov 2019 08:59

Publisher DOI:

10.1016/j.kint.2019.02.017

PubMed ID:

31142442

Uncontrolled Keywords:

annexin A calreticulin neutrophil phospholipid scramblase 1 proteinase 3 vasculitis

BORIS DOI:

10.7892/boris.134775

URI:

https://boris.unibe.ch/id/eprint/134775

Actions (login required)

Edit item Edit item
Provide Feedback