Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged period of time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro coculture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a clinical cellular signature of GCA and suggesting different therapeutic approaches in systemic vascular inflammation.

Original publication

DOI

10.1172/jci.insight.139163

Type

Journal article

Journal

JCI Insight

Publication Date

15/10/2020

Volume

5

Keywords

Autoimmune diseases, Neutrophils, Vascular Biology, Vasculitis, Aged, Antigens, CD, Antigens, Surface, Apoptosis, Autoimmune Diseases, Cell Adhesion Molecules, Cell Line, Cell Lineage, Coculture Techniques, Female, GPI-Linked Proteins, Giant Cell Arteritis, Granulocyte Precursor Cells, Humans, Leukocyte Count, Lewis X Antigen, Male, Middle Aged, Neprilysin, Neutrophils, Oxidation-Reduction, Prognosis, Reactive Oxygen Species, Single-Cell Analysis, Systemic Vasculitis, Temporal Arteries, Vascular Diseases