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NDORMS researchers identify a subset of immune cells that could be a new therapeutic target to treat inflamed blood vessels in Giant Cell Arteritis (GCA) and other forms of inflammatory vascular disease.

Blood cells

The research, led by Prof Irina Udalova (Kennedy Institute) in collaboration with Prof Raashid Luqmani (Botnar Research Centre) and published in JCI Insight, identified an immature population of neutrophils that accumulates in the blood of GCA patients and attaches to the arterial vessel wall. The researchers found that reactive oxygen species (ROS) released by these neutrophils trigger changes in blood vessel cells, which could represent an early event in the development of inflammatory lesions.

GCA is one of a group of systemic vasculitides that causes inflammation in the large vessels in the head and neck. It is becoming increasingly common in an ageing population and can lead to significant health problems if untreated, including loss of sight.

To understand more about the cause of GCA, Irina's team analysed individual white blood cells in blood samples from GCA patients. They discovered that the main expansion in cell populations in active GCA was in neutrophils. Dr Lihui Wang, the first author on the paper says: "These cells are normally meant to fight microbes. But to do so they produce reactive oxygen species, among other mediators, which could be pathogenic in prolonged inflammatory conditions. Fully mature neutrophils quickly die, but immature neutrophils that in health are confounded to the bone marrow, live for much longer."

Irina continues, "We were excited to see this population of cells expanded in GCA, infiltrated blood vessels and produced large quantities of ROS. It damaged endothelial barrier and led to endothelial leakage. The same immature neutrophils have recently been linked to severe COVID-19, but the mechanisms are unknown. Thus, our discovery may shed light on the vascular pathology observed in COVID-19 as well."

The research was funded by Versus Arthritis and Oxford-Celgene fellowship programme and the Wellcome Trust.