Patients with subtypes of small-vessel antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis and microscopic polyangiitis, as well as those with certain types of large-vessel vasculitis (LVV), may have elevated circulating levels of neutrophil-activating factors, according to an article published in Clinical Immunology.

In this study, the researchers primarily assessed the levels of neutrophil extracellular traps (NETs) in plasma samples of patients with AAV and LVV. They investigated whether NET levels were associated with disease activity and inflammatory markers in vasculitis, as well as each patient’s capacity to degrade NETs.

Another study objective was to evaluate the levels of anti-NET and anti-histone antibodies as well as the correlation of thrombospondin 1 with NETs and thromboembolism.

The study authors analyzed the plasma samples of 30 healthy controls and 123 patients with granulomatosis with polyangiitis, 61 with microscopic polyangiitis, 58 with Takayasu’s arteritis (an LVV subtype), and 68 with giant cell arteritis (another type of LVV), at times of remission or activity. They assessed the disease severity through physician global assessment, which strongly correlates with the Birmingham vasculitis activity score.

According to the results, elevated NET levels were reported in patients with all 4 vasculitis subtypes during both the disease flares and remission. All cohorts demonstrated impaired NET degradation, while those with giant cell arteritis and microscopic polyangiitis also had anti-NET IgG antibodies.

In patients with Takayasu’s arteritis, the presence of anti-histone antibodies was correlated with the presence of NETs. Moreover, thrombospondin 1 levels were increased in all patients with vasculitis and associated with the formation of NETs.

Read more about AAV diagnosis

“Levels of NETs do not seem to be a reliable indicator of disease activity in systemic vasculitis, but they may indicate chronic low-grade inflammation that could lead to organ damage,” Michailidou and colleagues wrote.

“Our findings highlight both excessive NET formation and defective NET clearance as common mechanisms in vasculitis, supporting the development of novel preventative treatment strategies against NET formation for these diseases,” they wrote. “Specific inhibitors of protein kinase C, c-rapidly accelerated fibrosarcoma kinase and mitogen-activated protein kinase can prevent NET formation, by blocking the downregulation of the anti-apoptotic protein Mcl-1, highlighting the seminal role of the Raf-MEK-ERK pathway in NET formation.”

NETs, comprised of decondensed chromosomal DNA, citrullinated histones, granule proteins, lactoferrin, cathepsin G and LL37, have a significant role in host defense as well as the pathogenesis of many autoimmune diseases.


Michailidou D, Kuley R, Wang T, et al. Neutrophil extracellular trap formation in anti-neutrophil cytoplasmic antibody-associated and large-vessel vasculitis. Clin Immunol. Published online March 4, 2023. doi:10.1016/j.clim.2023.109274