a-high-throughput-assay-to-assess-quantify-neutrophil-extracellular

A High-throughput Assay to Assess and Quantify Neutrophil Extracellular Trap Formation

Neutrophil extracellular traps (NETs) are immunogenic extracellular DNA structures that can be released by neutrophils upon a wide variety of triggers. ...

Leiden University Medical Center

Azathioprine-induced eosinophilic myocarditis in a patient with ANCA-associated vasculitis.

Neutrophil extracellular traps (NETs) are auto-antigenic strands of extracellular DNA covered with myeloperoxidase (MPO) and proteinase3 (PR3) that can be a source for the formation of anti-neutrophil cytoplasmic autoantibodies (ANCAs). The presence of NETs was recently demonstrated in renal tissue of patients with ANCA-associated vasculitis (AAV). NET formation was enhanced in AAV, suggesting that MPO-ANCA could trigger NET formation, supporting a vicious circle placing NETs in the center of AAV pathogenesis. Here we investigated NET formation in 99 patients with AAV by a novel highly sensitive and automated assay. There was a significant excess of ex vivo NET formation in both MPO-ANCA- and PR3-ANCA-positive patients with AAV compared to healthy individuals. Excessive NET formation did not correlate with serum ANCA levels. Likewise, immunoglobulin G depletion had no effect on excessive NET formation in patients with AAV, indicating an ANCA-independent process. Next, we explored the relation of excessive NET formation to clinical disease in ten patients with AAV and showed that excessive NET formation was predominantly found during active disease, more so than during remission. Excessive NET formation was found in patients with AAV hospitalized for disease relapse but not during severe infection. Thus, excessive NET formation in AAV is independent of ANCA, and an excess of ex vivo NET formation was related to active clinical disease in patients with AAV and a marker of autoimmunity rather than infection.

Excessive neutrophil extracellular trap formation in ANCA-associated vasculitis is independent of ANCA.

In systemic lupus erythematosus (SLE) patients, excessive formation of neutrophil extracellular traps (NETs) is observed and their degradation is impaired. In vitro, immune complexes (ICx) trigger NET formation while NET-derived DNA is a postulated autoantigen for anti-nuclear autoantibodies (ANAs), found in SLE. Based on these self-perpetuating mechanisms in SLE, this study investigates whether interfering with ICx formation using a combination of rituximab (RTX) and belimumab (BLM) could decrease NET formation and ameliorate disease.

Article	Year
Azathioprine-induced eosinophilic myocarditis in a patient with ANCA-associated vasculitis. Clinical and experimental rheumatology\| PubMed ID: 26950304	2016
Excessive neutrophil extracellular trap formation in ANCA-associated vasculitis is independent of ANCA. Kidney international\| PubMed ID: 29606398	2018
The NET-effect of combining rituximab with belimumab in severe systemic lupus erythematosus. Journal of autoimmunity\| PubMed ID: 29636274	2018

Y.K. Onno Teng

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