Brief Report: Drugs Implicated in Systemic Autoimmunity Modulate Neutrophil Extracellular Trap Formation

Irizarry-Caro, Jorge A.; Carmona‐Rivera, Carmelo; Schwartz, Daniella M.; Khaznadar, Sami S.; Kaplan, Mariana J.; Grayson, Peter C.

doi:10.1002/art.40372

Cited by 37 publications

(22 citation statements)

References 17 publications

(26 reference statements)

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“…38 Cocaine and levamisole induce the formation of NETs enriched in neutrophil elastase and, potentially, in mitochondrial DNA, which is highly inflammatory. 106 Hydralazine also enhances NET formation, 107 and NETs induced by these drugs or reagents could be a source of antigens leading to ANCA formation. Some drugs, such as hydralazine, induce the promoter demethylation of DNA in T cells, resulting in their activation.…”

Section: [H2] Granulomatosis With Polyangiitismentioning

confidence: 99%

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Pathogenesis and therapeutic interventions for ANCA-associated vasculitis

et al. 2018

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Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a vasculitis that affects systemic small vessels, accompanied by the presence of ANCAs in the serum. This disease entity includes microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and drug-induced AAV. Similar to other autoimmune diseases, AAV develops in patients with a predisposing genetic background who have been exposed to causative environmental factors. The mechanism by which ANCAs cause vasculitis involves ANCA-mediated excessive activation of neutrophils that subsequently release inflammatory cytokines, reactive oxygen species and lytic enzymes. In addition, this excessive activation of neutrophils by ANCAs induces formation of neutrophil extracellular traps (NETs). Although NETs are essential elements in the innate immunity, excessive NET formation is harmful to small vessels. Moreover, NETs are involved not only in ANCA-mediated vascular injury but also in the production of ANCAs themselves. Therefore, a vicious cycle of NET formation and ANCA production is considered to be involved in the pathogenesis of AAV.

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Section: [H2] Granulomatosis With Polyangiitismentioning

confidence: 99%

“…Some drugs, such as hydralazine, induce the promoter demethylation of DNA in T cells, resulting in their activation. 107 Activated T cells contribute to autoantibody production by B cells and plasma cells.…”

Section: [H2] Granulomatosis With Polyangiitismentioning

confidence: 99%

Pathogenesis and therapeutic interventions for ANCA-associated vasculitis

et al. 2018

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“…There is an important contrast that can be realized between the initial work implicating DNA demethylation in T cells (adaptive immunity) and the current work implicating increased NETosis (innate immunity) in drug‐induced autoimmunity . In the former, the implicated mechanism (T cell DNA demethylation) was first described and characterized in drug‐induced autoimmunity and then extended to help understand idiopathic autoimmunity; while in the latter, a role of NETosis was initially described in idiopathic autoimmunity.…”

mentioning

confidence: 95%

“…Both hydralazine and procainamide induce T cell demethylation, T cell autoreactivity in vitro, and T cell–mediated autoimmunity in vivo. The results presented by Irizarry‐Caro et al suggest that both drugs can induce NETosis, implicating the innate immune response in drug‐induced autoimmunity. Hydralazine increased intracellular calcium concentrations, while procainamide induced NETosis through stimulation of neutrophil muscarinic receptors (particularly M 1 and M 3 receptors).…”

mentioning

confidence: 98%