Formation and Disordered Degradation of Neutrophil Extracellular Traps in Necrotizing Lesions of Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis

Masuda, Sakiko; Nonokawa, Mayu; Futamata, Emika; Nishibata, Yuka; Iwasaki, Shigeo; Tsuji, Takeshi; Hatanaka, Yutaka; Nakazawa, Daigo; Tanaka, Satoshi; Tomaru, Utano; Kawakami, Tamihiro; Atsumi, Tatsuya; Ishizu, Akihiro

doi:10.1016/j.ajpath.2019.01.007

Cited by 25 publications

(14 citation statements)

References 25 publications

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“…Analysis of NETs showed weaker degradation of extracellular DNA in eosinophylic granulomatosis with polyangiitis associated with SLE patients. This phenomenon appears to be a characteristic of autoimmune disease (30,31). DNase I was inhibited by complement over-activation as well as excessive deposition of the complement protein, C1q, which resulted in the inability to degrade NETs (13).…”

Section: Discussionmentioning

confidence: 99%

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis

Chen

Zou

et al. 2021

Front. Immunol.

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ObjectivesThis aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children.MethodsWe performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked in vitro. Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed.ResultsCirculating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples.ConclusionsOur data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.

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Section: Discussionmentioning

confidence: 99%

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis

Chen

Zou

et al. 2021

Front. Immunol.

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“…CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made The copyright holder for this preprint this version posted February 11, 2021. ; https://doi.org/10.1101/2021.02.09.430558 doi: bioRxiv preprint and necrotizing granulomas (10). Generation of the NETs in necrotizing granulomas of pulmonary tuberculosis could be mediated by the abilities of immune complexes to induce NET release in neutrophils (8).…”

Section: Discussionmentioning

confidence: 99%

“…Necrotizing granuloma is a hallmark of pulmonary tuberculosis and is shown to have abundant NETs (10). Abundant NETs have also been reported in necrotizing granulomas from patients with granulomatosis with polyangiitis, a small vessel vasculitis condition in which neutrophils and NETs were associated with necrosis of blood vessels and necrotizing granulomas (10). Generation of the NETs in necrotizing granulomas of pulmonary tuberculosis could be mediated by the abilities of immune complexes to induce NET release in neutrophils (8).…”

Section: Discussionmentioning

confidence: 99%

Immune deposit and vasculopathy in metabolic-active lung tissues of patients with pulmonary tuberculosis

Wang

Wen

et al. 2021

Preprint

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Metabolic activity in pulmonary lesion is associated with disease severity and relapse risk in tuberculosis. However, the nature of the metabolic activity associated with tuberculosis in humans remains unclear. Previous works indicate that tuberculosis bears resemblance transcriptionally with systemic lupus erythematosus in peripheral blood, except that the plasma cell component was absent in tuberculosis. Here we reported that the missing transcriptional component was present within the metabolic active tissues in the lung of patients with sputum culture-negative tuberculosis, within which increased levels of circulating immune complexes and anti-dsDNA antibodies were found relative to nearby non-metabolic active tissues. Histological examination revealed specific vascular deposition of immune complexes, neutrophil extracellular traps, and vascular necrosis in the metabolic-active tissue. Thus, tuberculosis-initiated metabolic activity was associated with hyperactive antibody responses and vascular pathology, and shared features with systemic lupus erythematosus and other autoimmune diseases. We discussed these observations in the context of earlier literatures demonstrating that similar effects could be induced in humans and animal models by complete freund’s adjuvant, the most potent antibody response inducer ever reported. Our small case series, if verified in a larger size study, might help inform host-directed therapies to alleviate disease progression and augment treatment efficacy.

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“…Recent reports showed that ANCA antibodies are not only a biomarker of AAV but are involved in the pathogenesis of the renal involvement in AAV. Binding of MPO or proteinase 3 antibodies to autoantigens activates neutrophils, that degranulate and release reactive oxygen species [11]. Neutrophil extracellular traps (NETs) are released to contain infections, but if they are not properly regulated, they damage the endothelium and activate complement, thus provoking inflammation and microvascular thrombosis, explained as ANCA-cytokine sequence theory [12], [13].…”

Section: Discussionmentioning

confidence: 99%

Patient with Antineutrophil Cytoplasmic Antibody Associated Small Vessel Vasculitis, Acute Renal Failure, and Coronavirus Disease-19 Pneumonia: A Diagnostic and Therapeutic Challenge

Gerasimovska-Kitanovska

Selim

Petronijevik

et al. 2020

Open Access Maced J Med Sci

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BACKGROUND: Antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) has a predilection for the kidney and more than three quarters of patients have renal involvement with rapidly progressive glomerulonephritis. Small-vessel systemic vasculitis may present as pulmonary-renal syndrome and is characterized by necrotizing glomerulonephritis and pulmonary hemorrhage. Diagnosis and therapy for AAV in coronavirus disease (COVID) COVID-19 pandemic require multi-disciplinary collaboration due to the affection of multiple systems and risks associated with immunosuppressive medications. CASE REPORT: A 69-year-old non-smoker, non-diabetic female presented in the outpatient unit at the department of pulmonology with dry cough, malaise, and sub-febrile temperature, lasting for 1 month. The patient had a high suspicion of severe pulmonary-renal syndrome, ANCA-AAV, and acute renal failure requiring hemodialysis. She was treated with corticosteroids, cyclophosphamide, and plasma exchange. The treatment led to temporary improvement. Infections with COVID-19, Enterococcus in the urine, and Acinetobacter in the tracheal aspirate further complicated the clinical picture and despite antibiotic treatment, use of tocilizumab and convalescent plasma, the outcome was lethal. CONCLUSION: It is important to establish the diagnosis and distinguish accurately between vasculitis and infection to provide adequate and timely therapy.

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Formation and Disordered Degradation of Neutrophil Extracellular Traps in Necrotizing Lesions of Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis

Cited by 25 publications

References 25 publications

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis

Immune deposit and vasculopathy in metabolic-active lung tissues of patients with pulmonary tuberculosis

Patient with Antineutrophil Cytoplasmic Antibody Associated Small Vessel Vasculitis, Acute Renal Failure, and Coronavirus Disease-19 Pneumonia: A Diagnostic and Therapeutic Challenge

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