Pathogenesis and pathology of anti-neutrophil cytoplasmic antibody（ANCA）-associated vasculitis

Tsukui, Daisuke; Kimura, Yoshitaka; Kono, Hajime

doi:10.1016/j.jtauto.2021.100094

Cited by 5 publications

(3 citation statements)

References 116 publications

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“…Studies reported a pivotal and interconnected role for neutrophils and monocytes/macrophages in the acute phase of the disease [ 26 , 27 ]. ANCA-activated neutrophils cause vascular injury through the release of radical oxygen species and lytic enzymes [ 28 , 29 , 30 ], and macrophages that accumulate in focal areas of the glomerular tuft along the GBM by releasing matrix metalloproteinase-12 cause the rupture of the GBM [ 23 , 27 , 31 ]. Serine proteases such as catepsin G, proteinase-3 and elastase, released by activated neutrophils, are also able to induce a local activation of the renin angiotensin system by cleaving angiotensinogen to Ang I and further to Ang II at the site of injury and inflammation [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Add-On Cyclic Angiotensin-(1-7) with Cyclophosphamide Arrests Progressive Kidney Disease in Rats with ANCA Associated Glomerulonephritis

Cerullo

Rottoli

Corna

et al. 2022

Cells

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Rapidly progressive crescentic glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA-GN) is a major cause of renal failure. Current immunosuppressive therapies are associated with severe side effects, intensifying the need for new therapeutic strategies. The activation of Mas receptor/Angiotensin-(1-7) axis exerted renoprotection in chronic kidney disease. Here, we investigated the effect of adding the lanthionine-stabilized cyclic form of angiotensin-1-7 [cAng-(1-7)] to cyclophosphamide in a rat model of ANCA-GN. At the onset of proteinuria, Wistar Kyoto rats with ANCA-GN received vehicle or a single bolus of cyclophosphamide, with or without daily cAng-(1-7). Treatment with cAng-(1-7) plus cyclophosphamide reduced proteinuria by 85% vs. vehicle, and by 60% vs. cyclophosphamide, and dramatically limited glomerular crescents to less than 10%. The addition of cAng-(1-7) to cyclophosphamide protected against glomerular inflammation and endothelial rarefaction and restored the normal distribution of parietal epithelial cells. Ultrastructural analysis revealed a preserved GBM, glomerular endothelium and podocyte structure, demonstrating that combination therapy provided an additional layer of renoprotection. This study demonstrates that adding cAng-(1-7) to a partially effective dose of cyclophosphamide arrests the progression of renal disease in rats with ANCA-GN, suggesting that cAng-(1-7) could be a novel clinical approach for sparing immunosuppressants.

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Section: Discussionmentioning

confidence: 99%

Add-On Cyclic Angiotensin-(1-7) with Cyclophosphamide Arrests Progressive Kidney Disease in Rats with ANCA Associated Glomerulonephritis

Cerullo

Rottoli

Corna

et al. 2022

Cells

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“…The production of NETs also leads to damage of endothelial cells and may participate in activation of the alternative complement pathway. 33 , 34 …”

Section: Pathogenesismentioning

confidence: 99%

ANCA Associated Vasculitis Subtypes: Recent Insights and Future Perspectives

Austin¹,

Janagan²,

Wells³

et al. 2022

JIR

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The ANCA associated vasculitides (AAVs) affect a range of internal organs including ear nose and throat, respiratory tract, kidneys, skin and nervous system. They include granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA). The AAVs are treated with high dose glucocorticoids, immunosuppressants, and targeted biological medications. Since the 1990s classification criteria for the AAVs have been based on clinical features, laboratory tests and basic imaging; an initiative to update the classification criteria incorporating newer tests, for example, anti-neutrophil cytoplasmic antibodies (ANCA) and novel imaging techniques will be published this year. There is also evidence for classification of patients based on ANCA subtype; those with anti-proteinase 3 antibodies (PR3) or anti-myeloperoxidase antibodies (MPO) have differences in response to treatment and clinical outcomes. An update is described within this review. The pathogenesis of AAV involves necrotizing inflammation of small to medium blood vessels involving multiple immunological pathways. We present an update on emerging evidence related to auto-antibodies, complement and lymphocyte pathways. This review describes emerging treatment regimens, including evidence for plasma exchange in severe disease and the inhibitor of the complement C5a receptor (C5aR) inhibitor, Avacopan. Lastly, patient reported outcomes are key secondary outcomes in randomised controlled trials and increasingly clinical practice, we report development in disease specific and glucocorticoid-specific PROs.

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“…This term is often used to describe medium-and small-vessel disease (i.e., capillaries, venules, arterioles, and small arteries). It differentiates vasculitis occurring de novo from secondary vasculitis connected to infections, connective-tissue diseases or some types of malignancy [1]. AAV is a group of diseases, which clinically involves many organ systems, including the upperand lower-respiratory tracts, kidneys, skin, and nerves [2].…”

Section: Introductionmentioning

confidence: 99%

The Role of Neutrophils in ANCA-Associated Vasculitis: The Pathogenic Role and Diagnostic Utility of Autoantibodies

Walulik,

Łysak,

Błaszkiewicz

et al. 2023

IJMS

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Recent years have brought progress in understanding the role of the neutrophil, dispelling the dogma of homogeneous cells mainly involved in the prime defence against pathogens, shedding light on their pathogenic role in inflammatory diseases and on the importance of antineutrophil-cytoplasmic antibodies’ pathogenic role in ANCA-associated vasculitides vasculitis (AAV). Myeloperoxidase (MPO) and proteinase 3 (PR3) expressed in neutrophil granulocytes are the most common targets for ANCAs and contribute to the formation of MPO-ANCAs and PR3-ANCAs which, released to the bloodstream, become an excellent diagnostic tool for AAV. In this study, we focus on increasing the clinical and experimental evidence that supports the pathogenic role of ANCAs in AAV. Additionally, we discuss the diagnostic utility of ANCAs for disease activity and prognosis in AAV. Understanding the central role of ANCAs in AAV is crucial for advancing our knowledge of these complex disorders and developing targeted therapeutic strategies in the era of personalized medicine.

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Pathogenesis and pathology of anti-neutrophil cytoplasmic antibody（ANCA）-associated vasculitis

Cited by 5 publications

References 116 publications

Add-On Cyclic Angiotensin-(1-7) with Cyclophosphamide Arrests Progressive Kidney Disease in Rats with ANCA Associated Glomerulonephritis

Add-On Cyclic Angiotensin-(1-7) with Cyclophosphamide Arrests Progressive Kidney Disease in Rats with ANCA Associated Glomerulonephritis

ANCA Associated Vasculitis Subtypes: Recent Insights and Future Perspectives

The Role of Neutrophils in ANCA-Associated Vasculitis: The Pathogenic Role and Diagnostic Utility of Autoantibodies

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