Neutrophils from ANCA-associated vasculitis patients show an increased capacity to activate the complement system via the alternative pathway after ANCA stimulation

Ohlsson, Sophie; Holm, Lisa; Hansson, Christina; Ohlsson, Susanne; Gunnarsson, Lena; Pettersson, Åsa; Skattum, Lillemor

doi:10.1371/journal.pone.0218272

Cited by 19 publications

(11 citation statements)

References 32 publications

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“…In addition to the functional consequences of genetic variation in PRTN3 and its inhibitor SERPINA1 (reF. 40 ) and epigenetically mediated increases in PR3 and MPO expression 47,102 , neutrophils from patients with AAV, even from those in remission, produce more intracellular reactive oxygen species, display greater NET release and have a greater capacity to active the alternative pathway of complement (see below) 103,104 . The relative contribution of neutrophil intrinsic properties versus their response to priming events is unclear but both are likely to be relevant.…”

Section: Neutrophil Priming and Activation State Althoughmentioning

confidence: 99%

ANCA-associated vasculitis

Kitching

Anders

Basu

et al. 2020

Nat Rev Dis Primers

591

507

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The anti-neutrophil cytoplasmic antibody (ANCA)associated vasculitides (AAVs) are diseases characterized by inflammation of blood vessels, endothelial injury and tissue damage. The three types of small-vessel vasculitis, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA; previously known as Churg-Strauss syndrome), feature a loss of tolerance to neutrophil primary granule proteins, most often leukocyte proteinase 3 (PR3; also known as myeloblastin) or myeloperoxidase (MPO) (Table 1). The vessels involved in AAV are typically capillaries, arterioles and venules but small arteries and veins may also be affected. Autoimmunity is documented clinically by serum ANCAs to PR3 (PR3-ANCA) or MPO (MPO-ANCA), which are generally associated with the main syndromic AAV presentations (box 1). AAVs collectively represent one of several types of autoimmune vasculitis (Fig. 1). GPA and MPA can involve small blood vessels in any organ or tissue but commonly affect the upper and lower respiratory tract and the kidneys (box 2). Patients with AAV typically present with severe organ-threatening or life-threatening disease, although less severe presentations also occur. GPA is predominantly associated with PR3-ANCA and its clinical features typically include sinonasal disease, lower respiratory tract involvement with pulmonary haemorrhage and granulomatous inflammation, and glomerulonephritis. MPA is usually associated with MPO-ANCA and clinical features include more severe renal disease and some of the manifestations of GPA but without granulomatous inflammation. EGPA is characterized by asthma, eosinophilia and, in many (but not all) cases, vasculitis. EGPA is less common than GPA or MPA and, in some cases, is associated with ANCAs, mainly MPO-ANCA (Table 1). Although categorized as a form of AAV, EGPA has less overlap with the other AAVs than that between GPA and MPA with regard to its genetic, pathogenetic, and clinical features and its management and is typically considered a separate entity. Improvements in treatment and prognosis for patients with AAV have resulted from the translation of both preclinical and clinical research findings. Here, we provide an updated overview of the clinical and

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Section: Neutrophil Priming and Activation State Althoughmentioning

confidence: 99%

ANCA-associated vasculitis

Kitching

Anders

Basu

et al. 2020

Nat Rev Dis Primers

591

507

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“…В той же работе было показано, что мембранные микрочастицы, образующиеся при активации НГ, также могут активировать альтернативный путь комплемента в сыворотке крови. Позже этот эффект был подтвержден при изучении активации комплемента у пациентов с ANCA-ассоциированным васкулитом [69]. При действии антител MPO-ANCA (к МПО) и PR3-ANCA (к протеиназе 3) на НГ пациентов с соответствующими болезнями НГ выделяли вещества неизвестной природы, способствовавшие активации комплемента, но такого эффекта не обнаружено при действии этих антител на нейтрофилы здоровых доноров [70].…”

Section: влияние тотального вещества гранул и фрагментов нейтрофильных гранулоцитов на систему комплементаunclassified

Antimicrobial proteins and peptides of neutrophilic granulocytes as modulators of complement system

Krenev¹,

Berlov²,

Umnyakova³

2021

Immunologiya

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Антимикробные белки и пептиды нейтрофильных гранулоцитов как модуляторы системы комплементаФедеральное государственное бюджетное научное учреждение «Институт экспериментальной медицины» Министерства науки и высшего образования Российской Федерации, 197376, г. Санкт-Петербург, Российская Федерация Резюме Нейтрофильные гранулоциты (нейтрофилы) и система комплемента -важные факторы врожденного иммунитета позвоночных. Вследствие длительной коэволюции между ними сформировались разнообразные отношения. Накоплены данные о действии антимикробных белков и пептидов нейтрофилов на комплемент. В данной работе кратко рассматривается биология нейтрофилов и комплемента, систематизируются работы, посвященные действию миелопероксидазы, активных форм кислорода, лизоцима, антимикробных пептидов, лактоферрина, нейтрофильных внеклеточных ловушек, фрагментов нейтрофилов и тотального вещества гранул на комплемент человека. Акцент делается на физиологической и патофизиологической роли такой модуляции.

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“…Although ANCAs may activate neutrophils without additional inflammatory signals, neutrophil priming by exogenous or endogenous proinflammatory signals promotes the damaging effects of these cells after ANCA-induced activation (Figures 3 and 4). In addition to the functional consequences of genetic variation in PRTN3 and its inhibitor SERPINA1 101 and epigenetically mediated increases in PR3 and MPO 46,102 , neutrophils from AAV patients, even in remission, produce more intracellular reactive oxygen species, NETs and have a greater capacity to active the alternative pathway of complement (see below) 103,104 . The precise contributions of intrinsic properties of neutrophils and their response to priming events are unclear, but both are likely to be relevant.…”

Section: [H3] Ancas Activate Neutrophils and Monocytesmentioning

confidence: 99%

ANCA-associated vasculitis

Jayne¹

2020

Oxford Textbook of Medicine

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The ANCA-associated vasculitides (AAV) are a grouping of three syndromes of acute and chronic inflammation characterized by their clinical and histological phenotypes, which are associated with circulating antineutrophil cytoplasm autoantibodies (ANCA). They comprise: granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis); microscopic polyangiitis (MPA); and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome). The defining histological lesion is a microscopic vasculitis affecting arterioles, capillaries, or venules associated with few or no deposits of immunoglobulin or complement. Granulomata, involving or close by blood vessels, are commonly present in GPA. These diseases involve multiple organ systems with considerable heterogeneity in extent and severity of organ involvement between patients, and overlapping clinical and histological features between syndromes.

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Neutrophils from ANCA-associated vasculitis patients show an increased capacity to activate the complement system via the alternative pathway after ANCA stimulation

Cited by 19 publications

References 32 publications

ANCA-associated vasculitis

ANCA-associated vasculitis

Antimicrobial proteins and peptides of neutrophilic granulocytes as modulators of complement system

ANCA-associated vasculitis

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