Induction of neutrophil responsiveness to myeloperoxidase antibodies by their exposure to supernatant of degranulated autologous neutrophils

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2822-2827 ◽  
Author(s):  
Christoph Hess ◽  
Salima Sadallah ◽  
Jürg-Alfred Schifferli
Keyword(s):  
Monoclonal Antibody ◽  
Cell Surface ◽  
Oxygen Radicals ◽  
Disease Process ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Polymorphonuclear Neutrophils ◽  
Proteinase 3 ◽  
Clinical Expression ◽  
Anca Vasculitis ◽  
Anca Associated Vasculitis

Antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) are the predominant autoantibodies present in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Their binding to the corresponding antigen on the surface of polymorphonuclear neutrophils (PMNs) is believed to trigger the disease process. Cytokines released during an inflammatory reaction are thought to prime resting PMNs, making them responsive to autoantibodies. In the present study we found that MPO but not PR3 could be detected on the cell surface of unstimulated PMNs after incubation with the supernatants of activated autologous PMNs. MPO was shown to be acquired from these supernatants, because PMNs did not express MPO when the supernatants were specifically MPO-depleted. In addition, purified soluble MPO bound to unstimulated PMNs. Unstimulated PMNs that had passively acquired MPO released oxygen radicals when incubated with monoclonal antibody anti-MPO or the immunoglobulin G fraction of a patient with MPO-ANCA. The data presented here suggest that, in ANCA-associated vasculitis, soluble MPO released by activated PMNs may bind to unstimulated PMNs, thereby making them reactive to anti-MPO antibodies. This mechanism of dispersing PMN activation would be specific for MPO-ANCA and may explain differences in the pathologic and clinical expression of MPO-ANCA versus PR3-ANCA vasculitis.

Induction of neutrophil responsiveness to myeloperoxidase antibodies by their exposure to supernatant of degranulated autologous neutrophils

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2822-2827 ◽  
Author(s):  
Christoph Hess ◽  
Salima Sadallah ◽  
Jürg-Alfred Schifferli
Keyword(s):  
Monoclonal Antibody ◽  
Cell Surface ◽  
Oxygen Radicals ◽  
Disease Process ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Polymorphonuclear Neutrophils ◽  
Proteinase 3 ◽  
Clinical Expression ◽  
Anca Vasculitis ◽  
Anca Associated Vasculitis

Abstract Antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) are the predominant autoantibodies present in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Their binding to the corresponding antigen on the surface of polymorphonuclear neutrophils (PMNs) is believed to trigger the disease process. Cytokines released during an inflammatory reaction are thought to prime resting PMNs, making them responsive to autoantibodies. In the present study we found that MPO but not PR3 could be detected on the cell surface of unstimulated PMNs after incubation with the supernatants of activated autologous PMNs. MPO was shown to be acquired from these supernatants, because PMNs did not express MPO when the supernatants were specifically MPO-depleted. In addition, purified soluble MPO bound to unstimulated PMNs. Unstimulated PMNs that had passively acquired MPO released oxygen radicals when incubated with monoclonal antibody anti-MPO or the immunoglobulin G fraction of a patient with MPO-ANCA. The data presented here suggest that, in ANCA-associated vasculitis, soluble MPO released by activated PMNs may bind to unstimulated PMNs, thereby making them reactive to anti-MPO antibodies. This mechanism of dispersing PMN activation would be specific for MPO-ANCA and may explain differences in the pathologic and clinical expression of MPO-ANCA versus PR3-ANCA vasculitis.

scholarly journals For fulminant rapidly progressive glomerulonephritis in a 17-year-old female patient with ANCA-associated vasculitis.

2018 ◽  
Vol 96 (2) ◽  
pp. 180-185
Author(s):  
Nadezhda B. Gordovskaya ◽  
E. M. Shilov ◽  
Yu. V. Korotchaeva ◽  
E. V. Stavrovskaya ◽  
S. V. Roshchupkin
Keyword(s):  
Renal Failure ◽  
Kidney Transplantation ◽  
Rapidly Progressive Glomerulonephritis ◽  
Proteinase 3 ◽  
Substitution Therapy ◽  
Anca Vasculitis ◽  
Terminal Renal Failure ◽  
Anca Associated Vasculitis ◽  
Morphological Picture ◽  
Systemic Manifestations

A case of rapidly progressive glomerulonephritis in a 17-year-old patient associated with antibodies against the cytoplasm of neutrophils (ANCA) vasculitis - ANCA-associated vasculitis is associated with antibodies to proteinase-3 and morphological picture extracapillar glomerulonephritis with sclerotic lesion of up to 80% of the glomeruli. The peculiarity of the case is the presence of morphologically confirmed when alloimmune rapidly progressive glomerulonephritis type III a pronounced glow-focal granular nature of immunoglobulin classes G and M on the basement membrane of capillaries. The appointment of immunosuppressive therapy led to a decrease in systemic manifestations of vasculitis, but there was a rapid increase in terminal renal failure, which required substitution therapy with hemodialysis. The possible mechanisms of the rapid-training course of the disease in the observed patient, prospects for kidney transplantation are discussed.

scholarly journals A Rare Case of Digital Ischemia and Gangrene in ANCA-Associated Vasculitis with Review of the Literature

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Richard A. Lau ◽  
Ramandeep Bains ◽  
Duminda Suraweera ◽  
Jane Ma ◽  
Emil R. Heinze ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
English Literature ◽  
Renal Involvement ◽  
Antineutrophil Cytoplasmic Antibody ◽  
High Dose ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Proteinase 3 ◽  
Anca Associated Vasculitis ◽  
Digital Ischemia

This paper describes one patient with Antineutrophil Cytoplasmic Antibody- (ANCA-) associated vasculitis who initially presented with multiple ischemic fingers and toes. On further evaluation, the patient was also found to have pulmonary-renal involvement and episcleritis. The diagnosis was supported with a positive cANCA (anti-proteinase 3) and a bronchoscopy consistent with diffuse alveolar hemorrhage. Although the patient refused a tissue biopsy, clinical presentation including nasal ulceration, sinus congestion, and epistaxis and anti-proteinase 3 antibody were more consistent with Granulomatosis with Polyangiitis (GPA) rather than Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on the recently presented ACR/EULAR Provisional 2017 Classification Criteria for GPA (Luqmani et al., 2016). The patient responded well to therapy including high dose steroids and cyclophosphamide, with improvement of all organs involved and had no further digital ischemia or gangrene on follow-up. We include a review of the English literature summarizing presentation, management, and outcome of 16 similar cases.

scholarly journals Catalytic Activity and Inhibition of Wegener Antigen Proteinase 3 on the Cell Surface of Human Polymorphonuclear Neutrophils

2009 ◽  
Vol 284 (30) ◽  
pp. 19896-19902 ◽  
Author(s):  
Brice Korkmaz ◽  
Jérôme Jaillet ◽  
Marie-Lise Jourdan ◽  
Alexandre Gauthier ◽  
Francis Gauthier ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Cell Surface ◽  
Polymorphonuclear Neutrophils ◽  
Proteinase 3

scholarly journals A Rare Case of Cholangiocarcinoma Complicating C-Anca Vasculitis

2020 ◽  
Vol 2 (5) ◽  
Author(s):  
Ferjaoui Wael ◽  
Keyword(s):  
Renal Failure ◽  
Hilar Cholangiocarcinoma ◽  
Rare Case ◽  
Locally Advanced ◽  
Autoimmune Disorder ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Pulmonary Involvement ◽  
Anca Vasculitis ◽  
Anca Associated Vasculitis

Antineutrophil cytoplasmic antibody (ANCA) - associated vasculitis is a severe autoimmune disorder. Its prognosis has been markedly improved by the introduction of immunosuppressive treatments. Nevertheless, this has been associated with an increased incidence of malignancy. We report the case of a 60-year-old woman who presented C-ANCA vasculitis with renal failure and pulmonary involvement requiring immunosuppressive therapy. A complete remission was achieved. After a follow-up of 22 months, she presented asthenia with fever and jaundice. The diagnosis of locally advanced peri-hilar cholangiocarcinoma was made. The outcome was unfavorable and the patient died. The incidence of malignancies is increased in ANCA vasculitis. Biliary tumors are uncommon compared to other cancers. The risk is mainly related to exposure to cyclophosphamide.

Saint John on Patmos: Revelations of the Role of Antineutrophil Cytoplasmic Antibody (ANCA) in Vasculitis

2020 ◽  
Vol 27 (17) ◽  
pp. 2852-2862
Author(s):  
Esther N. Pijnappel ◽  
Ger T. Rijkers ◽  
Frans J. van Overveld
Keyword(s):  
Cell Surface ◽  
Serine Protease ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Neutrophil Adhesion ◽  
Proteinase 3 ◽  
Serological Testing ◽  
Saint John ◽  
The Moment

Diagnosis of vasculitis is based on the presence of histologic features and serological testing for antineutrophil cytoplasmic antibodies (ANCA). In patients with vasculitis, two types of ANCA have been identified: ANCA directed against the neutrophil serine protease proteinase-3 (PR3) which results in a cytoplasmic immunofluorescence pattern (c-ANCA) and ANCA directed against the neutrophil enzyme myeloperoxidase (MPO), which results in a perinuclear immunofluorescence pattern (p-ANCA). Question is if the presence of ANCA is the consequence of abnormal neutrophil adhesion, activation, and apoptosis. Or is it, through mechanisms which are not totally clear for the moment, the cause of vasculitis. In the latter case it has to be postulated that ANCA autoantigens are expressed on the cell surface of viable, or activated, or early-apoptotic neutrophils.

A Population-based Study Showing Better Renal Prognosis for Proteinase 3 Antineutrophil Cytoplasmic Antibody (ANCA)–associated Nephritis Versus Myeloperoxidase ANCA–associated Nephritis

2014 ◽  
Vol 41 (7) ◽  
pp. 1366-1373 ◽  
Author(s):  
Aladdin J. Mohammad ◽  
Mårten Segelmark
Keyword(s):  
Patient Survival ◽  
Search Algorithm ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Population Based ◽  
Renal Outcome ◽  
Proteinase 3 ◽  
Endstage Renal Disease ◽  
Population Based Study ◽  
Anca Associated Vasculitis ◽  
Renal Prognosis

Objective.Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is usually differentiated based on clinical phenotypes, but recent data indicate that myeloperoxidase (MPO)-AAV is genetically distinct from proteinase 3 (PR3)-AAV. We reviewed a population-based cohort of AAV, focusing on differences in clinical and laboratory characteristics and to compare renal outcome between MPO-ANCA and PR3-ANCA nephritis.Methods.All new cases of AAV diagnosed between 1997 and 2009 in a geographically defined area in southern Sweden were retrieved using a validated search algorithm. Data were collected from time of diagnosis and end of followup. Renal and patient survival were analyzed according to ANCA serotype.Results.During the study period, 201 patients were diagnosed with AAV, 98 tested positive for PR3-ANCA, and 85 for MPO-ANCA. Patients with PR3-ANCA were younger, had significantly higher inflammatory activity, and had a larger number of organs involved at diagnosis, but nephritis was more prevalent among patients with MPO-associated (72/85; 85%) versus PR3-associated disease (67/98, 68%). When comparing only patients with ANCA-associated nephritis, those with MPO-ANCA were more likely to develop endstage renal disease (n = 27, 38%) than those with PR3-ANCA (n = 10, 15%), p = 0.003. The risk remained significantly elevated after adjusting for sex, age, and s-creatinine level at diagnosis (HR 2.64; 95% CI 1.25–5.58; p = 0.003). There were no significant differences in mortality rates between the 2 groups.Conclusion.The outcome in this population-based cohort indicates that among AAV patients with nephritis, renal prognosis is better in the PR3-ANCA group, even after adjustment for sex, age, and renal function at diagnosis.

scholarly journals The role of surgery in antineutrophil cytoplasmic antibody–associated vasculitides affecting the nose and sinuses: A systematic review

2020 ◽  
Vol 8 ◽  
pp. 205031212093673
Author(s):  
Alfonso Luca Pendolino ◽  
Samit Unadkat ◽  
Henry Zhang ◽  
Monica Pendolino ◽  
Gerolamo Bianchi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Symptom Relief ◽  
Disease Process ◽  
Active Phase ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Nasal Reconstruction ◽  
Medline Search ◽  
Throat Region ◽  
Anca Associated Vasculitis ◽  
Nose And Throat

Background: The ear, nose and throat region has been reported to be one of the commonest sites involved in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis diseases and often precedes the diagnosis of ANCA–associated vasculitis by many months. Although treatment for ANCA–associated vasculitis primarily requires systemic immunosuppressive therapy, there are specific indications for sinonasal surgery during the course of the disease process. The three major roles for surgery in sinonasal vasculitis are to aid diagnosis through biopsy, enable symptom relief and nasal reconstructive surgery consideration when in remission. Purpose: The aim of this systematic review is to provide an overview of the surgical procedures which can be performed in patients with ANCA–associated vasculitis presenting with sinonasal involvement. Materials and methods: A systematic literature search was performed for scientific articles on MEDLINE (PubMed Advanced MEDLINE Search) and EMBASE. The search included all articles up to April 2020. Conclusion: Surgical intervention during the active phase of ANCA–associated vasculitis disease can improve the patient’s symptoms and enable histological diagnosis. The surgical decision to manage the nose requires a multidisciplinary approach involving the vasculitis specialist and the ear, nose and throat surgeon. Nasal reconstruction can be performed to restore form and function but only when the disease is in remission so as to maximise success and minimise complications.

scholarly journals Proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitic neuropathy in diffuse cutaneous systemic sclerosis: a rare duo

2019 ◽  
Vol 12 (11) ◽  
pp. e232987 ◽  
Author(s):  
Yasser Radwan ◽  
Sarah Berini ◽  
Floranne Ernste ◽  
Ashima Makol
Keyword(s):  
Systemic Sclerosis ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Proteinase 3 ◽  
Vasculitic Neuropathy ◽  
Anca Associated Vasculitis ◽  
Common Clinical Presentation ◽  
Risk Of Disease ◽  
Diffuse Cutaneous Systemic Sclerosis

Systemic sclerosis (SSc) is characterised by non-inflammatory vasculopathy, autoimmunity and widespread fibrosis. While the presence of antineutrophil cytoplasmic antibodies (ANCAs) has been reported in SSc, their association with ANCA-associated vasculitis is exceedingly rare. Myeloperoxidase ANCA is more common than proteinase-3 ANCA, and glomerulonephritis is the most common clinical presentation of ANCA-associated vasculitis in SSc. ANCAs have been associated with the adverse disease outcomes in SSc, including higher mortality per recent reports. A 65-year-old man with diffuse cutaneous SSc for 6 years presented with new-onset peripheral neuropathy. Workup revealed a positive proteinase-3 and cytoplasmic ANCA, and histopathology confirmed an inflammatory vasculitic neuropathy. The patient was successfully treated with rituximab. Our case highlights the importance of checking ANCA in SSc at baseline, given the risk of disease-related complications, even years later. Tissue biopsy is often warranted for confirmation of vasculitis and prompt treatment can optimise long-term outcomes.

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