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Nature Reviews. Disease Primers Aug 2020The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are... (Review)
Review
The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA or ANCA, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Diagnostic Imaging; Humans; Immunosuppressive Agents; Myeloblastin; Peroxidase; Prognosis; Risk Factors
PubMed: 32855422
DOI: 10.1038/s41572-020-0204-y -
Journal of Clinical Medicine Apr 2021Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of small vessel vasculitides characterized by granulomatous and neutrophilic... (Review)
Review
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of small vessel vasculitides characterized by granulomatous and neutrophilic tissue inflammation, often associated with the production of antibodies that target neutrophil antigens. The two major antigens targeted by ANCAs are leukocyte proteinase 3 (PR3) and myeloperoxidase (MPO). AAV can be classified into 3 categories based on patterns of clinical involvement: namely, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA). Clinically, AAV involves many organ systems including the lungs, kidneys, skin, and nervous system. The prognosis of AAV has improved dramatically due to advances in the understanding of its pathogenesis and treatment modalities. This review will highlight some of the recent updates in our understanding of the pathogenesis, clinical manifestations, and treatment options in patients with AAV focusing on kidney involvement.
PubMed: 33916214
DOI: 10.3390/jcm10071446 -
International Journal of Molecular... Oct 2020Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels.... (Review)
Review
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Humans; Microscopic Polyangiitis; Myeloblastin; Peroxidase; Prognosis; Serogroup
PubMed: 33023023
DOI: 10.3390/ijms21197319 -
European Journal of Rheumatology Jul 2022Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's...
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg - Strauss syndrome). Renal-limited AAV can be considered a fourth entity. Despite their rarity and still unknown cause(s), research into AAV has been very active over the past decades and has allowed for the development of new therapeutic regimens. The pathogenesis is a complex process of immune dysregulations with genetic and environmental influences. Recent genome-wide association studies have identified multiple genetic predisposing variants, especially at the major histocompatibility complex region. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) is well supported by several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) is not as strongly demonstrated. B cells likely play a major role in the pathogenesis because they produce ANCAs, as do neutrophil abnormalities, imbalances in T-cell subtypes, and/or cytokine - chemokine networks. The role of the alternative complement pathway was established more recently, and studies of the antagonist of human C5a receptor (avacopan) in AAV have just been completed, with promising results. The current standard management of severe AAV still consists of remission induction therapy with glucocorticoids combined with rituximab or, less often now, cyclophosphamide. Several studies showed that reduced-dose regimens of glucocorticoids are noninferior to the previously used heavier regimens, for therefore less cumulative exposure to glucocorticoids. Avacopan use may even lead to new steroid-free therapeutic approaches, at least for some selected patients. Several trials and studies have now shown the superiority of rituximab over azathioprine or methotrexate as maintenance therapy. However, the optimal dosing regimen and duration for maintenance remain to be better defined, at the individual patient level. Many changes have occurred in the standard of care for AAV over the past decades, and more are expected soon, including with use of avacopan, but also, likely, a few other agents under investigation or development.
Topics: Animals; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Churg-Strauss Syndrome; Genome-Wide Association Study; Granulomatosis with Polyangiitis; Humans; Remission Induction; Rituximab
PubMed: 35156630
DOI: 10.5152/eujrheum.2022.20248 -
Neurology and Therapy Mar 2022Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic disorder that frequently affects the peripheral nervous system and consists of three... (Review)
Review
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic disorder that frequently affects the peripheral nervous system and consists of three distinct conditions: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA, previously Wegener's granulomatosis), and eosinophilic granulomatosis with polyangiitis (EGPA, previously Churg-Strauss syndrome). The neuropathic features associated with this condition usually include mononeuritis multiplex, which reflects the locality of lesions. Findings suggestive of vasculitis are usually found in the epineurium and occur diffusely throughout the nerve trunk. Nerve fiber degeneration resulting from ischemia is sometimes focal or asymmetric and tends to become conspicuous at the middle portion of the nerve trunk. The attachment of neutrophils to endothelial cells in the epineurial vessels is frequently observed in patients with ANCA-associated vasculitis; neutrophils play an important role in vascular inflammation by binding of ANCA. The positivity rate of ANCA in EGPA is lower than that in MPA and GPA, and intravascular and tissue eosinophils appear to participate in neuropathy. Immunotherapy for ANCA-associated vasculitis involves the induction and maintenance of remission to prevent the relapse of the disease. A combination of glucocorticoids along with cyclophosphamide, rituximab, methotrexate, or mycophenolate mofetil is considered depending on the severity of the condition of the organ to induce remission. A combination of low-dose glucocorticoids and azathioprine, rituximab, methotrexate, or mycophenolate mofetil is recommended to maintain remission. The efficacy of anti-interleukin-5 therapy (i.e., mepolizumab) was demonstrated in the case of refractory or relapsing EGPA. Several other new agents, including avacopan, vilobelimab, and abatacept, are under development for the treatment of ANCA-associated vasculitis. Multidisciplinary approaches are required for the diagnosis and management of the disorder because of its systemic nature. Furthermore, active participation of neurologists is required because the associated neuropathic symptoms can significantly disrupt the day-to-day functioning and quality of life of patients with ANCA-associated vasculitis.
PubMed: 35044596
DOI: 10.1007/s40120-021-00315-7 -
Autoimmunity Reviews Jun 2021The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood... (Review)
Review
The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood vessels affected (Chapel Hill classification). In recent years, several drugs with well-characterized immunological targets have been tested in clinical trials in large vessel vasculitis and small vessel vasculitis. Such trials provide "reverse translational" or bedside to bench information about underlying pathogenic mechanisms. Therefore, the aim of this systematic literature review was to examine the evidence base for a more refined mechanistic immunological classification of vasculitis. A total of 40 studies (20 randomized controlled trials (RCTs), 16 prospective studies, 1 retrospective cohort study and 3 case series) were included for full qualitative assessment. RCTs concerning biologic therapy for large vessel vasculitis mainly supports interleukin 6 receptor inhibition (tocilizumab). RCTs concerning biologic therapy for granulomatosis with polyangiitis and microscopic polyangiitis mainly support anti-CD20 treatment (rituximab) and complement inhibition with a small molecule C5a receptor antagonist (avacopan) is an emerging treatment option. The biologic treatment of eosinophilic granulomatosis with polyangiitis is centered around interleukin 5 inhibition (mepolizumab). Studies on tumor necrosis factor alpha inhibition (adalimumab, infliximab, and etanercept) showed negative results in giant cell arteritis but some effect in Takayasu arteritis. Taken together, clinical studies with cytokine and cell specific drugs are dissecting the heterogeneous immunopathogenic mechanisms of vasculitis and support a mechanistic immunological classification. Especially, cytokine antagonism is pointing towards immunological distinctions between eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis/microscopic polyangiitis and differences between giant cell arteritis and Takayasu arteritis.
Topics: Churg-Strauss Syndrome; Etanercept; Giant Cell Arteritis; Granulomatosis with Polyangiitis; Humans; Microscopic Polyangiitis; Randomized Controlled Trials as Topic; Rituximab; Takayasu Arteritis
PubMed: 33872767
DOI: 10.1016/j.autrev.2021.102829 -
Yonsei Medical Journal Jan 2023Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises group of small vessel vasculitides, including granulomatosis with polyangiitis (GPA),... (Review)
Review
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises group of small vessel vasculitides, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In 2022, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) jointly proposed new classification criteria for AAV (the 2022 ACR/EULAR criteria). In this review, we briefly summarize the 2022 ACR/EULAR criteria for GPA, MPA, and EGPA, and introduce our clinical experience with applying them to patients who were previously diagnosed with AAV based on three criteria: firstly, the classification criteria for GPA and EGPA proposed by the ACR in 1990; secondly, the algorithm for the classification of AAV and polyarteritis nodosa proposed by the European Medicines Agency algorithm in 2007 (the 2007 EMA algorithm); and thirdly, the revised International Chapel Hill Consensus Conference nomenclature of vasculitides in 2012 (the 2012 CHCC definitions). We found that concordance rate was highest in patients with MPA (96.6%), followed by those with EGPA (86.3%) and GPA (73.8%). In addition, compared to previous criteria, we noted several issues of the undervalued or overvalued items in the 2022 ACR/EULAR criteria for classifying AAV and provided several suggestions. To increase the diagnostic accuracy and reduce the discordance rate among the new and previous criteria for AAV, we suggest that the previous criteria should be considered together with the 2022 ACR/EULAR criteria when applying the classification criteria for AAV to patients suspected of AAV.
Topics: Humans; United States; Granulomatosis with Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Churg-Strauss Syndrome; Rheumatology; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis
PubMed: 36579374
DOI: 10.3349/ymj.2022.0435 -
European Respiratory Review : An... Dec 2021Over the past three decades, an increasing number of publications have reported the association between interstitial lung disease (ILD) and anti-neutrophil cytoplasmic... (Review)
Review
Over the past three decades, an increasing number of publications have reported the association between interstitial lung disease (ILD) and anti-neutrophil cytoplasmic antibody (ANCA) or ANCA-associated vasculitis (AAV). With this increased awareness, we have reviewed the literature to date and provide an update in this narrative review. The vast majority of cases of ILD have been shown to be in the setting of positive anti-myeloperoxidase antibody and can be present in up to 45% of patients of microscopic polyangiitis, though cases of ILD associated with proteinase 3 ANCA have rarely been reported. Pulmonary fibrosis and ANCA positivity can occur with or without systemic involvement. The pathogenetic mechanisms establishing the relationship between ANCA and the development of pulmonary fibrosis remain unclear. Histologic and radiographic features of ANCA-ILD most commonly reveal usual interstitial pneumonia or non-specific interstitial pneumonia patterns, though other atypical features such as bronchiolitis have been described. ILD in the setting of AAV has been associated with worse outcomes, and thus early identification and treatment in these patients is appropriate. We advocate that ANCA antibody testing be performed as a baseline evaluation in patients presenting with idiopathic interstitial pneumonia. Suggested treatment of ANCA-ILD includes immunosuppression and/or antifibrotic agents, though supporting data and clinical trials to substantiate use of these therapies are needed.
Topics: Antibodies, Antineutrophil Cytoplasmic; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Peroxidase
PubMed: 34750115
DOI: 10.1183/16000617.0123-2021 -
Clinical and Experimental Rheumatology 2020Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of systemic vasculitides that predominantly affect small vessels, including... (Review)
Review
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of systemic vasculitides that predominantly affect small vessels, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Pulmonary involvement is frequently observed in AAV patients, with various possible phenotypes in the different diseases. In the last years, among the possible types of lung involvement, a growing interest has been addressed to the interstitial lung disease (ILD). Prevalence of ILD is higher in MPA than in GPA; in fact, ILD has been reported in up to 45% of MPA patients and in 23% of GPA. Anti-MPO antibodies are the main ANCA subtype associated to ILD, in about 46-71% of cases, while anti-PR3 antibodies are reported in 0-29% of patients. High resolution computed tomography (HRCT) frequently detects interstitial lung abnormalities in AAV, up to 66% of patients with MPA, even if with an unclear clinical relevance, specifically in asymptomatic patients. Ground glass opacities, mainly consistent with diffuse alveolar hemorrhage (DAH), are the most frequent finding in MPA patients, but reticulations, interlobular septal thickening and honeycombing are also reported. ILD significantly affects quality of life and survival, with mortality increased 2 to 4 times, particularly higher in MPA patients with pulmonary fibrosis. Currently, immunosuppressive therapy is considered also as a possible treatment of ILD. However, a careful evaluation of progression and severity of lung involvement, should guide the treatment decision in the single patient. In this review, we discuss the available evidence on clinical features, diagnostic work-up, prognosis and management of AAV-ILD.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Humans; Lung Diseases, Interstitial; Microscopic Polyangiitis; Quality of Life
PubMed: 32324122
DOI: No ID Found