Recent pathogenetic advances in ANCA-associated vasculitis

Pendergraft, William F.; Nachman, Patrick H.

doi:10.1016/j.lpm.2015.04.007

Cited by 10 publications

(16 citation statements)

References 38 publications

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“…ANCA-associated vasculitides (AAV) are a group of systemic pauci-immune diseases, characterized by inflammatory necrosis of the small vessels (arterioles, capillaries and venules) and the presence of antineutrophil cytoplasmic antibodies (ANCA) [6][7][8][9][10][11]. There are four clinical and pathological phenotypes of AAV: granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), eosinophilic granulomatosis with polyangiitis (EGPA, also known as Churg-Strauss syndrome), microscopic polyangiitis (MPA) and, finally, renal limited vasculitis (RLV), also known as idiopathic rapidly progressive glomerulonephritis (RPGN) [9,11].…”

Section: Anca-associated Vasculitidesmentioning

confidence: 99%

“…ANCA are IgG autoantibodies directed against proteinase 3 (PR3-ANCA), expressed in neutrophil granules, and myeloperoxidase (MPO-ANCA), expressed in monocyte lysosomes. PR3 and MPO are also expressed in the neutrophil extracellular traps (NET), localized to inflammatory lesions within the affected organs [6][7][8][9][10][11]. Because of their immunofluorescence pattern, PR3-ANCA are also described as cytoplasmic ANCA (c-ANCA), whereas MPO-ANCA are referred to as perinuclear ANCA (p-ANCA) [5,[9][10][11].…”

Section: Ancamentioning

confidence: 99%

“…Indirect immunofluorescence and enzymelinked immunosorbent assay (ELISA) methods are used to detect ANCA in the serum of patients [9,11]. The type of ANCA (PR3-ANCA or MPO-ANCA) defines the serotype of the AAV [8,11]. There is a correlation between the serotype and the phenotype of AAV.…”

Section: Ancamentioning

confidence: 99%

“…However, autoantibodies against different antigenic targets, such as lysosomeassociated membrane protein-2 (LAMP-2), plasminogen, moesin, have been demonstrated recently, and they were related to different precipitating causes, as well as different disease presentation and severity. Specifically, anti-LAMP-2 antibodies have been found in most patients with RLV linked to E. coli urinary tract infection (UTI), suggesting that molecular mimicking mechanisms may be responsible for the formation of antibodies [6][7][8][9][10].…”

Section: Ancamentioning

confidence: 99%

“…That increased expression of PR3 on the monocyte cell surface causes macrophage activation, while binding of MPO-ANCA promotes the release of pro-inflammatory cytokines, such as IL-1β, IL-6 and IL-8. On the other side, increased PR3 expression on the neutrophil surface, in patients with GPA, promotes diminished macrophage phagocytosis of neutrophils that have undergone apoptosis, leading to uncontrolled necrosis and release of more antigens and pro-inflammatory cytokines, including IL-6, IL-8 and TNF-α, which further amplify the previous pathological immune mechanism [6][7][8][9][10][11].…”

Section: Pathogenesismentioning

confidence: 99%

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Biomarkers in Renal Vasculitis

Arseniou¹,

Stai²,

Stangou³

2019

Glomerulonephritis and Nephrotic Syndrome

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The use of biomarkers in glomerular diseases has been subject of investigation during the last decades, as it can provide worthwhile evidence in diagnosis, but also, it can guide treatment and give information about prognosis and response. Renal biopsy is still the compulsory technique to establish diagnosis, and also to offer information about the severity of renal damage. However, as an invasive method, it cannot be regularly performed during follow up, so the need to find and establish measurement of molecules, easily collected, which are associated with disease pathogenesis and predict renal function outcome seems very attractive to nephrologists. The renal complications of systemic vasculitis are very important for the outcome of the disease, and several substances and molecules, such as inflammatory cells, autoantibodies, cytokines, chemokines and growth factors are produced and may serve as biomarkers to provide useful information for diagnosis, follow up of the disease.

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Section: Anca-associated Vasculitidesmentioning

confidence: 99%

Section: Ancamentioning

confidence: 99%

Section: Ancamentioning

confidence: 99%

Section: Ancamentioning

confidence: 99%

Section: Pathogenesismentioning

confidence: 99%

See 3 more Smart Citations

Biomarkers in Renal Vasculitis

Arseniou¹,

Stai²,

Stangou³

2019

Glomerulonephritis and Nephrotic Syndrome

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Vasculitis update: pathogenesis and biomarkers

Brogan

Eleftheriou

2017

Pediatr Nephrol

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Better understanding of the pathogenesis and treatment of primary systemic vasculitides (PSV) has led to the development of many potentially clinically relevant biomarkers. Genome-wide association studies have highlighted that MHC class II polymorphisms may influence the development of particular anti-neutrophil cytoplasmic antibody (ANCA) serotypes, but not the clinical phenotype of ANCA-associated vasculitis (AAV). Although ANCAs are overall poor biomarkers of disease activity, they may be useful for the prediction of flares of renal and/or pulmonary vasculitis. Moreover, patients with proteinase 3 (PR3)-AAV may respond better to rituximab than cyclophosphamide. Newer biomarkers of renal vasculitis in AAV include urinary soluble CD163, and may in the future reduce the requirement for renal biopsy. Better understanding of dysregulated neutrophil activation in AAV has led to the identification of novel biomarkers including circulating microparticles, and neutrophil extracellular traps (NETs), although their clinical utility has not yet been realised. Studies examining endothelial injury and repair responses have additionally revealed indices that may have utility as disease activity and/or prognostic biomarkers. Last, next-generation sequencing technologies are revealing monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2), and are profoundly influencing the approach to the diagnosis and treatment of vasculitis in the young.

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Antineutrophil cytoplasmic antibodies and their relationship with disease activity and presence of staphylococcal superantigens in nasal swabs in patients having granulomatosis with polyangiitis: results of a study involving 115 patients from a single center

Fijołek¹,

Wiatr²,

Petroniec³

et al. 2019

Clin Rheumatol

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Objective Antineutrophil cytoplasmic antibodies (ANCAs) are considered a risk factor for granulomatosis with polyangiitis (GPA) exacerbation, especially when staphylococcal superantigens (SAgs) are present in nasal swabs. Their role in monitoring disease activity remains controversial. This study determined the relationship of ANCAs with disease activity and presence of SAgs in GPA patients. Methods Among a total of 115 GPA patients hospitalized in the period 2009-2016, we investigated the presence of SAgs and ANCA concentration. Blood samples and nasal swabs were taken at each visit (referred further to as episodes). Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). Results We analyzed 362 episodes. ANCAs were detected in 215 (59.4%), while SAgs were detected in 126 (34.8%) episodes. We found a significant correlation between the presence of ANCAs and disease activity (p = 0.0032), as well as between their level and GPA severity (r = 0.25363, p = 0.000001). We also determined that an ANCA values ≥ 138 Ru/ml were an indicator of active disease with high specificity and low sensitivity (84.4% and 37.3%, respectively). The relationship between ANCA presence and the presence of SAgs was not confirmed; however, when SAgs were analyzed based on the different types, ANCA levels were found to be significantly higher in the group with SAg type B (p = 0.031). Conclusions There was no detectable evidence for the association between ANCA level and the presence of SAgs. Although monitoring ANCA levels as a marker of disease activity may be clinically relevant, GPA management cannot proceed on the basis of ANCA levels alone. Key Points • ANCA concentration usually correlates with GPA activity, although in half of patients, ANCAs persist despite effective treatment and clinical remission. • ANCA values of 138 Ru/ml seem to be an indicator of active disease with high specificity, but low sensitivity. • Although there is a relevance for ANCA monitoring as a marker of disease activity, GPA management cannot be based on ANCA levels alone. • The suspected clinical correlation between ANCA formation and SAg presence in nasal swabs is not obvious and requires further investigations.

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Recent pathogenetic advances in ANCA-associated vasculitis

Cited by 10 publications

References 38 publications

Biomarkers in Renal Vasculitis

Biomarkers in Renal Vasculitis

Vasculitis update: pathogenesis and biomarkers

Antineutrophil cytoplasmic antibodies and their relationship with disease activity and presence of staphylococcal superantigens in nasal swabs in patients having granulomatosis with polyangiitis: results of a study involving 115 patients from a single center

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