Animal Models of ANCA Associated Vasculitis

Shochet, Lani; Holdsworth, Stephen R.; Kitching, A. Richard

doi:10.3389/fimmu.2020.00525

Cited by 45 publications

(33 citation statements)

References 165 publications

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“…Increased PRTN3 was shown to have a negative effect on the resolution of inflammation that causes immune system deregulation [15]. In a mouse study, ANCAs that target MPO were injected through IV and it triggered extra capillary glomerulonephritis [16]. Neutrophil apoptosis is necessary in the resolution of inflammation [17].…”

Section: Discussionmentioning

confidence: 99%

ALTERED MOLECULAR PATHWAYS OBSERVED IN NASO-OROPHARYNGEAL SAMPLES OF SARS-CoV-2 PATIENTS

Akgun

Sahin

et al. 2020

Preprint

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Section: Discussionmentioning

confidence: 99%

ALTERED MOLECULAR PATHWAYS OBSERVED IN NASO-OROPHARYNGEAL SAMPLES OF SARS-CoV-2 PATIENTS

Akgun

Sahin

et al. 2020

Preprint

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“…ANCA has been shown to induce neutrophil activation that leads to capillaritis manifestations in vitro ( 49 , 50 ). In some proposed animal models of PR3-ANCA disease, capillaritis also develops but convincing evidence of granulomatous inflammation has not been reported to date ( 51 – 53 ). The association of PR3-ANCA increase and subsequent relapse was consistent in all patients with capillaritis at disease presentation, regardless of treatment regimen received.…”

Section: Discussionmentioning

confidence: 99%

Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3 in ANCA-Associated Vasculitis

et al. 2020

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Background: The utility of ANCA testing as an indicator of disease activity in ANCA-associated vasculitis (AAV) remains controversial. This study aimed to determine the association of ANCA testing by various methods and subsequent remission and examine the utility of a widely used automated addressable laser-bead immunoassay (ALBIA) to predict disease relapses. Methods: Data from the Rituximab vs. Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used. ANCA testing was performed by direct ELISA, capture ELISA, and ALBIA. Cox proportional hazards regression models were used to evaluate the association of PR3-ANCA level and subsequent remission or relapse. The ALBIA results are routinely reported as >8 when the value is high. For this study, samples were further titrated. A decrease and increase in PR3-ANCA were defined as a halving or doubling in value, respectively. Results: A decrease in ANCA by ALBIA at 2 months was associated with shorter time to sustained remission (HR 4.52, p = 0.035). A decrease in ANCA by direct ELISA at 4 months was associated with decreased time to sustained remission (HR 1.77, p = 0.050). There were no other associations between ANCA decreases or negativity and time to remission. An increase in PR3-ANCA by ALBIA was found in 78 of 93 subjects (84%). Eleven (14%) had a PR3-ANCA value which required titration for detection of an increase. An increase of ANCA by ALBIA was associated with severe relapse across various subgroups. Thompson et al. Serial PR3-ANCA Measurement in AAV Conclusions: A decrease in ANCA by ALBIA at 2 months and by direct ELISA at 4 months may be predictive of subsequent remission. These results should be confirmed in a separate cohort with similarly protocolized sample and clinical data collection. A routinely used automated ALBIA for PR3-ANCA measurement is comparable to direct ELISA in predicting relapse in PR3-AAV. Without titration, 14% of the increases detected by ALBIA would have been missed. Titration is recommended when this assay is used for disease monitoring. The association of an increase in PR3-ANCA with the risk of subsequent relapse remains complex and is affected by disease phenotype and remission induction agent.

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“…Although the pathogenic role of anti-MPO ANCA has not been overtly demonstrated in EGPA, it is presumed that similar mechanisms to the ones known in MPA occur. Several animal models have demonstrated the direct noxious role of ANCA toward endothelial cells and their key interaction with neutrophils in vasculitis pathogenesis as the cause of necrotizing-crescentic glomerulonephritis (NCGN) and pulmonary hemorrhage ( 76 ). The pathogenic potential of MPO-ANCA has been documented either by injection of anti-MPO IgG in mice ( 77 ), by injection of splenocytes containing anti-MPO positive B-cells in Rag2 −/− mice (which lack B and T cell responses) ( 77 ) or by transplanting bone marrow that contain MPO-positive myeloid cells in irradiated MPO −/− mice previously immunized with MPO antigen ( 78 ).…”

Section: Egpa As a Vasculitic Disordermentioning

confidence: 99%

Eosinophilic Granulomatosis With Polyangiitis: Dissecting the Pathophysiology

2021

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Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystemic disease classified both amongst hypereosinophilic disorders and ANCA-associated vasculitis. Vessel inflammation and eosinophilic proliferation are the hallmarks of the disease and main effectors of organ damage. Two distinct disease phenotypes have classically been described according to ANCA-status: the ANCA-negative subset with eosinophil-driven manifestation and the ANCA-positive one with vasculitic manifestations. An analogous dichotomization has also been backed by histological findings and a distinct genetic background. EGPA is typically consider a Th2-mediated disease and blood and tissue eosinophilia represent the cornerstone of diagnosis. Besides, ANCA are known for inducing endothelial injury and vascular inflammation by activating the circulating neutrophils. Thus, the pathogenesis of EGPA seems to be mediated by two coexisting mechanisms. However, the verbatim application of this strict dualism cannot always be translated into routine clinical practice. In the present review we describe the current knowledge on the eosinophilic and ANCA-mediated aspects of EGPA pathogenesis. Finally, we review the rationale of the currently proposed EGPA dichotomy and future research perspectives.

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Animal Models of ANCA Associated Vasculitis

Cited by 45 publications

References 165 publications

ALTERED MOLECULAR PATHWAYS OBSERVED IN NASO-OROPHARYNGEAL SAMPLES OF SARS-CoV-2 PATIENTS

ALTERED MOLECULAR PATHWAYS OBSERVED IN NASO-OROPHARYNGEAL SAMPLES OF SARS-CoV-2 PATIENTS

Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3 in ANCA-Associated Vasculitis

Eosinophilic Granulomatosis With Polyangiitis: Dissecting the Pathophysiology

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