Complement alternative pathway in ANCA-associated vasculitis: Two decades from bench to bedside

Publication date: Available online 15 November 2019Source: Autoimmunity ReviewsAuthor(s): Benoit Brilland, Anne-Sophie Garnier, Alain Chevailler, Pascale Jeannin, Jean-François Subra, Jean-François AugustoAbstractAnti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitides (AAVs) are small vessel vasculitides involving predominantly ear-nose-throat, kidneys, lungs and nerves. AAVs are life-threatening diseases, especially in their most severe forms such as necrotizing crescentic glomerulonephritis (GN) and/or intra-alveolar hemorrhage.Unlike immune complex GN or anti-glomerular basement membrane GN, AAVs are classified as pauci-immune GN. However, based on recent insights from animal models, the view of AAVs as a complement-unrelated disease has been challenged. Indeed, complement activation, and especially complement alternative pathway (cAP) activation, has been shown to be determinant in AAV pathogenesis through C5a generation, a potent chemoattractant for neutrophils with priming capacities.Here, we review in vitro and in vivo data supporting the role of cAP in murine models and in human AAVs. These findings, together with the need to eradicate glucocorticoid toxicity, led to the development of an anti-C5aR molecule, CCX168, also known as avacopan. Its development and future opportunities are also discussed.
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research

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Conclusion: Type II (immune complex) CGN was most common type followed by type V (immune negative) and type III (pauci-immune) CGN. The crescentic GN had worse prognosis with>80% of patients progressed to ESRD within 3 month of time from onset of illness. Early diagnosis and treatment is associated with favourable outcome. PMID: 31793263 [PubMed - in process]
Source: Journal of the Association of Physicians of India - Category: General Medicine Tags: J Assoc Physicians India Source Type: research
The objective of this review is: 1) to describe the pathogenesis, clinical and histological features of the disease; 2) to characterize double-positive anti-GBM/ANCA patients; 3) to highlight the prognostic factors of renal and global survival, and 4) to focus on the treatment of anti-GBM disease. PMID: 31776042 [PubMed - as supplied by publisher]
Source: Revue de Medecine Interne - Category: Internal Medicine Tags: Rev Med Interne Source Type: research
Purpose of review Although uncommon, systemic vasculitis is one of the most severe extraglandular manifestations of primary Sjögren's syndrome (pSS) accounting for the increased morbidity and mortality of the disease. This review aims to describe major previous and recent reports regarding the clinical presentation, prognosis and treatment of systemic vasculitis associated with pSS. Recent findings Both older and recent pSS cohort studies performed over the past several and recent years, have clearly shown that cryoglobulinaemic vasculitis is the most frequent type of systemic vasculitis accompanying pSS. Antineu...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: VASCULITIS SYNDROMES: Edited by Hasan Yazici and Yusuf Yazici Source Type: research
CONCLUSIONS: NDRD is common in DM patients (39%), being primary glomerulonephritis the most frequent ethology. The absence of retinopathy and the presence of microhematuria are highly suggestive of NDRD. The use of our predictive model could facilitate the indication of performing a renal biopsy in DM patients. PMID: 31761446 [PubMed - as supplied by publisher]
Source: Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia - Category: Urology & Nephrology Tags: Nefrologia Source Type: research
Authors: Berti A, Boukhlal S, Groh M, Cornec D Abstract Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) usually occurs in patients with late-onset asthma and sustained peripheral blood eosinophilia and classically presents with a clinical multifaceted spectrum of manifestations, which may vary at the different stages of the natural history of the disease.Areas covered: We reviewed EGPA clinical presentation, focusing on clinical manifestations at three different phases of the disease: 1/before the development of overt vasculitis, 2/at vasculitis diagnosis and 3/during the long-term follow-up. An ...
Source: Expert Review of Clinical Immunology - Category: Allergy & Immunology Tags: Expert Rev Clin Immunol Source Type: research
Conclusion: Diagnostic process often relies on a combination of clinical and histologic findings, with open lung biopsy considered the gold standard for confirmation of pulmonary involvement. In half of the cases in our center the fiberoptic bronchoscopy with endobronchial biopsy or transbronchial lung biopsy is an alternative in establishing the diagnosis.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Interventional pulmonology Source Type: research
A 10-year-old previously healthy boy, hailing from an Indian village had a history of hematuria, proteinuria, and generalized swelling for 3  months. This was diagnosed as crescentic glomerulonephritis on renal biopsy, and the patient was started on steroids. He presented with hypotensive shock and respiratory distress after a massive episode of hemoptysis following recurrent episodes of hemoptysis of small amounts for a month prior to this episode. Evaluation for causes of recurrent hemoptysis such as tuberculosis and pulmonary vasculitis were inconclusive.
Source: The Journal of Pediatrics - Category: Pediatrics Authors: Tags: Insights and Images Source Type: research
Abstract Anti-glomerular basement membrane (GBM) disease is a rare autoimmune vasculitis characterised by antibodies directed against the non collagenous (NC1) domain of the α3 chain of type 4 collagen (α3(IV)NC1). Clinical features are typically of a rapidly progressive glomerulonephritis (RPGN) with or without pulmonary haemorrhage. Treatment aims to rapidly remove circulating autoantibodies with plasma exchange and prevent further antibody production and suppress inflammation using immunosuppression and corticosteroids. Retrospective studies have shown that this combination of treatment results in g...
Source: Presse Medicale - Category: General Medicine Authors: Tags: Presse Med Source Type: research
Rationale: Occasionally, tubulointerstitial lesions can be found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, significantly isolated tubulointerstitial nephritis (TIN) with germinal centers is rare. Patient concerns: A 17-year-old Chinese Han patient showed rapidly progressive glomerulonephritis, anuria, and serum creatinine of 19.4 mg/dL. Diagnosis: He had positive ANCA targeting myeloperoxidase (55.0 RU/mL). The renal biopsy showed crescent formation in 100% of glomeruli. Of special note, the glomerular crescents were surrounded by granulomatous inflammation, extensive t...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Rationale: Bevacizumab—an inhibitor of vascular endothelial growth factor—is effective against various advanced cancers. However, it is associated with the development of hypertension and high-grade proteinuria during thrombotic microangiopathy of the kidney. In addition, there are several reports of immunoglobulin A deposition in the glomeruli, but the etiology is unclear. Patient concerns: A 67-year-old Japanese man with metastatic rectal cancer underwent low anterior rectal resection, followed by treatment with bevacizumab and SOX (S-1 plus oxaliplatin). Six months later, the patient developed hematuria...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
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