Crescentic glomerulonephritis & small vessel vasculitis

The antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) are a group of primary vasculitides that affect predominantly small- to medium-sized blood vessels. AAV include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Disease severity is dictated by the location and extent of the blood vessels affected. If left untreated, systemic forms of AAV are often fatal. The advent of immunosuppressive therapy (cyclophosphamide plus glucocorticoids) has revolutionised the prognosis for patients with AAV, transforming the course of the disease from fatal to one that can be managed, though not without significant treatment-related toxicity...

The classification of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has limitations because the condition includes disorders with similar general clinical features, similar characteristics of lung and renal involvement and a positive ANCA serology. A 40-year-old woman was admitted to our hospital for hemoptysis and dyspnea. She had no history of bronchial asthma. Laboratory examinations revealed hypereosinophilia, positive anti-myeloperoxidase antibodies, hematuria and proteinuria. The patient was ultimately diagnosed with AAV associated with diffuse alveolar hemorrhage, rapidly progressive glomerulonephritis and hypereosinophilia without bronchial asthma...

Antineutrophil cytoplasmic antibody-associated small-vessel vasculitides cause multiple organ system disease including rapidly progressive glomerulonephritis. Recently, Berden et al (J Am Soc Nephrol. 2010;21:1628-1636) proposed a new histopathologic classification scheme separating renal biopsies into 4 classes: focal, crescentic, mixed, and sclerotic. We validated the prognostic implications of this classification scheme in a retrospective cohort study of 67 individuals with antineutrophil cytoplasmic antibody glomerulonephritis who underwent kidney biopsy in Calgary, Alberta, between 2005 and 2010...

Granulomatosis with polyangiitis (GPA) is associated with a broad range of clinical manifestations including renal disease. It is a systemic vasculitis that is rarely encountered in children. We present a 14-year-old girl who suffered from pharyngitis 1 week before admittance to hospital. She was admitted for macroscopic hematuria and oliguria, under the possibility of nephritic syndrome. Renal failure with rapidly progressive glomerulonephritis occurred within 24 hours. Immunologic tests showed the presence of type-C anti-neutrophil cytoplasmic antibodies (c-ANCA with antiproteinase 3 specificity) and renal biopsy revealed pauci-immune crescentic focal necrotizing glomerulonephritis...

Rapidly progressive glomerulonephritis (RPGN) results from severe crescentic damage to glomeruli and leads to irreversible kidney failure if not diagnosed and managed in a timely fashion. Traditional treatment has relied on glucocorticoids and cyclophosphamide, with additional plasmapheresis for certain conditions. Here we describe updates in the management of RPGN, according to the underlying renal pathology. However, there remains a paucity of trials that have enrolled patients with more advanced renal disease, dialysis dependence or with RPGN, and we are therefore still reliant on extrapolation of data from studies of patients with a less severe form of disease...

OBJECTIVES: Pauci-immune glomerulonephritis is the commonest cause of rapidly progressive glomerulonephritis (RPGN) which is associated with increased mortality and morbidity. More than 90% of these patients have serological presence of either antineutrophil cytoplasmic antibodies (ANCA), of cytoplamic (C) or perinuclear (P) type. "Immunofluoresence studies" exhibiting minimal or no fluorescence is diagnostic in all such cases. The present study aims to study the differences between renal biopsies of serologically ANCA negative versus ANCA positive individuals...

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of pauci-immune small vessel vasculitides that often affect the kidneys manifesting as rapidly progressive glomerulonephritis. Although the exact pathogenesis of AAV is not fully known, evidence from in vitro, in vivo and clinical studies all point to the involvement of ANCA in the pathogenesis of AAV. In this review, we highlight the contributory roles played by various factors (e.g. genetics, environment, B and T-regulatory cells, toll-like receptors, etc...

This review provides a summary of recent advances in the understanding of crescentic glomerulonephritis, focusing on antineutrophil cytoplasm antibody (ANCA)-associated vasculitis and anti-glomerular basement membrane (anti-GBM) antibody disease. In ANCA-associated vasculitis (AAV), four main conceptual advances are discussed as follows: (1) evidence for the pathogenicity of ANCA, (2) molecular mimicry and the role of infection in AAV, (3) evidence for aberrant T-cell responses and T-cell regulation in AAV, and (4) advances in understanding of genetic predisposition to AAV...

One of the main characteristics of the vasculitis associated with antineutrophil cytoplasm autoantibodies (AASV) is the absence of immune complex deposition in biopsies of affected tissues as well as a lack of complement depletion. However, in early stages of disease induced in animal models, it has been observed that the complement system may be involved in the generation of these diseases. There are various animal models which have been developed with the aim of knowing which are the pathogenic mechanisms in granulomatosis with polyangiitis (Wegener) (GPA) and microscopic polyangiitis (MPA), the latter being explained using these approaches in a more satisfactory manner, as there is lack of a model which reproduces the changes leading to a granulomatous vasculitis associated with antibodies against proteinase-3, as in GPA...

OBJECTIVE: To compare the usefulness of 3 currently used classification systems in predicting the outcomes of treatment resistance, disease relapse, end-stage renal disease (ESRD), and death in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Three classification systems were applied to 502 patients with biopsy-proven AAV: 1) the Chapel Hill Consensus Conference (CHCC) definition with categories for granulomatosis with polyangiitis (GPA) (Wegener's), microscopic polyangiitis (MPA), and kidney-limited disease; 2) the European Medicines Agency (EMA) system with categories for GPA and MPA; and 3) classification based on ANCA with specificity for myeloperoxidase (MPO ANCA) versus ANCA with specificity for proteinase 3 (PR3 ANCA)...

Myeloperoxidase (MPO) is a target antigen for antineutrophil cytoplasmic autoantibodies (ANCA). There is evidence that MPO-ANCA cause necrotizing and crescentic glomerulonephritis (NCGN) and vasculitis. NCGN severity varies among patients with ANCA disease, and genetic factors influence disease severity. The role of genetics in MPO-ANCA NCGN severity was investigated using 13 inbred mouse strains, F1 and F2 hybrids, bone marrow chimeras, and neutrophil function assays. Mouse strains include founders of the Collaborative Cross...

BACKGROUND AND OBJECTIVES: The subclinical pathogenesis of granulomatosis with polyangiitis (GPA) has not been completely elucidated. Proteinase 3 (PR3) antibodies are strongly associated with GPA, but have not been evaluated before disease presentation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective case-control serum bank study in which PR3 antibodies and C-reactive protein (CRP) in up to three longitudinal serum samples for 27 GPA patients before diagnosis (1 day-19 years) were compared with 27 controls whose serum samples were matched for age, sex, and race...

Antineutrophil cytoplasmic autoantibody (ANCA)-associated diseases are small-vessel vasculitides, encompassing granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Once considered life-threatening diseases, the introduction of stage-adapted immunosuppressive therapy and medications with decreased toxicity has improved patients' survival. Treatment is biphasic, consisting of induction of remission (3-6 months) for rapid control of disease activity and maintenance of remission (at least 18 months) to prevent disease relapse using therapeutic alternatives that have reduced toxicity...

Granulomatosis with Polyangiitis (GPA, formerly known as Wegener) is a systemic vasculitis characterized by granulomatous involving upper and lower respiratory tract and can also cause necrotizing glomerulonephritis (Umemoto et al. 2012 and Takala et al. 2011). GPA is associated with antineutrophil cytoplasmic autoantibodies (ANCA) against serine proteinase 3 (PR3) (Takala et al. 2011, Dufour et al. 2012, and Berthoux et al. 2011). This disease usually starts with involvement of the upper and lower respiratory tracts and also can involve kidney, eyes, skin, central and peripheral nervous systems, and gastrointestinal tract (Umemoto et al...

Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized by systemic vasculitis. The disease predominantly affects small-calibre blood vessels and is associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCA). Microscopic polyangiitis was considered to be a disease entity by Savage et al. in 1985. Microscopic polyangiitis has a reported low incidence and a slight male predominance. The aetiology of MPA remains unknown. There is, however, increased evidence that MPA is an autoimmune disease in which ANCAs, particularly those reacting with MPO, are pathogenic...

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss, EGPA) is a systemic small-vessel vasculitis associated with asthma and eosinophilia. Histology of EGPA shows tissue eosinophilia, necrotizing vasculitis, and eosinophil-rich granulomatous inflammation. EGPA commonly presents with upper airway tract and lung involvement, peripheral neuropathy, cardiac and skin lesions. Antineutrophil cytoplasmic antibodies (ANCA) are positive in ~40% of the cases and more often in patients with clinical manifestations due to small-vessel vasculitis...

Necrotizing, small-vessel vasculitis develops in patients with circulating ANCAs. Neutrophils and monocytes harbor the two major ANCA antigens, PR3 and MPO. A whole body of in vitro experiments implicated ANCA-activated neutrophil effector functions in the pathogenesis of vasculitis, whereas the role of monocytes is less well-characterized. Mouse models for anti-MPO-induced vasculitis were developed to study ANCA-neutrophil interactions in complex in vivo situations. We not only discuss the significance of ANCA-neutrophil interactions for disease induction but also how a detailed understanding of these interactions helps to identify novel treatment targets for ANCA vasculitis...

BACKGROUND: Sub-acute bacterial endocarditis (SBE) rarely presents with features of a small vessel vasculitis. Patients with SBE can also develop multiple serological abnormalities including ANCA. In this report, we present a case of infective endocarditis mimicked ANCA associated glomerulonephritis. CASE PRESENTATION: A 57-year old male with a clinical picture of rapidly progressive renal failure (RPGN) and positive seology for PR3-ANCA (C-ANCA) was referred to our hospital...

B cells and their progeny that produce and release anti-neutrophil cytoplasmic autoantibodies (ANCA) are the primary cause for an aggressive form of necrotizing small vessel vasculitis. Cytoplasmic ANCA antigens are released at the surface and in the microenvironment of cytokine-primed neutrophils. Binding of ANCA to ANCA antigens activates neutrophils by both Fc receptor engagement and direct Fab'2 binding to antigen on the cell surface. ANCA-activated neutrophils release factors that induce alternative complement pathway activation, which establishes a potent inflammatory amplification loop that causes severe necrotizing vascular inflammation...

Granulomatosis with polyangiitis, formerly known as Wegener's granulomatosis or disease, is a systemic, necrotizing small-vessel vasculitis, belonging to the group of anti-neutrophil cytoplasm antibody vasculitis. The therapeutic strategy includes, in most cases, corticosteroids associated, at least in severe forms of the disease, with immunosuppressive agents: cyclophosphamide and rituximab to induce remission, methotrexate, azathioprine and mycophenolate mofetil to prevent relapses. Intravenous immunoglobulins represent an alternative adjuvant therapy...