Emerging concepts in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis

  title={Emerging concepts in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis},
  author={Shaun M Flint and Eoin F. McKinney and Kenneth G. C. Smith},
  journal={Current Opinion in Rheumatology},
Purpose of reviewAntineutrophil cytoplasmic antibodies (ANCAs) remain central to our current understanding of the pathogenesis of ANCA-associated vasculitis (AAV), and this review considers recent developments in the context of four key questions: are there targets for ANCA beyond myeloperoxidase (MPO) and proteinase 3 (PR3); are all ANCA pathogenic; how are ANCAs generated; and how do ANCA cause disease? Recent findingsB-cell epitope mapping raises the possibility that only a subset of ANCA… 

Immunopathogenesis of ANCA-Associated Vasculitis

The current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers are summarized and it is illustrated how the extending knowledge of the Immunopathogenesis will likely translate into development of a personalized medicine approach in the management of AN CA-associated Vasculitis.

Pathogenesis and therapeutic interventions for ANCA-associated vasculitis

Advances in the understanding of anti-neutrophil cytoplasmic antibody-associated vasculitis are described and promising new treatments that target B cells, T cells and cytokines are generated; potential novel approaches targeting additional cells or molecules are also discussed.

Presence of dual anti-MPO and anti-PR3 antibodies in Systemic Lupus Erythematosus/ANCA-Associated Vasculitis

This is the first report of a case of SLE/AAV involving AAV (necrotising pauci-immune GN) with both anti-MPO and anti-PR3 antibodies, reported in the literature as antimyeloperoxidase antibodies (MPO) rather than antiproteinase 3 (PR3) antibodies.

Neutrophils from ANCA-associated vasculitis patients show an increased capacity to activate the complement system via the alternative pathway after ANCA stimulation

This study shows that primed and ANCA-stimulated neutrophil from AAV patients have a greater ability to activate the alternative complement pathway compared to primed neutrophils from healthy controls, highlighting the therapeutic potential of C5a and other complement blockade.

Small Vessel Vasculitis - To ANCA and Beyond

Understanding of autoantibodies in small vessel vasculitis is transformed and quantifying of ANCA and antibodies to MPO or PR3 show they reflect disease activity poorly and cannot be used to predict relapses, either in those treated with traditional immunosuppressive drugs or with anti-B cell therapy rituximab.

The Presence of Anti-Lactoferrin Antibodies in a Subgroup of Eosinophilic Granulomatosis with Polyangiitis Patients and Their Possible Contribution to Enhancement of Neutrophil Extracellular Trap Formation

It is suggested that aLf enhance NET formation induced by PMA and are associated with disease activity of EGPA and the effect was abolished completely by absorption of the aLF.

Pathogenic Role of ANCA in Small Vessel Inflammation and Neutrophil Function

A vicious circle emerges as NETs endowed with ANCA targets promote ANCA generation, and multiple factors induce the generation of ANCA, which in turn have the ability to promote neutrophil activation and progression towards neutrophils extracellular trap (NET) development.

Granulomatosis with polyangiitis: update and key concepts

Key aspects of granulomatosis with polyangiitis are reviewed, including aspects such as epidemiology, pathophysiology, clinical manifestations, diagnosis and treatment, which are fundamental to the development of new therapies for disease management.

Renal Tissue miRNA Expression Profiles in ANCA-Associated Vasculitis—A Comparative Analysis

A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results.



[Antineutrophil cytoplasmic antibodies].

There is increasing evidence that myeloperoxidase-ANCA are directly involved in the pathogenesis of necrotizing vasculitis, and data seem to confirm the long-disputed pathogenic role of these antibodies.

Genetically distinct subsets within ANCA-associated vasculitis.

This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyang iitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature ofproteinase 3 ANCA -associated vasulitis.

Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies.

The findings suggest that stimulation of neutrophils by ANCA causes release of factors that activate complement via the alternative pathway, thus initiating an inflammatory amplification loop that mediates the severe necrotizing inflammation of ANCA disease.

Clinical interpretation of antineutrophil cytoplasmic antibodies: parvovirus B19 infection as a pitfall

PR3-ANCA and MPO-AN CA may occur transiently in patients with acute B19 infection or infectious mononucleosis, highlighting the importance of repeated antibody tests in oligosymptomatic clinical conditions in which systemic autoimmune disease is suspected.

Autoantibodies to hLAMP-2 in ANCA-negative pauci-immune focal necrotizing GN.

In patients with ANCA-negative piFNGN, autoantibodies to hLAMP-2 that bind native glomerular but not neutrophil hLamp-2 are identified, suggesting a role in pathogenesis.

Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice.

This animal model offers strong support for a direct pathogenic role for ANCA IgG in human glomerulonephritis and vasculitis as well as the pathogenic potential of antibodies alone.

Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis.

ANCA specificity independently predicts relapse among patients with AAV with renal disease, and classification and diagnostic systems that incorporate ANCA specificity provide a more useful tool than the clinical pathologic category alone for predicting relapse.

A novel autoantibody against moesin in the serum of patients with MPO-ANCA-associated vasculitis.

  • Koya SuzukiT. Nagao Kazuo Suzuki
  • Biology, Medicine
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2014
The anti-moesin autoantibody existed in the serum of patients with MPO-AAV and was associated with the production of inflammatory cytokines/chemokines targeting neutrophils with a cytoplasmic profile, which suggests that the anti- moesin AutoAntibody has the possibility to be a novel autoantIBody developing vasculitis via neutrophil and endothelial cell activation.

Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis

FimH-triggered autoimmunity to LAMP-2 provides a previously undescribed clinically relevant molecular mechanism for the development of pauci-immune FNGN.

Anti-Proteinase 3 Anti-Neutrophil Cytoplasm Autoantibodies Recapitulate Systemic Vasculitis in Mice with a Humanized Immune System

A model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury, and human IgG from patients with anti- PR3 autoantibodies is therefore pathogenic.