Systemic Vasculitis Associated with Anti-Neutrophil Cytoplasmic Antibodies against Bactericidal/Permeability Increasing Protein

Fukuhara, Atsuro; Tanino, Yoshinori; Sato, Suguru; Ishii, Taeko; Nikaido, Takefumi; Kanazawa, Kenya; Saito, Junpei; Ishida, Takashi; Kanno, Makoto; Watanabe, Tsuyoshi; Munakata, Mitsuru

doi:10.2169/internalmedicine.52.9477

Cited by 10 publications

(5 citation statements)

References 19 publications

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“…In addition to MPO and PR3, several other neutrophil-derived molecules can be targeted by ANCAs, including α-enolase, azurocidin, bactericidal permeability-increasing protein (BPI), cathepsin G, elastase, defensin, lactoferrin, lysosome-associated membrane glycoprotein 2 (LAMP2), and moesin. [25][26][27][28][29][30][31][32] The pathogenicity of these 'minor' ANCAs is generally low, and p-ANCAs other than MPO-ANCA are not usually associated with vasculitis; however, discussion is ongoing as to whether some minor ANCAs might show pathogenic involvement in AAV. [25][26][27][28][29][30][31][32]…”

Section: [H2] Ancasmentioning

confidence: 99%

Pathogenesis and therapeutic interventions for ANCA-associated vasculitis

et al. 2018

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Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a vasculitis that affects systemic small vessels, accompanied by the presence of ANCAs in the serum. This disease entity includes microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and drug-induced AAV. Similar to other autoimmune diseases, AAV develops in patients with a predisposing genetic background who have been exposed to causative environmental factors. The mechanism by which ANCAs cause vasculitis involves ANCA-mediated excessive activation of neutrophils that subsequently release inflammatory cytokines, reactive oxygen species and lytic enzymes. In addition, this excessive activation of neutrophils by ANCAs induces formation of neutrophil extracellular traps (NETs). Although NETs are essential elements in the innate immunity, excessive NET formation is harmful to small vessels. Moreover, NETs are involved not only in ANCA-mediated vascular injury but also in the production of ANCAs themselves. Therefore, a vicious cycle of NET formation and ANCA production is considered to be involved in the pathogenesis of AAV.

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Section: [H2] Ancasmentioning

confidence: 99%

Pathogenesis and therapeutic interventions for ANCA-associated vasculitis

et al. 2018

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“…These include cathepsin G, lactoferrin, elastase, defensin, α-enolase, moesin, azurocidin, bactericidal-permeability-increasing protein (BPI) and lysosome-associated membrane glycoprotein 2 (LAMP2) [70][71][72]. The pathogenicity of these "minor" ANCAs is generally considered to be low, and p-ANCA patterns other than MPO-ANCA are typically not associated with vasculitis [73,74]. ANCA testing focuses on two main techniques: indirect immunofluorescence (IIF) on fixed neutrophils and specific PR3-and MPO-ANCA solidphase immunoassays [75,76].…”

Section: Diagnosticsmentioning

confidence: 99%

The Role of Neutrophils in ANCA-Associated Vasculitis: The Pathogenic Role and Diagnostic Utility of Autoantibodies

Walulik,

Łysak,

Błaszkiewicz

et al. 2023

IJMS

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Recent years have brought progress in understanding the role of the neutrophil, dispelling the dogma of homogeneous cells mainly involved in the prime defence against pathogens, shedding light on their pathogenic role in inflammatory diseases and on the importance of antineutrophil-cytoplasmic antibodies’ pathogenic role in ANCA-associated vasculitides vasculitis (AAV). Myeloperoxidase (MPO) and proteinase 3 (PR3) expressed in neutrophil granulocytes are the most common targets for ANCAs and contribute to the formation of MPO-ANCAs and PR3-ANCAs which, released to the bloodstream, become an excellent diagnostic tool for AAV. In this study, we focus on increasing the clinical and experimental evidence that supports the pathogenic role of ANCAs in AAV. Additionally, we discuss the diagnostic utility of ANCAs for disease activity and prognosis in AAV. Understanding the central role of ANCAs in AAV is crucial for advancing our knowledge of these complex disorders and developing targeted therapeutic strategies in the era of personalized medicine.

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“…Anti-BPI autoantibodies have been peculiar for a number of reasons, most notably their strong linkage with patients suffering from various diseases, particularly cystic fibrosis (CF) [ 10 , 75 , 76 ] and bronchiectasis [ 6 , 67 ], but also including inflammatory bowel diseases (IBD) [ 63 , 77 , 78 ], vasculitis [ 63 , 67 , 68 , 79 ], reactive arthritis [ 80 ], necrotizing and crescentic glomerulonephritis [ 81 ], and primary sclerosing cholangitis [ 82 , 83 ]. The etiopathogenesis of BPI autoantibodies is unknown.…”

Section: Autoantibodies To Bpi and Their Impact On Bpi-dependent Immunitymentioning

confidence: 99%

Killing three birds with one BPI: Bactericidal, opsonic, and anti-inflammatory functions

Theprungsirikul

Skopelja-Gardner

Rigby

2021

Journal of Translational Autoimmunity

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Bactericidal/permeability-increasing protein (BPI) is an anti-microbial protein predominantly expressed in azurophilic granules of neutrophils. BPI has been shown to mediate cytocidal and opsonic activity against Gram-negative bacteria, while also blunting inflammatory activity of lipopolysaccharide (LPS). Despite awareness of these functions in vitro, the magnitude of the contribution of BPI to innate immunity remains unclear, and the nature of the functional role of BPI in vivo has been submitted to limited investigation. Understanding this role takes on particular interest with the recognition that autoimmunity to BPI is tightly linked to a specific infectious trigger like Pseudomonas aeruginosa in chronic lung infection. This has led to the notion that anti-BPI autoantibodies compromise the activity of BPI in innate immunity against P. aeruginosa , which is primarily mediated by neutrophils. In this review, we explore the three main mechanisms in bactericidal, opsonic, and anti-inflammatory of BPI. We address the etiology and the effects of BPI autoreactivity on BPI function. We explore BPI polymorphism and its link to multiple diseases. We summarize BPI therapeutic potential in both animal models and human studies, as well as offer therapeutic approaches to designing a sustainable and promising BPI molecule.

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Systemic Vasculitis Associated with Anti-Neutrophil Cytoplasmic Antibodies against Bactericidal/Permeability Increasing Protein

Cited by 10 publications

References 19 publications

Pathogenesis and therapeutic interventions for ANCA-associated vasculitis

Pathogenesis and therapeutic interventions for ANCA-associated vasculitis

The Role of Neutrophils in ANCA-Associated Vasculitis: The Pathogenic Role and Diagnostic Utility of Autoantibodies

Killing three birds with one BPI: Bactericidal, opsonic, and anti-inflammatory functions

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