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

Autor: Christina Hansson, Lisa Holm, Susanne M. Ohlsson, Åsa Pettersson, Lena Gunnarsson, Lillemor Skattum, Sophie Ohlsson
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Neutrophils
Physiology
Complement System
Microscopic Polyangiitis
Pathogenesis
Pathology and Laboratory Medicine
Biochemistry
White Blood Cells
0302 clinical medicine
Animal Cells
Immune Physiology
Medicine and Health Sciences
Complement Activation
Multidisciplinary
Immune System Proteins
biology
medicine.diagnostic_test
Chemistry
Animal Models
Experimental Organism Systems
Medicine
Female
Antibody
medicine.symptom
Cellular Types
Microscopic polyangiitis
Granulomatosis with polyangiitis
Research Article
Vasculitis
Science
Immune Cells
Inflammatory Diseases
Immunology
Inflammation
Mouse Models
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Complement C5a
Enzyme-Linked Immunosorbent Assay
Research and Analysis Methods
Flow cytometry
Autoimmune Diseases
Antibodies
Antineutrophil Cytoplasmic
03 medical and health sciences
Model Organisms
Rheumatology
medicine
Animals
Humans
Wegener Granulomatosis
Aged
030203 arthritis & rheumatology
Blood Cells
Properdin
Granulomatosis with Polyangiitis
Biology and Life Sciences
Proteins
Cell Biology
medicine.disease
Complement system
030104 developmental biology
Immune System
Immunoglobulin G
biology.protein
Alternative complement pathway
Animal Studies
Clinical Immunology
Clinical Medicine
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 6, p e0218272 (2019)
ISSN: 1932-6203
Popis: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), are autoimmune conditions associated with small vessel inflammation. Earlier studies indicate that complement activation via the alternative pathway plays a major role in the pathogenesis. In this study we have investigated if ANCA-activation of neutrophils from AAV patients leads to activation of the alternative complement pathway. C5a-primed neutrophils (PMN) from 10 AAV patients and 10 healthy controls (HC) were stimulated with PMA or IgG purified from PR3-ANCA positive patients (ANCA IgG). The supernatants were analyzed for release of complement proteins and markers of different granules by ELISA, and release of microparticles (MP) by flow cytometry. The ability of the supernatants to activate the alternative complement pathway was determined by incubation with normal serum and C3bBbP and C5a were measured by ELISA. MP were analyzed by flow cytometry and removed by centrifugation. The supernatants from the AAV patients' neutrophils produced significantly more C3bBbP compared with HCs (p = 0.0001). C3bBbP levels correlated with the number of MP. After removal of MP from the supernatants, alternative pathway activation was significantly lower. This study shows that primed and ANCA-stimulated neutrophils from AAV patients have a greater ability to activate the alternative complement pathway compared to primed neutrophils from healthy controls. This finding emphasizes the role of complement in the pathogenesis of AAV - underlining the therapeutic potential of C5a and other complement blockade.
Databáze: OpenAIRE
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