Immune stimulatory effects of neutrophil extracellular traps in granulomatosis with polyangiitis.
Clin Exp Rheumatol
; 35 Suppl 103(1): 33-39, 2017.
Article
em En
| MEDLINE
| ID: mdl-28281454
ABSTRACT
OBJECTIVES:
The aim of this study was to analyse the role of netting neutrophils in the pathogenesis of granulomatosis with polyangiitis (GPA), especially their interplay with peripheral blood mononuclear cells (PBMCs).METHODS:
The amount of cell-free DNA (cfDNA) was determined in sera from GPA patients (pairs active/inactive state of disease, n=18) and from healthy controls (HCs, n=10). Furthermore, we performed in vitro incubation experiments using PBMCs and NETs from patients and HCs for accessing the effect of NETs on PBMC behaviour. We determined proliferation of T- and B-cells (CSFE assay), B-cell maturation (CD38 staining and flow cytometry), production of IgG (ELISpot, ELISA), and secretion of the cytokines IFN-γ, IL-4, IL-10, IL-17A (ELISA).RESULTS:
We detected a significant increase in serum cfDNA levels of GPA patients compared to HCs. The concentration of cfDNA was associated with disease activity. NETs of patients and HCs induced proliferation of CD4+ T- cells and CD19+ B-cells and maturation of B-cells. Furthermore, we detected an increase in IL-17A secretion after stimulating PBMCs with NETs. A significant difference between PBMCs from GPA patients and HCs was not detectable.CONCLUSIONS:
NETs activate PBMCs of HCs and GPA patients. Our findings give supportive evidence that NETosis plays a role in the pathogenesis of GPA.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Ativação Linfocitária
/
Linfócitos T
/
Granulomatose com Poliangiite
/
Comunicação Parácrina
/
Armadilhas Extracelulares
/
Neutrófilos
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article