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Immune stimulatory effects of neutrophil extracellular traps in granulomatosis with polyangiitis.
- Source :
-
Clinical and experimental rheumatology [Clin Exp Rheumatol] 2017 Mar-Apr; Vol. 35 Suppl 103 (1), pp. 33-39. Date of Electronic Publication: 2017 Mar 08. - Publication Year :
- 2017
-
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).<br />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).<br />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.<br />Conclusions: NETs activate PBMCs of HCs and GPA patients. Our findings give supportive evidence that NETosis plays a role in the pathogenesis of GPA.
- Subjects :
- B-Lymphocytes metabolism
Biomarkers blood
Case-Control Studies
Cell Proliferation
Cells, Cultured
DNA blood
Extracellular Traps metabolism
Female
Granulomatosis with Polyangiitis blood
Granulomatosis with Polyangiitis diagnosis
Humans
Interleukin-17 blood
Male
Neutrophils metabolism
Phenotype
T-Lymphocytes metabolism
Th17 Cells immunology
Th17 Cells metabolism
B-Lymphocytes immunology
Extracellular Traps immunology
Granulomatosis with Polyangiitis immunology
Lymphocyte Activation
Neutrophils immunology
Paracrine Communication
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0392-856X
- Volume :
- 35 Suppl 103
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical and experimental rheumatology
- Publication Type :
- Academic Journal
- Accession number :
- 28281454