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Neutrophil-related and serum biomarkers in granulomatosis with polyangiitis support extracellular traps mechanism of the disease
M. Surmiak1, M. Hubalewska-Mazgaj2, K. Wawrzycka-Adamczyk3, W. Szczeklik4, J. Musiał5, T. Brzozowski6, M. Sanak7
- Department of Internal Medicine, and Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
- Department of Internal Medicine, and Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
- Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
- Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
- Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
- Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
- Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. nfsanak@cyf-kr.edu.pl
CER9186
2016 Vol.34, N°3 ,Suppl.97
PI 0098, PF 0104
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PMID: 27192020 [PubMed]
Received: 13/12/2015
Accepted : 29/02/2016
In Press: 17/05/2016
Published: 27/05/2016
Abstract
OBJECTIVES:
Granulomatosis with polyangiitis (GPA) is an autoimmune disease with still unknown etiology. Recent studies indicate that neutrophils extra-cellular traps participate in the pathophysiology of GPA. This study investigates the levels of circulating NET formation markers and neutrophil-platelet interaction in patients with GPA.
METHODS:
We enrolled 40 GPA patients (20 in the active stage of the disease and 20 in remission). Twenty sex- and age-matched healthy subjects served as a control group. Serum/plasma levels of serine proteases, and histone-, myeloperoxidase-, proteinase-3 DNA complexes and sP-selectin were measured using ELISA or Luminex assays. Circulating platelet-neutrophil aggregates and neutrophils activation markers expression was measured by flow cytometry.
RESULTS:
Patients in active stage of GPA had higher circulating levels of serine proteases, DNA-histone and myeloperoxidase -DNA complexes. In addition, platelet-neutrophil aggregates and sP-selectin were also elevated in this group. Platelet-neutrophil aggregates and myeloperoxidase -DNA complexes correlated positively with the disease activity score (BVAS).
CONCLUSIONS:
NETs production and activation of platelets in GPA is supported by elevated myeloperoxidase-DNA complexes and platelet-neutrophil aggregates correlating positively with the disease activity score. This mechanism justifies laboratory measurements of myeloperoxidase-DNA complexes and plasma sP-selectin as biomarkers for studying GPA activity.