Marcin Surmiak1, Magdalena Hubalewska-Mazgaj1, Katarzyna Wawrzycka-Adamczyk2, Wojciech Szczeklik2, Jacek Musiał2, Tomasz Brzozowski3, Marek Sanak4. 1. Department of Internal Medicine, and Department of Physiology, Jagiellonian University Medical College, Krakow, Poland. 2. Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. 3. Department of Physiology, Jagiellonian University Medical College, Krakow, Poland. 4. Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. nfsanak@cyf-kr.edu.pl.
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.
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.
Authors: Marcin Surmiak; Katarzyna Wawrzycka-Adamczyk; Joanna Kosałka-Węgiel; Stanisław Polański; Marek Sanak Journal: Clin Exp Immunol Date: 2022-05-13 Impact factor: 4.330
Authors: Marcin Surmiak; Katarzyna Wawrzycka-Adamczyk; Joanna Kosałka-Węgiel; Stanisław Polański; Marek Sanak Journal: Clin Exp Immunol Date: 2022-03-03 Impact factor: 5.732
Authors: Miriana d'Alessandro; Edoardo Conticini; Laura Bergantini; Paolo Cameli; Luca Cantarini; Bruno Frediani; Elena Bargagli Journal: Life (Basel) Date: 2022-02-20