Aleksandra Antovic1,2, Fariborz Mobarrez3,4, Milena Manojlovic3,4, Nida Soutari3,4, Victoria De Porta Baggemar3,4, Annica Nordin3,4, Annette Bruchfeld3,4, Jelena Vojinovic3,4, Iva Gunnarsson3,4. 1. From the Division of Rheumatology, Department of Medicine, Department of Molecular Medicine and Surgery, Clinical Chemistry, and Renal Medicine, Karolinska Institutet; Rheumatology, Karolinska University Hospital; CLINTEC Karolinska University Hospital, Renal Medicine, Karolinska Institutet, Stockholm; Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Pediatrics, Medical Faculty, University of Niš, Niš, Serbia. aleksandra.antovic@ki.se. 2. A. Antovic, MD, PhD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital; F. Mobarrez, PhD, Department of Medical Sciences, Uppsala University; M. Manojlovic, MD, Department of Pediatrics, Medical Faculty, University of Niš; N. Soutari, BMS, MS, Department of Molecular Medicine and Surgery, Clinical Chemistry, Karolinska Institutet; V. De Porta Baggemar, MD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital; A. Nordin, MD, PhD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital; A. Bruchfeld, MD, PhD, Renal Medicine, CLINTEC Karolinska University Hospital and Karolinska Institutet; J. Vojinovic, MD, PhD, Department of Pediatrics, Medical Faculty, University of Niš; I. Gunnarsson, MD, PhD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital. aleksandra.antovic@ki.se. 3. From the Division of Rheumatology, Department of Medicine, Department of Molecular Medicine and Surgery, Clinical Chemistry, and Renal Medicine, Karolinska Institutet; Rheumatology, Karolinska University Hospital; CLINTEC Karolinska University Hospital, Renal Medicine, Karolinska Institutet, Stockholm; Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Pediatrics, Medical Faculty, University of Niš, Niš, Serbia. 4. A. Antovic, MD, PhD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital; F. Mobarrez, PhD, Department of Medical Sciences, Uppsala University; M. Manojlovic, MD, Department of Pediatrics, Medical Faculty, University of Niš; N. Soutari, BMS, MS, Department of Molecular Medicine and Surgery, Clinical Chemistry, Karolinska Institutet; V. De Porta Baggemar, MD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital; A. Nordin, MD, PhD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital; A. Bruchfeld, MD, PhD, Renal Medicine, CLINTEC Karolinska University Hospital and Karolinska Institutet; J. Vojinovic, MD, PhD, Department of Pediatrics, Medical Faculty, University of Niš; I. Gunnarsson, MD, PhD, Division of Rheumatology, Department of Medicine, Karolinska Institutet, and Rheumatology, Karolinska University Hospital.
Abstract
OBJECTIVE: To investigate expression of terminal complement components C3a and C5a on circulating myeloperoxidase (MPO)-positive microparticles (MPO+MP) in relation to disease activity and renal involvement in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Forty-six clinically well-characterized patients with AAV and 23 age- and sex-matched healthy controls were included. The concentration of MPO+MP expressing C3a and C5a was analyzed from citrate plasma by flow cytometry. Serum levels of C3a and C5a were determined using commercial ELISA. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS). Among patients, 23 had active disease with BVAS ≥ 2 and 14 patients had active renal flares. RESULTS: AAV patients had significantly increased expression of C3a and C5a on MPO+MP compared to controls (both p < 0.0001). When the group of patients with active AAV was divided according to the presence of renal activity, the concentration of MPO+MP expressing C3a and C5a was significantly higher in patients with renal involvement compared to patients with nonrenal disease and controls (p < 0.05 and p < 0.01, respectively). The serum levels of C3a were significantly decreased (p < 0.01) in the renal subgroup, while there were no changes in serum levels of C5a comparing the renal and nonrenal groups. There was significant correlation between the disease activity measured by BVAS and the levels of C3a and C5a expressed on MPO+MP. CONCLUSION: Determination of C3a and C5a on MPO+MP might be considered as a novel biomarker of renal involvement in patients with AAV and may be of importance in the pathogenetic process.
OBJECTIVE: To investigate expression of terminal complement components C3a and C5a on circulating myeloperoxidase (MPO)-positive microparticles (MPO+MP) in relation to disease activity and renal involvement in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Forty-six clinically well-characterized patients with AAV and 23 age- and sex-matched healthy controls were included. The concentration of MPO+MP expressing C3a and C5a was analyzed from citrate plasma by flow cytometry. Serum levels of C3a and C5a were determined using commercial ELISA. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS). Among patients, 23 had active disease with BVAS ≥ 2 and 14 patients had active renal flares. RESULTS: AAV patients had significantly increased expression of C3a and C5a on MPO+MP compared to controls (both p < 0.0001). When the group of patients with active AAV was divided according to the presence of renal activity, the concentration of MPO+MP expressing C3a and C5a was significantly higher in patients with renal involvement compared to patients with nonrenal disease and controls (p < 0.05 and p < 0.01, respectively). The serum levels of C3a were significantly decreased (p < 0.01) in the renal subgroup, while there were no changes in serum levels of C5a comparing the renal and nonrenal groups. There was significant correlation between the disease activity measured by BVAS and the levels of C3a and C5a expressed on MPO+MP. CONCLUSION: Determination of C3a and C5a on MPO+MP might be considered as a novel biomarker of renal involvement in patients with AAV and may be of importance in the pathogenetic process.
Authors: S Moiseev; J M Lee; A Zykova; N Bulanov; P Novikov; E Gitel; M Bulanova; E Safonova; J I Shin; A Kronbichler; D R W Jayne Journal: Clin Exp Immunol Date: 2020-09-15 Impact factor: 4.330