Microparticles expressing myeloperoxidase as potential biomarkers in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV)

M Manojlovic; A Juto; A Jonasdottir; J Colic; J Vojinovic; A Nordin; A Bruchfeld; I Gunnarsson; F Mobarrez; A Antovic

doi:10.1007/s00109-020-01955-2

Microparticles expressing myeloperoxidase as potential biomarkers in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV)

J Mol Med (Berl). 2020 Sep;98(9):1279-1286. doi: 10.1007/s00109-020-01955-2. Epub 2020 Jul 30.

Authors

M Manojlovic¹, A Juto², A Jonasdottir³, J Colic⁴, J Vojinovic¹, A Nordin², A Bruchfeld³, I Gunnarsson², F Mobarrez⁵, A Antovic⁶

Affiliations

¹ Department of Pediatrics, Medical Faculty, University of Nis, Nis, Serbia.
² Department of Medicine, Division of Rheumatology Karolinska Institutet and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
³ Renal medicine, CLINTEC, Karolinska University Hospital and Karolinska Institutet, Solna, Stockholm, Sweden.
⁴ Department of Rheumatology, Institute of Rheumatology, Belgrade, Serbia.
⁵ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁶ Department of Medicine, Division of Rheumatology Karolinska Institutet and Rheumatology, Karolinska University Hospital, Stockholm, Sweden. aleksandra.antovic@ki.se.

Abstract

To investigate presence of circulating myeloperoxidase-positive microparticles (MPO⁺MPs) in relation to disease activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MPs were analyzed in citrate plasma by flow cytometry and phenotyped based on MPO expression and co-expression of pentraxin-3 (PTX3), high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. Twenty-three patients had active vasculitis (BVAS ≥ 1). Concentrations of MPO⁺MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls (p < 0.001, p < 0.01, p < 0.001, respectively), while concentrations of PTX3⁺ and HMGB1⁺MPO⁺MPs were significantly higher in active AAV compared to patients in remission. MPO⁺MPs expressing either PTX3 or HMGB1 were associated with BVAS (r = 0.5, p < 0.001; r = 0.3, p = 0.04, respectively). Significantly higher serum PTX3 levels were found in active- than in inactive AAV (p < 0.001), correlating strongly with BVAS (r = 0.7, p < 0.001). Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Concentration of MPO⁺MPs is increased in plasma from AAV patients compared to healthy individuals. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO⁺MPs were associated with disease activity in the investigated patients. KEY MESSAGES: Myeloperoxidase-positive microparticles (MPO⁺MPs) are increased in plasma from patients with ANCA-associated vasculitis. Concentrations of MPO⁺MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls. MPO⁺MPs expressing PTX3 and HMGB1 are associated with disease activity in ANCA-associated vasculitis.

Keywords: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis; Biomarkers; Microparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / diagnosis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / etiology*
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / metabolism*
Antibodies, Antineutrophil Cytoplasmic / immunology
Biomarkers*
Cell-Derived Microparticles / metabolism*
Cross-Sectional Studies
Disease Susceptibility
Female
Flow Cytometry
Humans
Male
Peroxidase / genetics*
Peroxidase / metabolism
Severity of Illness Index

Substances

Antibodies, Antineutrophil Cytoplasmic
Biomarkers
Peroxidase