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Updated: Jul 4, 2026
Quantifying Myeloperoxidase-DNA and Neutrophil Elastase-DNA Complexes from Neutrophil Extracellular Traps by Using a Modified Sandwich ELISA
Published on: May 12, 2023
Natural and disease associated anti-myeloperoxidase (MPO) autoantibodies
Philippe Guilpain1, Amélie Servettaz, Frédéric Batteux
1Paris Descartes University, Faculty of Medicine, UPRES EA 4058, Department of Internal Medicine, Paris, France.
Abstract:
Myeloperoxidase (MPO) is a cationic protein present in primary azurophilic granules of neutrophils and monocytes. MPO produces a highly deleterious reactive oxygen species, the hypochlorous acid (HOCl), using hydrogen peroxide (H(2)O(2)) and chloride ions as substrate. Anti-MPO antibodies (Abs) are present in 70% of the cases in patients with microscopic polyangiitis (MPA), a small-sized vessel vasculitis. Anti-MPO Abs from patients with MPA can trigger the release of MPO by neutrophils and monocytes. Anti-MPO Abs can activate MPO to generate an oxidative stress deleterious for the endothelium. Thus, we recently demonstrated that MPA sera with anti-MPO Abs activated MPO in vitro, and generated hypochlorous acid, whereas sera from MPA patients with no anti-MPO Abs or healthy individuals did not. Both hypochlorous acid production and endothelial lysis were abrogated by N-acetylcysteine (NAC), an antioxidant molecule. Thus, anti-MPO Abs could play a pathogenic role in vivo by triggering an oxidative burst leading to severe endothelial damages.
Insights
Anti-myeloperoxidase (MPO) antibodies in microscopic polyangiitis (MPA) activate MPO, generating harmful hypochlorous acid. This oxidative stress damages endothelium, suggesting a pathogenic role for these antibodies in MPA.
Area of Science:
- Biochemistry
- Immunology
- Pathology
Background:
- Myeloperoxidase (MPO) is a neutrophil/monocyte enzyme producing hypochlorous acid (HOCl).
- Anti-MPO antibodies (Abs) are prevalent in microscopic polyangiitis (MPA).
Purpose of the Study:
- To investigate the pathogenic role of anti-MPO Abs in MPA.
- To determine if anti-MPO Abs trigger MPO activation and oxidative stress.
Main Methods:
- Analysis of MPA patient sera for anti-MPO Abs.
- In vitro assessment of MPO activation and HOCl production.
- Evaluation of endothelial cell damage.
- Assessment of N-acetylcysteine (NAC) effects.
Main Results:
- MPA sera with anti-MPO Abs activated MPO and produced HOCl in vitro.
- Sera without anti-MPO Abs or from healthy individuals did not induce MPO activation.
- Endothelial lysis was observed and abrogated by NAC.
Conclusions:
- Anti-MPO Abs may drive MPA pathogenesis by inducing MPO-mediated oxidative damage.
- Targeting MPO-derived oxidative stress with agents like NAC could be therapeutic.
