Related Experiment Video
Updated: Jul 14, 2026
Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4
Published on: August 21, 2017
Pathogenic effects of antimyeloperoxidase antibodies in patients with microscopic polyangiitis
Philippe Guilpain1, Amélie Servettaz, Claire Goulvestre
1Université Paris Descartes, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France.
Objective:
Microscopic polyangiitis (MPA) is a small-vessel vasculitis associated with antimyeloperoxidase (MPO) antibodies in 70% of patients. Anti-MPO antibodies can trigger the release of MPO by neutrophils and monocytes, but their involvement in the pathogenesis of MPA is still questioned. The aim of this study was to investigate whether anti-MPO antibodies can activate MPO to generate an oxidative stress that is potentially deleterious to the endothelium.
Methods:
MPA sera, purified IgG from MPA sera, normal control sera, and purified IgG from normal sera were incubated with MPO coated onto microtitration plates. The peroxidase activity of MPO was evaluated by adding o-phenylenediamine. Production of hypochlorous acid (HOCl) was determined by chemiluminescence. The cytotoxic properties of byproducts of MPO activation were tested on endothelial cells in culture.
Results:
MPA sera with anti-MPO antibodies were found to activate MPO in vitro (P < 0.0001 versus normal sera) and to generate HOCl (P < 0.001), as did IgG purified from MPA sera (P < 0.05). MPA sera without anti-MPO antibodies and MPA IgG absorbed on MPO did not show these activities. The byproducts of MPO activation by MPA sera exerted a strong cytolytic activity on endothelial cells in culture (P < 0.01). Both HOCl production and endothelial lysis were abrogated by N-acetylcysteine (NAC), an antioxidant molecule (P < 0.05 and P < 0.0001, respectively).
Conclusion:
Anti-MPO antibodies could play a pathogenic role in vivo by triggering an oxidative burst, leading to severe endothelial damage. Treatment of MPA patients with NAC might be proposed in an attempt to abrogate these deleterious phenomena.
Insights
Antimyeloperoxidase (MPO) antibodies in microscopic polyangiitis (MPA) activate MPO, causing oxidative stress and endothelial damage. N-acetylcysteine (NAC) may mitigate these harmful effects in MPA patients.
Area of Science:
- Immunology
- Pathophysiology
- Oxidative Stress
Background:
- Microscopic polyangiitis (MPA) is a small-vessel vasculitis often associated with antimyeloperoxidase (MPO) antibodies.
- The precise role of anti-MPO antibodies in MPA pathogenesis, particularly in triggering endothelial damage, remains under investigation.
Purpose of the Study:
- To determine if anti-MPO antibodies can activate MPO to generate oxidative stress.
- To assess the potential for MPO activation byproducts to cause endothelial cell damage.
Main Methods:
- Incubation of MPO with sera and purified IgG from MPA patients and healthy controls.
- Assay of MPO peroxidase activity and hypochlorous acid (HOCl) production.
- Testing the cytotoxicity of MPO activation byproducts on cultured endothelial cells.
- Evaluation of N-acetylcysteine (NAC) as a potential inhibitor.
Main Results:
- MPA sera with anti-MPO antibodies significantly activated MPO and produced HOCl in vitro.
- Purified IgG from MPA patients also demonstrated MPO activation and HOCl generation.
- MPO activation byproducts exhibited significant cytolytic activity on endothelial cells.
- NAC effectively abrogated both HOCl production and endothelial cell lysis.
Conclusions:
- Anti-MPO antibodies may contribute to MPA pathogenesis by initiating an oxidative burst that damages the endothelium.
- N-acetylcysteine (NAC) shows potential as a therapeutic agent to counteract MPO-induced endothelial damage in MPA.
Related Concept Videos
01:22Myasthenia Gravis ll: Pathophysiology
01:30Peripheral Artery Disease I: Introduction
01:14Atypical Pneumonia
01:20Myasthenia Gravis: Overview and Treatment
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which leads...