The oxidation induced by antimyeloperoxidase antibodies triggers fibrosis in microscopic polyangiitis

Area of Science:

• Immunology
• Pulmonology
• Pathophysiology

Background:

• Microscopic polyangiitis (MPA) is an autoimmune disease often associated with severe lung fibrosis.
• Antimyeloperoxidase (anti-MPO) antibodies in MPA patients can activate myeloperoxidase (MPO), generating reactive oxygen species (ROS).
• Low levels of ROS can stimulate fibroblast proliferation, a key process in fibrosis.

Purpose of the Study:

• To investigate the hypothesis that oxidative stress induced by anti-MPO antibodies contributes to lung fibrosis in MPA.
• To quantify oxidative stress markers and fibroblast proliferation in MPA patients with and without lung fibrosis.

Main Methods:

• Serum samples from 24 MPA patients (9 with lung fibrosis) and healthy controls were analyzed.
• Assays were performed for advanced oxidation protein products (AOPP), MPO-induced hypochlorous acid (HOCl) production, and serum-induced fibroblast proliferation.
• Statistical analyses were used to compare groups and identify relationships between markers and disease severity.

Main Results:

• MPA patients exhibited significantly higher levels of AOPP, MPO-induced HOCl, and fibroblast proliferation compared to healthy controls.
• Increased HOCl production correlated with active MPA disease.
• Patients with active MPA and lung fibrosis showed elevated serum AOPP and fibroblast proliferation.
• A significant linear relationship between fibroblast proliferation, AOPP, and HOCl was found specifically in patients with lung fibrosis.

Conclusions:

• Oxidative stress, driven by MPO activation via anti-MPO antibodies, plays a crucial role in triggering lung fibrosis in MPA.
• HOCl production is a key mediator in the fibrotic process associated with anti-MPO antibody-mediated MPA.
• Targeting oxidative stress pathways may offer a therapeutic strategy for lung fibrosis in MPA.