From the Guidelines
High myeloperoxidase (MPO) levels are primarily caused by inflammatory conditions, infections, and certain autoimmune disorders, as well as oxidative stress in chronic kidney disease (CKD) patients, as evidenced by increased generation of oxidants in CKD 1.
Causes of High MPO
- Inflammatory conditions, such as rheumatoid arthritis and vasculitis
- Infections, including bacterial infections
- Certain autoimmune disorders
- Cardiovascular diseases
- Myeloid leukemias and bone marrow disorders
- Smoking, due to chronic inflammation
- Oxidative stress in CKD patients, which can be caused by factors such as advanced age, diabetes, uremia, chronic inflammation, and malnutrition 1
Mechanism of High MPO
MPO is an enzyme found mainly in neutrophils, a type of white blood cell that fights infections. When the body is fighting an infection or experiencing inflammation, neutrophils release MPO as part of the immune response. In CKD patients, the balance between pro- and anti-oxidant capacities is shifted towards an increased oxidative stress, which can lead to elevated MPO levels 1.
Clinical Significance of High MPO
High MPO levels can serve as a marker of inflammation and oxidative stress, and can be associated with an increased risk of cardiovascular events and mortality in CKD patients 1. Therefore, it is essential to investigate the underlying cause of high MPO levels and recommend treatments targeting the specific condition rather than the MPO level itself.
From the Research
Causes of High MPO
- High levels of myeloperoxidase (MPO) have been observed in several inflammatory diseases, including rheumatoid arthritis (RA) 2, 3, 4.
- The clinical significance of MPO has been the focus of investigation because it may contribute to the chronic, non-microbial inflammatory process in various diseases 2.
- Elevated MPO levels are associated with inflammation and increased oxidative stress, which can lead to cardiovascular disease (CVD) 5.
- MPO-derived reactive species play a key role in neutrophil antimicrobial activity and human defense against various pathogens, but can also promote inflammation and cause tissue damage in the setting of sterile inflammation 4.
- MPO levels have been shown to be higher in patients with active rheumatoid arthritis, and are associated with disease activity indicators such as C-reactive protein and neutrophil percentage 2.
Associated Conditions
- Rheumatoid arthritis (RA) 2, 3, 4
- Systemic lupus erythematosus (SLE) 2
- Primary Sjögren's syndrome (pSS) 2
- Dermatomyositis (DM) 2
- Ankylosing spondylitis (AS) 2
- Cardiovascular disease (CVD) 5
- Multiple sclerosis (MS) 4
Mechanisms
- MPO utilizes H2O2 to generate hypochlorous acid (HClO) and other reactive moieties, which can kill pathogens during infections, but also promote inflammation and cause tissue damage in the setting of sterile inflammation 4.
- MPO can limit the extent of immune responses, but also contribute to disease pathogenesis by tuning of adaptive immune responses and/or the induction of vascular permeability 4.
- MPO produces a large number of highly reactive species which can attack, destroy or modify the function of every known cellular component, leading to endothelial dysfunction, impaired vasoreactivity, and atherosclerotic plaque instability 5.