Myeloperoxidase (MPO) is a heme-containing enzyme found primarily within neutrophils, a type of white blood cell. These immune cells release MPO during an inflammatory response, where the enzyme acts as a powerful part of the body’s defense system. The myeloperoxidase assay is a laboratory test designed to measure the concentration or activity of this enzyme in biological samples. Quantifying MPO levels provides insight into the degree of inflammation and oxidative stress occurring within the body.
Myeloperoxidase: The Immune System’s Double-Edged Sword
Myeloperoxidase is housed in the azurophilic granules of neutrophils, which are the most abundant type of white blood cell and one of the first responders to infection. When a neutrophil encounters an invading pathogen, it initiates an “oxidative burst,” a rapid process of oxygen consumption that generates reactive oxygen species. MPO is the central enzyme in this process, utilizing hydrogen peroxide (\(\text{H}_2\text{O}_2\)) and chloride ions (\(\text{Cl}^-\)) to create a potent oxidant called hypochlorous acid (\(\text{HOCl}\)).
Hypochlorous acid, the active chemical found in household bleach, is effective at destroying bacteria, fungi, and other microorganisms. MPO’s ability to generate this microbicidal agent is central to the innate immune system’s ability to clear infections.
MPO is considered a “double-edged sword” because its potent microbicidal action can also cause collateral damage to the host’s own tissues. While MPO is essential for defense, the uncontrolled or excessive release of hypochlorous acid and other MPO-derived oxidants can damage lipids, proteins, and DNA in surrounding healthy cells. This oxidative tissue damage contributes significantly to the progression of chronic inflammatory conditions.
The enzyme’s cationic nature allows it to bind to negatively charged components of the extracellular matrix and cell surfaces. This concentrates the destructive oxidative process locally, transforming MPO into a contributing factor in the development of diseases characterized by persistent inflammation.
Principles of the Myeloperoxidase Assay
The MPO assay quantifies the enzyme by measuring either its concentration or its functional activity. Measuring the concentration of the MPO protein often involves an immunoassay technique, such as an Enzyme-Linked Immunosorbent Assay (ELISA). This method uses specific antibodies to capture and quantify the total amount of MPO protein present in the plasma or serum sample.
Measuring MPO activity is considered more informative, as it reflects the enzyme’s actual functional capacity rather than just the protein quantity. These functional assays typically rely on MPO’s ability to catalyze a reaction that produces a detectable change, often a shift in color. The intensity of the resulting color is directly proportional to the amount of active MPO in the sample.
One common method for measuring MPO activity involves using a hydrogen donor substrate, such as o-dianisidine (OPD). In the presence of hydrogen peroxide, MPO oxidizes the OPD, which results in a measurable color change, often turning the solution yellow. The rate of color development is monitored using a spectrophotometer, providing a precise reading of the enzyme’s activity level.
Another type of activity assay focuses on MPO’s unique chlorinating function, the production of \(\text{HOCl}\). This method uses a stable chromogen probe that reacts with the \(\text{HOCl}\) product, resulting in a measurable change in light absorbance.
Samples for MPO testing are typically derived from blood, such as serum or plasma. They can also include tissue homogenates or cell lysates when analyzing localized inflammation.
Clinical Applications of MPO Measurement
MPO measurement is primarily valuable as an independent biomarker for inflammatory processes, particularly in assessing cardiovascular risk. Elevated levels of MPO in the bloodstream are strongly associated with the instability of atherosclerotic plaque and damage to the endothelium, the inner lining of blood vessels. This link exists even in patients who have normal cholesterol levels and lack many traditional heart disease risk factors.
MPO contributes to atherosclerosis by promoting the oxidation of low-density lipoprotein (LDL) cholesterol. The highly reactive oxidants generated by MPO modify the LDL particle, creating oxidized LDL (oxLDL), which is readily taken up by macrophages to form foam cells that accumulate in the arterial walls. This process accelerates the buildup of plaque and increases the risk of acute events like heart attack and stroke.
Beyond cardiovascular health, the MPO assay is also used in the diagnosis and management of certain autoimmune diseases. Myeloperoxidase serves as a target autoantigen in a condition called MPO-Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis. This is an autoimmune disease characterized by inflammation and damage to small blood vessels, most commonly affecting the kidneys and lungs.
In these patients, the immune system mistakenly produces antibodies (MPO-ANCA) that target the MPO enzyme, leading to a pathological immune response. Measuring the levels of these autoantibodies is a standard diagnostic procedure for this type of vasculitis.
MPO levels can also monitor the effectiveness of anti-inflammatory therapies and gauge patient prognosis. Persistently high MPO activity or concentration generally signifies a sustained inflammatory burden and increased oxidative stress. Serial measurements can help physicians determine if treatment is successfully lowering systemic inflammation or if a patient remains at high risk for a future adverse cardiac event.
Interpreting the results of an MPO assay requires careful consideration by a healthcare provider, as a high result is not a diagnosis in itself but rather a strong indicator of inflammatory activity. The information is integrated with other clinical data and traditional risk markers to provide a more comprehensive assessment of a patient’s overall inflammatory status and disease risk.