A Myeloperoxidase Antibody (MPO Ab) is an autoantibody, a protein produced by the immune system that mistakenly targets the body’s own components. The MPO Ab specifically recognizes and binds to the myeloperoxidase enzyme, which is normally found inside certain white blood cells. The presence of this autoantibody serves as an important diagnostic marker for serious autoimmune diseases that primarily cause inflammation of blood vessels. Determining the level of MPO antibodies is a standard step in evaluating patients with systemic inflammation.
What Is Myeloperoxidase and Its Role
Myeloperoxidase (MPO) is a heme-containing enzyme highly concentrated within neutrophils and monocytes, the immune system’s first responders. This enzyme is stored inside small compartments within these cells called azurophilic granules.
The primary function of MPO is to act as a powerful component of the innate immune defense system against invading pathogens, such as bacteria and fungi. When a neutrophil encounters a threat, it undergoes a respiratory burst, producing hydrogen peroxide. MPO utilizes this hydrogen peroxide along with chloride ions to catalyze the production of hypochlorous acid (HOCl).
Hypochlorous acid is a potent oxidizing agent, making it effective at destroying microorganisms. This microbicidal activity is normally contained within the neutrophil to prevent damage to the body’s own tissues. However, when MPO is released outside the cell during an uncontrolled inflammatory process, it can cause damage to surrounding host cells and tissues.
The Autoantibody Target: MPO-ANCA
The Myeloperoxidase Antibody is a specific type of Anti-Neutrophil Cytoplasmic Antibody (ANCA), often referred to clinically as MPO-ANCA. ANCA are autoantibodies that target components within the cytoplasm of neutrophils. When tested using indirect immunofluorescence (IFA), MPO-ANCA is responsible for a characteristic laboratory staining pattern known as perinuclear ANCA, or p-ANCA.
When MPO-ANCA binds to the MPO enzyme expressed on the surface of an activated neutrophil, it triggers a cascade of events. This binding causes the neutrophil to become hyper-activated, leading to degranulation, where the cell prematurely releases its toxic contents.
This premature release includes MPO and other destructive enzymes into the surrounding microenvironment, particularly near blood vessel walls. The resulting inflammatory response damages the endothelium, the inner lining of the blood vessels, leading to vasculitis. This autoimmune attack drives the clinical symptoms seen in MPO-associated diseases.
The Link to Autoimmune Vasculitis
MPO-ANCA is strongly associated with ANCA-Associated Vasculitis (AAV), a group of autoimmune disorders causing inflammation and necrosis of small-to-medium-sized blood vessels. This vasculitis is described as “pauci-immune,” meaning immune complex deposits are largely absent. The MPO-ANCA subtype is the primary serological marker for Microscopic Polyangiitis (MPA).
MPA is a systemic disorder that affects multiple organ systems, with the most severe damage occurring in the kidneys and lungs. Approximately 80% of MPA patients experience kidney inflammation, manifesting as rapidly progressive glomerulonephritis. This involves inflammation within the kidney’s filtering units, which can quickly cause irreversible injury and lead to kidney failure.
Damage to the lungs results in pulmonary capillaritis, inflammation of the tiny capillaries, potentially leading to pulmonary hemorrhage. Other frequently involved organs include the skin, causing palpable purpura, and the peripheral nervous system, causing mononeuritis multiplex. The presence of MPO-ANCA in a patient with a rapidly progressing systemic illness suggests this diagnosis.
Testing Methods and Interpreting Results
The detection of MPO antibodies typically involves two main laboratory techniques: Indirect Immunofluorescence (IFA) and Enzyme-Linked Immunosorbent Assay (ELISA). IFA is the traditional method, using patient serum to stain ethanol-fixed neutrophils, which yields the perinuclear (p-ANCA) pattern. However, the IFA method can sometimes produce false-positive results because other autoantibodies can also cause this pattern.
The ELISA test is an antigen-specific immunoassay that directly measures the level, or titer, of antibodies against purified MPO protein. Modern clinical guidelines recommend that high-quality, antigen-specific immunoassays, such as ELISA, be used as the primary screening method for suspected AAV. This provides a quantitative result, usually expressed in international units per milliliter (IU/mL) or relative units (RU/mL).
Interpreting the results involves monitoring the antibody titer, which is important for tracking disease activity. High MPO-ANCA titers correlate with active, severe disease, particularly when the kidneys are involved. Successfully treated patients often show a significant drop in MPO-ANCA levels, and persistent negativity indicates remission and a low risk for relapse.
Managing MPO-Associated Disease
The management of MPO-associated vasculitis follows a two-phased approach involving intensive immunosuppression to achieve disease control. The first phase, induction therapy, aims to quickly halt active inflammation and prevent further organ damage. This typically involves high-dose glucocorticoids, such as prednisone, combined with a potent immunosuppressive agent like cyclophosphamide or the B-cell depleting antibody rituximab.
Once the disease is in remission, the second phase, maintenance therapy, begins, focusing on preventing disease flares and reducing long-term treatment side effects. This phase uses lower doses of immunosuppressants, such as azathioprine, mycophenolate mofetil, or continued, less frequent rituximab infusions. Rituximab has proven highly effective for maintenance, often showing superior results in preventing relapse compared to conventional drugs.
Patients who are MPO-ANCA positive are considered to have a lower risk of relapse compared to those with antibodies against proteinase 3 (PR3-ANCA). The duration of maintenance treatment is tailored to the individual, but the goal is to safely minimize immunosuppression, especially in patients who maintain MPO-ANCA negative status. Ongoing specialized care and regular monitoring of MPO antibody levels are necessary to detect early signs of relapse.