Anti-MPO antibodies are proteins produced by the immune system that mistakenly target the body’s own components. These autoantibodies are directed against myeloperoxidase (MPO), an enzyme found primarily within certain white blood cells. The presence of Anti-MPO antibodies serves as an important biomarker for detecting specific autoimmune diseases, indicating a breakdown in the immune system’s ability to distinguish between self and non-self proteins.
Understanding Myeloperoxidase and Autoantibodies
Myeloperoxidase (MPO) is an enzyme found in high concentrations within the granules of neutrophils, the most abundant type of white blood cell. MPO’s primary function is to participate in the body’s defense against invading pathogens, such as bacteria and fungi. It uses hydrogen peroxide and chloride ions to generate potent microbicidal agents like hypochlorous acid. This strong oxidant helps destroy trapped microbes inside the neutrophil, enabling effective neutralization of threats as part of the innate immune response.
An autoantibody is an immune protein that incorrectly attacks the individual’s own healthy tissues or cells, leading to autoimmune disease. Anti-MPO antibodies specifically target the myeloperoxidase enzyme, which is normally contained within the neutrophil’s internal structures. The presence of these autoantibodies means the immune system recognizes MPO as a foreign threat. This misdirected attack forms the basis of the pathology seen in several inflammatory conditions.
The Anti-MPO antibody is classified as a type of antineutrophil cytoplasmic antibody (ANCA) because its target is a protein found within the cytoplasm of neutrophils. The interaction between the autoantibody and its target initiates the inflammatory cascade that leads to tissue damage. This molecular interaction explains why these antibodies are closely tied to systemic inflammation.
Anti-MPO Antibodies and Vasculitis
The presence of Anti-MPO antibodies is strongly associated with ANCA-associated vasculitis (AAV). Vasculitis is inflammation of the blood vessel walls, and AAV specifically involves small blood vessels, such as capillaries, venules, and arterioles. Anti-MPO antibodies are the primary serological marker for Microscopic Polyangiitis (MPA), found in approximately 70% of patients with this form of AAV.
The pathogenicity arises when autoantibodies bind to MPO expressed on the surface of neutrophils, often triggered by infection or inflammatory signals. This binding activates the neutrophil, causing it to undergo degranulation and release its toxic contents into the surrounding tissue. These toxic substances include MPO, reactive oxygen species, and destructive enzymes.
This uncontrolled release of destructive molecules causes inflammation and necrosis (cell death) of the small blood vessel walls. The resulting damage restricts blood flow and can lead to organ failure. The kidneys and lungs are the organs most frequently and severely affected by MPO-associated vasculitis.
In the kidneys, this damage manifests as rapidly progressive glomerulonephritis, which is inflammation of the filtering units. Damage to the capillaries in the lungs, known as pulmonary capillaritis, can lead to bleeding into the air sacs and cause severe respiratory symptoms. MPO-associated vasculitis is a serious condition requiring prompt medical attention due to the potential for both kidney and lung involvement.
The Diagnostic Testing Process
Testing for Anti-MPO antibodies is performed when a patient presents with symptoms suggestive of ANCA-associated vasculitis, such as unexplained kidney failure, lung hemorrhage, or systemic inflammation. The testing strategy involves a two-step approach to ensure sensitivity and specificity. The initial screening test is the Indirect Immunofluorescence (IFA) assay, which uses patient serum mixed with ethanol-fixed white blood cells on a slide.
If ANCAs are present, they attach to cellular components and create a fluorescent pattern visible under a microscope. Anti-MPO antibodies produce a perinuclear ANCA pattern, or p-ANCA, because ethanol fixation causes the MPO protein to move toward the cell nucleus. However, the p-ANCA pattern is not exclusive to MPO-ANCA, as other autoantibodies can create a similar staining appearance.
Due to the limited specificity of IFA alone, the Enzyme-Linked Immunosorbent Assay (ELISA) is used as a second test to confirm the specific antigen target. ELISA uses purified MPO protein fixed to a plate to directly capture Anti-MPO antibodies from the patient’s blood sample. This method provides a quantitative result, often reported as a titer or index value, which is specific for MPO-ANCA.
The combination of a positive p-ANCA pattern on IFA and a positive Anti-MPO result on ELISA is highly indicative of MPO-associated AAV, particularly Microscopic Polyangiitis. The quantitative antibody titer is sometimes monitored over time as an indicator of disease activity. The final diagnosis requires correlating the laboratory results with the patient’s clinical symptoms and other medical findings.
Management and Treatment Approaches
Treatment for MPO-associated vasculitis is a two-phased process aimed at halting the autoimmune attack and preventing long-term organ damage. The first phase, Induction therapy, focuses on achieving rapid remission of the active disease, especially with severe organ involvement. This phase involves intensive immunosuppression to quickly suppress the overactive immune response.
High-dose glucocorticoids (steroids) are administered to rapidly reduce inflammation throughout the body. These are often combined with a powerful immunosuppressive agent, such as cyclophosphamide, a cytotoxic drug that reduces the production of immune cells. Alternatively, the biologic drug rituximab, which targets and depletes B-cells (the cells responsible for producing autoantibodies), is also widely used for induction.
Once remission is achieved, patients transition to the second phase, Maintenance therapy, designed to prevent a relapse of the condition. Maintenance treatment is less intense than induction but is often required for a prolonged period, sometimes for several years. Common maintenance drugs include lower doses of glucocorticoids combined with agents like azathioprine or methotrexate.
Rituximab infusions, administered at regular intervals, have also proven effective for maintaining remission, particularly in patients with MPO-associated vasculitis. Treatment plans are highly individualized based on the patient’s specific organ involvement, overall health status, and the risk of side effects from the powerful medications. The goal is to balance the need for immune suppression with minimizing the risk of infection and long-term medication toxicity.