Myeloperoxidase

Myeloperoxidase (MPO) is a leukocyte-derived enzyme that catalyzes the formation of variety of reactive oxygen species that contribute to inflammatory tissue damage.

From: Advances in Clinical Chemistry, 2023

Chapters and Articles

Granulocytic Disorders

Faramarz Naeim MD, ... Ryan T. Phan PhD, in Atlas of Hematopathology (Second Edition), 2018

63.2.1 Myeloperoxidase Deficiency

MPO deficiency is the most common intrinsic granulocytic functional deficiency. It is an autosomal recessive inherited disorder involving the MPO gene located at 17q23. MPO plays a critical role in the microbicidal activity of neutrophils. Activated neutrophils release MPO into the phagolysosomes or the extracellular spaces. MPO, hydrogen peroxide, and chloride ion makeup the cytocidal toxic mediators in infections. A secondary type of MPO deficiency has been observed in patients with clonal hematopoietic disorders, such as myelodysplastic syndrome and acute myeloid leukemia. The MPO deficiency in these patients is often due to discrete chromosomal aberrations involving the MPO gene.

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Acute Myeloid Leukemia—Overview

Faramarz Naeim MD, ... Ryan T. Phan PhD, in Atlas of Hematopathology (Second Edition), 2018

18.2.1 Myeloperoxidase Stain

Myeloperoxidase (MPO) is a lysosomal enzyme present in granulocytic and monocytic cells (Fig. 18.8). MPO is expressed in neutrophilic and eosinophilic lineages in all stages of maturation, but in basophils it is more often detected in the immature forms. The mature basophils are usually negative for MPO. The intensity of MPO staining is less in monocytes than in granulocytes. Erythroid precursors and lymphocytes are MPO negative. A peroxidase isoenzyme has been detected by electron microscopy in the dense tubular system of platelets and megakaryocytes, but, by conventional techniques, these cells are MPO negative.

Figure 18.8. Immunohistochemical (A) and cytochemical (B) stains for MPO demonstrating numerous MPO-positive cells.

MPO activity declines rather rapidly. Air-dried unstained smears should be stored at cool temperature, in the dark, and be used within 1–2 weeks.

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Evaluation of the Patient with Suspected Immunodeficiency

Steven M. Holland, John I. Gallin, in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Eighth Edition), 2015

Myeloperoxidase Deficiency

Myeloperoxidase (MPO, also called verdoperoxidase), the heme-binding protein that makes pus green, catalyzes the conversion of hydrogen peroxide to hypochlorous acid (bleach). MPO deficiency, the most common neutrophil disorder, affects about 1 in 2000 persons but is quite silent in most cases. Neutrophil function is affected by MPO deficiency in a variety of ways. The respiratory burst in MPO-deficient neutrophils is prolonged and, as a result, exaggerated amounts of hydrogen peroxide are produced.71 Phagocytosis is normal to increased in MPO-deficient neutrophils, whereas bactericidal activity is somewhat slower than normal. Killing of Aspergillus conidia by MPO-deficient neutrophils is retarded, whereas the combination of MPO-deficient neutrophils with CGD neutrophils (see “Chronic Granulomatous Disease”), which are unable to generate hydrogen peroxide but do produce MPO, results in normal killing of Aspergillus conidia.72 Pathologic sequelae of MPO deficiency are brought out only in the presence of other impairments of host defense, such as diabetes mellitus. A very few MPO-deficient diabetic patients have had severe yeast infections. The dihydrorhodamine oxidation assay, which is used for CGD diagnosis, can be falsely abnormal in MPO deficiency.73

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Acute leukemias

Reeba A. Omman, Ameet R. Kini, in Rodak's Hematology (Sixth Edition), 2020

Myeloperoxidase

Myeloperoxidase (MPO) (Figures 31.15 and 31.16) is an enzyme found in the primary granules of granulocytic cells (neutrophils, eosinophils, and, to a certain extent, monocytes). Lymphocytes do not exhibit MPO activity. This stain is useful for differentiating the blasts of AML from those of ALL.

Interpretation

MPO is present in the primary granules of most granulocytic cells, beginning at the promyelocyte stage and continuing throughout maturation. Leukemic myeloblasts are usually positive for MPO. In many cases of the AMLs (without maturation, with maturation, and promyelocytic leukemia), it has been found that more than 80% of the blasts show MPO activity. Auer rods found in leukemic blasts and promyelocytes test strongly MPO positive.

In contrast, lymphoblasts in ALL and lymphoid cells are MPO negative. It is important that the reaction only in the blast cells be used as the determining factor for the differentiation of acute leukemias. This is true for MPO and for other cytochemical stains used in determining cell lineage described in this chapter: maturing granulocytes are MPO positive; this is a normal finding and has little or no diagnostic significance.

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Immunodeficiencies

Steven M. Holland, ... Luigi D. Notarangelo, in Infectious Diseases (Fourth Edition), 2017

Myeloperoxidase Deficiency

Myeloperoxidase (MPO; 17q23) is synthesized in neutrophils and monocytes, packaged into primary granules and released either into the phagosome or the extracellular space where it catalyzes the conversion of H2O2 to hypochlorous acid. Myeloperoxidase deficiency (OMIM #254600) is the most common primary phagocyte disorder: 1/4000 individuals have complete MPO deficiency and 1/2000 have a partial defect.25 It is an autosomal recessive trait with variable expressivity. Despite in vitro studies showing that MPO-deficient neutrophils are markedly less efficient than normal neutrophils in killing Candida albicans and hyphal forms of Aspergillus fumigatus, clinical infection in MPO deficiency is rare. Of the MPO-deficient patients who have had clinical findings, candidiasis is the most common problem, and diabetes mellitus appears to be a critical co-factor.25 Definitive diagnosis is established by neutrophil or monocyte peroxidase histochemical staining or specific protein detection. There is no specific treatment for MPO deficiency. Dihydrorhodamine gives an abnormal signal in complete MPO deficiency.20

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Defects of Innate Immunity

Sergio D. Rosenzweig, Steven M. Holland, in Pediatric Allergy: Principles and Practice (Third Edition), 2016

Myeloperoxidase Deficiency

Myeloperoxidase (MPO) deficiency is the most common primary phagocyte disorder. It is an autosomal recessive disease with variable expressivity: 1:4,000 individuals have complete MPO deficiency, and 1:2,000 have a partial defect.70 Myeloperoxidase catalyzes the conversion of H2O2 to hypohalous acid. In those MPO-deficient patients who have had clinical findings, infections caused by different Candida strains were the most common: mucocutaneous, meningeal and bone infections, as well as sepsis, have been described.71–74 Diabetes mellitus appears to be a critical co-factor for Candida infections in the context of MPO deficiency. A definitive diagnosis is established by sequencing of the MPO gene, neutrophil/monocyte peroxidase histochemical staining or specific protein detection. There is no specific treatment for MPO deficiency; diabetes should be sought and controlled, and infections should be treated.

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Inflammation Friend or Foe?

Thomas J. Lewis PhD, Clement L. Trempe MD, in The End of Alzheimer's (Second Edition), 2017

Myeloperoxidase

Myeloperoxidase (MPO) is a peroxidase enzyme. MPO is most abundantly expressed in neutrophil granulocytes (a subtype of white blood cells). It is a lysosomal protein stored in the neutrophil. MPO has a heme (blood like) pigment, which causes its green color in secretions rich in neutrophils (immune cells that can destroy pathogens), such as pus and some forms of mucus.

Recent studies have reported an association between myeloperoxidase levels and the severity of coronary artery disease. It has been suggested that myeloperoxidase plays a significant role in the development of the atherosclerotic lesion and rendering plaques unstable. Again, inflammation is implicated in atherosclerosis and plaque buildup, thus a connection between inflammation and myeloperoxidase clearly exists.

A Cleveland Clinic Foundation 2003 study suggested that MPO could serve as a sensitive predictor for myocardial infarction (heart attack) in patients having chest pain [35]. Since then, there have been over 100 published studies documenting the utility of MPO testing. Most recently, a Canadian group reported that elevated MPO levels more than doubled the risk for cardiovascular mortality over a 13-year period, and measuring both MPO and CRP provided added benefit for risk prediction than just measuring CRP alone [36].

Alzheimer’s, Parkinson’s, and MS all have a MPO connection. In an article by Texas scientists titled, Microglia and myeloperoxidase: A deadly partnership in neurodegenerative disease, the authors reiterate the connection between these diseases and inflammation [37]. “The presence of [MPO] in these diseased brains has been reported by a number of investigators,” they stated. They also believe that MPO is involved in the perpetuation of inflammation and is a likely target for treatment. This has yet to be proven, and MPO should be viewed as a marker for inflammation, rather than a target, pending more definitive research. However, with an association between MPO, cardiovascular disease and Alzheimer’s illuminated, it makes sense to perform both the MPO and CRP tests together, to get a better picture of current or future disease risk. If an MPO and CRP combination test is more instructive compared to a single test, imagine the diagnostic power of combining more of these tests into your health portfolio.

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Cardiac Markers

Amitava Dasgupta PhD, DABCC, Amer Wahed MD, in Clinical Chemistry, Immunology and Laboratory Quality Control, 2014

8.10 Myeloperoxidase

Myeloperoxidase (MPO) is a leukocyte enzyme. Initial studies showed significantly increased MPO levels in patients with angiographically documented coronary artery disease. In patients presenting to the emergency department with chest pain, elevated MPO levels independently predicted increased risk for major adverse cardiac events, including myocardial infarction, reinfarction, need for revascularization, or death at 30 days and at 6 months. Among the patients who presented to the emergency department with chest pain but who were ultimately ruled out for myocardial infarction, an elevated MPO level at presentation predicted subsequent major adverse cardiovascular outcomes. MPO may be a useful early marker in the emergency department based on its ability to detect plaque vulnerability that precedes acute coronary syndrome.

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