Myeloperoxidase deficiency is a disorder featuring lack in either the quantity or the function of myeloperoxidase–an iron-containing protein expressed primarily in neutrophil granules. There are two types of myeloperoxidase deficiency: primary/inherited and secondary/acquired. Lack of functional myeloperoxidase leads to less efficient killing of intracellular pathogens, particularly Candida albicans, as well as less efficient production and release of neutrophil extracellular traps (NETs) from the neutrophils to trap and kill extracellular pathogens. Despite these characteristics, more than 95% of individuals with myeloperoxidase deficiency experience no symptoms in their lifetime. For those who do experience symptoms, the most common symptom is frequent infections by Candida albicans. Individuals with myeloperoxidase deficiency also experience higher rates of chronic inflammatory conditions. Myeloperoxidase deficiency is diagnosed using flow cytometry or cytochemical stains. There is no treatment for myeloperoxidase deficiency itself. Rather, in the rare cases that individuals experience symptoms, these infections should be treated. Pathophysiology
The innate immune system responds quickly to infection, with neutrophils (a type of white blood cells) being the first responders. Neutrophils enter the site of infection and begin to phagocytose (take up) pathogens. Once engulfed, the neutrophils must then degrade the captured pathogens–a process known as intracellular killing.One method of intracellular killing which takes place in the phagolysosomes of neutrophils involves the reaction of myeloperoxidase with hydrogen peroxide (H2O2) acquired in the cells from NADPH oxidase through the respiratory bursts. This reaction generates several acidic products including hypochlorous acid (HClO), which can break down pathogens.
Bacteria such as Pseudomonas aeruginosa and fungi such as Candida albicans are killed in this manner.Neutrophils are also involved in killing extracellular pathogens (pathogens outside of the cell) through the release of NETs. These NETs contain myeloperoxidase, among other antimicrobial proteins. Once released outside of the cell, NETs trap pathogens and may in some cases kill them. Although myeloperoxidase is not required for all NET formation/release, NETs are only formed and released in response to Candida albicans when myeloperoxidase is present. Myeloperoxidase proteins in NETs can still react with H2O2 to form HClO and break down some extracellular pathogens. In myeloperoxidase deficient individuals, this extracellular pathogen killing doesn’t typically occur.Finally, during infection, neutrophils can migrate to the lymph nodes, where they deposit myeloperoxidase. Although the mechanisms of this process aren’t well understood, there is evidence that this extracellular myeloperoxidase interacts with dendritic cells (cells of the adaptive immune system) in the lymph nodes, leading to a decrease in adaptive immune system activity in response to infection. Presentation
About 1:1,000 to 1:4,000 individuals in the United States and Europe and 1:55,000 individuals in Japan experience myeloperoxidase deficiency. The most common symptom of myeloperoxidase deficiency is frequent infections, particularly by the fungus Candida albicans. This symptom is especially frequent in individuals who also experience diabetes mellitus.The majority of myeloperoxidase-deficient individuals, however, do not display any significant tendencies towards chronic infections from most bacteria.