MPO gene

The MPO gene (MPO stands for: myeloperoxidase) is a protein-coding gene located on chromosome 17q22.

Diseases associated with MPO include:

• myeloperoxidase deficiency
• and
• Alzheimer's disease, familial

• MPO mutations, especially those leading to complete MPO deficiency, are cumulatively associated with GPP (generalized pustular psoriasis) (Haskamp S et al. 2020). The activity of four proteases previously thought to be activating enzymes of IL-36 precursors correlated with MPO deficiency. MPO and the affected signaling pathways could represent attractive targets for the resolution of inflammation in neutrophils (Haskamp S et al. 2020).

Myeloperoxidase (MPO) is a heme protein synthesized during myeloid differentiation and is the major component of neutrophil azurophil granules. Myeloperoxidase is produced as a single-chain precursor and is subsequently cleaved into a light chain and a heavy chain. Mature myeloperoxidase is a tetramer consisting of 2 light and 2 heavy chains. This enzyme produces acids that are central to the microbicidal activity of neutrophils. Thus, myeloperoxidase is part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In stimulated polymorphonuclear leukocytes, MPO catalyzes the production of hypochlorous acid (hypochlorous acid (HOCl) is a mild acid naturally produced in the white blood cells of all mammals. It plays an important role in our immune system e.g. in incipient infections) which significantly increases the microbicidal activity of polymorphonuclear leukocytes. Mediates proteolytic cleavage of alpha-1 microglobulin to form t-alpha-1 microglobulin, which effectively inhibits oxidation of low-density lipoprotein particles and limits vascular damage.

1. Cech P et al (1979) Leukocyte myeloperoxidase deficiency and diabetes mellitus associated with Candida albicans liver abscess. Am J Med 66: 149-153
2. Cramer R et al (1982) Incidence of myeloperoxidase deficiency in an area of northern Italy: histochemical, biochemical and functional studies. Brit J Haemat 51: 81-87
3. DeLeo FR et al (1998) A novel form of hereditary myeloperoxidase deficiency linked to endoplasmic reticulum/proteasome degradation. J Clin Invest 101: 2900-2909.
4. Fujisawa T et al (2015) Granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis: Therapeutic Outcomes in Three Refractory Patients. Ther Apher Dial 19:336-341.

5. Haskamp S et al (2020) Myeloperoxidase Modulates Inflammation in Generalized Pustular Psoriasis and Additional Rare Pustular Skin Diseases. Am J Hum Genet 107:527-538. d

6. Mizutani Y et al (2020) Intensive granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis. J Dermatol 47:1326-1329.
7. Takeichi T et al. (2023) Mild generalised pustular psoriasis patient with a heterozygous hypomorphic MPO variant successfully treated with granulocyte and monocyte adsorption apheresis. Exp Dermatol 32:1557-1562.