MPO and PR3 antibodies (ANCA against myeloperoxidase and proteinase 3)

Myeloperoxidase (MPO) and proteinase 3 (PR3, listed in the catalogue as “Protease 3”) are enzymes from the granules of neutrophil granulocytes, the most common white blood cells. If the immune system forms antibodies against them, they are called classic ANCA (anti-neutrophil cytoplasmic antibodies). They are measured in serum, in the test catalogue as part of the CFS and PCS autoantibody screens; the blood sample is taken in a practice. The atypical ANCA found in gut inflammation are explained on their own page.

What MPO and proteinase 3 do in the body

Neutrophil granulocytes are the first immune cells at the site of an infection. Myeloperoxidase makes hypochlorous acid – essentially a bleach – from hydrogen peroxide and chloride, which is used to kill ingested bacteria and fungi. Proteinase 3 is a protein-splitting enzyme that breaks down components of pathogens and activates inflammatory messengers. Both normally sit inside the cell. However, when neutrophils are primed by inflammatory signals, MPO and PR3 also reach the cell surface and the nets of genetic material and enzymes that neutrophils cast out to trap pathogens.

MPO and PR3 antibodies negative – what does it mean?

A negative result is the normal case: the immune system has not formed measurable antibodies against these two enzymes. There is thus no indication of ANCA-mediated inflammation of the small blood vessels. Such vessel inflammation cannot be ruled out completely, however, as a small proportion of those affected have no detectable ANCA. This part of the report says nothing about the atypical ANCA in chronic gut inflammation or about the other autoantibodies in the screen.

MPO and PR3 antibodies detected – what happens in the body?

When antibodies bind to MPO or PR3 on the surface of primed neutrophils, these cells are stimulated further: they attach to the inner wall of the vessels, release aggressive oxygen compounds and enzymes and thereby damage the wall of small blood vessels. This can lead to ANCA-associated vessel inflammation (vasculitis), which mainly affects the kidneys, lungs, sinuses, skin and nerves; PR3 antibodies are found more often in granulomatosis with polyangiitis, MPO antibodies in microscopic polyangiitis. Positive results also occur with infections and with certain medicines. After COVID-19 and in ME/CFS, studies have observed various autoantibodies; what role MPO and PR3 antibodies play in this has not been clarified.

The interpretation is given in your report.