ANCA against MPO and PR3: the pathway in the body

This page shows the biochemical pathway behind the laboratory value MPO and PR3 antibodies (ANCA against myeloperoxidase and proteinase 3): which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

ANCA are autoantibodies against the enzymes myeloperoxidase (MPO) and proteinase 3 (PR3) from neutrophil granulocytes. When they bind to primed cells, they trigger the release of oxygen radicals, proteases and DNA nets.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. Neutrophil granulocyte → MPO and PR3 Myeloperoxidase (MPO) and proteinase 3 (PR3) are made during maturation and stored in granules inside the cell. Source 3, 4↕ both, depending on amount MPO makes germ-killing hypochlorous acid and PR3 cleaves proteins of pathogens and activates messengers; the same tools also alter the body's own proteins. established physiology Source 3, 4
   ⚖ When the balance tips

   too much — If many granules are emptied, MPO and PR3 also act outside the cell until inhibitors in the blood such as alpha-1 antitrypsin capture PR3.

   too little — If there is little MPO in the cells, neutrophils kill some fungi more slowly; other defence routes cover part of the task.

   established physiology · Source 3, 4

2. MPO and PR3 → MPO and PR3 outside · TNF-α, C5a Messengers such as TNF-α or the complement fragment C5a put neutrophils on standby. In the process MPO and PR3 reach the cell surface. Source 1, 6↕ both, depending on amount At the surface MPO and PR3 can act immediately but are also accessible to antibodies there; some neutrophils carry PR3 on the outside even at rest. observed in studies Source 1, 6
   ⚖ When the balance tips

   too much — If many neutrophils are primed, more MPO and PR3 lie outside and more binding sites for ANCA are available.

   too little — If the cells are at rest, MPO and PR3 stay mostly inside and ANCA find hardly any binding sites.

   observed in studies · Source 1, 6

3. MPO and PR3 outside → ANCA bound · ANCA (IgG) ANCA are autoantibodies against MPO or PR3. They bind with one end to the enzyme on the cell; their other end points outwards. Source 1, 2↓ depletes Bound ANCA fully activate the primed cell without any germ being present; in cell experiments and animal models they thereby release radicals and enzymes. observed in studies Source 1
   ⚖ When the balance tips

   too much — If many ANCA bind, more neutrophils are activated, stick to the vessel wall and release radicals and proteases there.

   too little — If few or no ANCA bind, neutrophil activation follows only the signals from germs and tissue.

   observed in studies · Source 1, 2

   Field of research — ANCA against MPO and PR3 are studied in inflammatory disorders of small blood vessels. Source 1, 2

4. Fcγ receptors → Oxygen radicals NADPH oxidase NADPH oxidase transfers electrons to oxygen, producing superoxide and from it hydrogen peroxide. Source 3↓ depletes Superoxide and hydrogen peroxide damage germs and are also the starting material from which MPO makes even stronger oxidants. established physiology Source 3
   ⚖ When the balance tips

   too much — If a lot of it forms outside a germ, it oxidises proteins and fats of the surrounding tissue.

   too little — If little forms, MPO lacks its starting material and germs are killed more slowly.

   established physiology · Source 3

5. Oxygen radicals → Hypochlorous acid MPO · chloride MPO converts hydrogen peroxide with chloride into hypochlorous acid, the active substance of bleach. Its iron haem centre makes this possible. Source 3↓ depletes Hypochlorous acid oxidises proteins and fats of bacteria and fungi; taurine captures it and forms a milder chloramine. established physiology Source 3
   ⚖ When the balance tips

   too much — If a lot of hypochlorous acid forms outside the cell, it also alters the body's own proteins and lipoproteins.

   too little — If little forms, neutrophils kill some germs more slowly while other routes continue.

   established physiology · Source 3

6. Fcγ receptors → Granules emptied The granules fuse with the cell membrane and release PR3, elastase and MPO to the outside. Source 4, 1↕ both, depending on amount Released proteases break down pathogen proteins and tissue components such as elastin; inhibitors in the blood limit their action to the immediate surroundings. observed in studies Source 4
   ⚖ When the balance tips

   too much — If many granules are emptied, the amount of protease exceeds the local inhibitors, and tissue of the vessel wall is cleaved.

   too little — If few are emptied, the inhibitors in the blood quickly capture the proteases.

   observed in studies · Source 4, 1

7. Fcγ receptors → NETs Activated neutrophils can cast out nets made of their DNA, to which MPO and PR3 cling. They trap germs. Source 5↕ both, depending on amount The nets hold germs and kill them; at the same time they present MPO and PR3 to the immune system, which can further stimulate ANCA formation. observed in studies Source 5
   ⚖ When the balance tips

   too much — If many nets are formed and broken down slowly, MPO and PR3 remain visible to the immune system for longer.

   too little — If few are formed, neutrophils trap fewer germs outside the cell.

   observed in studies · Source 5

Further stations

• Neutrophil granulocyte — most common white blood cell Neutrophil granulocytes form in the bone marrow and are the first immune cells at the site of an infection. They live only a few days. Source 2, 4↑ supplies Neutrophils engulf bacteria and fungi and kill them with oxygen radicals and enzymes from their granules. established physiology Source 3, 4
  ⚖ When the balance tips

  too much — If many neutrophils are active, more of their enzymes and radicals also reach the surrounding tissue.

  too little — If few neutrophils are present, invading germs are cleared more slowly.

  established physiology · Source 4

• Fcγ receptors — are cross-linked The free end of ANCA binds to Fcγ receptors on the same or a neighbouring cell. The cross-linking triggers signals inside the cell. Source 1↑ supplies The signals from the cross-linked receptors switch on NADPH oxidase, make granules release their contents and promote adhesion to vessel walls. observed in studies Source 1
  ⚖ When the balance tips

  too much — If many receptors are cross-linked, the cell's response is strong and sustained.

  too little — If few are cross-linked, the cell stays on standby without releasing its weapons.

  observed in studies · Source 1

Cofactors in this pathway

• Iron — Haem iron in the active site of MPO, which converts hydrogen peroxide with chloride Source 3In the ORY catalogue as a laboratory value: Eisen
• Taurine — Captures hypochlorous acid and forms the milder taurine chloramine Source 3In the ORY catalogue as a laboratory value: Taurin
• Chloride — Is converted by MPO together with hydrogen peroxide into hypochlorous acid Source 3
• NADPH — Supplies NADPH oxidase with the electrons for making superoxide Source 3
• Hydrogen peroxide — Starting material that MPO converts into hypochlorous acid Source 3

Sources

1. Jennette JC, Falk RJ. Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol 2014 · PubMed 25003769
2. Kitching AR, Anders HJ, Basu N et al. ANCA-associated vasculitis. Nat Rev Dis Primers 2020 · PubMed 32855422
3. Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukoc Biol 2005 · PubMed 15689384
4. Korkmaz B, Moreau T, Gauthier F. Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions. Biochimie 2008 · PubMed 18021746
5. Kessenbrock K, Krumbholz M, Schönermarck U et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med 2009 · PubMed 19448636
6. Csernok E, Ernst M, Schmitt W et al. Activated neutrophils express proteinase 3 on their plasma membrane in vitro and in vivo. Clin Exp Immunol 1994 · PubMed 8306499

Related pathways

• Granulocytes in the gut wall — granules emptied
• CRP — fcγ receptors
• Cholesterol and lipoproteins — Eisen, Taurin

As of 2026-10-05. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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