ACE2- und GM-CSF-Autoantikörper: the pathway in the body

ACE2- und GM-CSF-Autoantikörper is part of the pathway “ACE2 and GM-CSF autoantibodies”. This page shows the whole pathway; the station of ACE2- und GM-CSF-Autoantikörper is highlighted.

Where this laboratory value sits: Autoantibody binds — to GM-CSF or ACE2. The autoantibody attaches to its target. Against GM-CSF it blocks binding to the receptor; against ACE2 it can lower the enzyme activity. Source 6, 8

In brief

ACE2 and GM-CSF autoantibodies are antibodies against one of the body's own enzymes and one of its messengers. If they bind to a functional site, they capture GM-CSF before it reaches its receptor or damp the cleavage of angiotensin II by ACE2.

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. Autoreactive B cell → Plasma cell · T-cell help If the B cell receives help from T cells, it matures into a plasma cell. This releases large amounts of a single antibody into the blood, some for years. Source 2↑ supplies Plasma cells are antibody factories; long-lived plasma cells in the bone marrow maintain the level of an antibody without new stimulation. established physiology Source 2
   ⚖ When the balance tips

   too much — If many plasma cells form against the same protein, the level of the autoantibody in the blood rises.

   too little — If the plasma cells die off, the level falls with the antibody's half-life of a few weeks.

   established physiology · Source 2

2. Plasma cell → IgG autoantibody The autoantibody is usually of the IgG type. It recognises a particular site on GM-CSF or on ACE2 and circulates through the body with the blood. Source 3, 8↓ depletes If the autoantibody binds to a functional site, it occupies it; other autoantibodies bind without any detectable effect. observed in studies Source 3
   ⚖ When the balance tips

   too much — If there is a lot of neutralising autoantibody in the blood, much of the target molecule is captured before it reaches its receptor.

   too little — If there is little of it in the blood, most of the target molecule stays free and its action hardly changes.

   observed in studies · Source 3, 6

3. GM-CSF → GM-CSF receptor GM-CSF binds to its receptor on the phagocytes of the air sacs. The receptor passes the signal into the cell via JAK2 and STAT5. Source 4, 5↑ supplies The loaded receptor switches on the factor PU.1 in the phagocyte, which controls its maturation programme. established physiology Source 4
   ⚖ When the balance tips

   too much — Once all receptors are occupied, further GM-CSF brings no stronger signal.

   too little — If the receptors stay empty because GM-CSF is captured, no signal reaches the cell.

   established physiology · Source 4

4. GM-CSF receptor → PU.1 in the nucleus JAK2, STAT5 PU.1 switches on genes in the phagocytes of the air sacs that let them mature and equip them for fat breakdown and defence. Source 4, 5↑ supplies Through PU.1 the phagocytes gain the ability to absorb and break down surfactant and to remove germs. established physiology Source 4
   ⚖ When the balance tips

   too much — If PU.1 is highly active, the phagocytes mature fully and break down surfactant briskly.

   too little — If PU.1 is barely active, the cells remain immature; fat breakdown and defence against germs run more slowly.

   established physiology · Source 4

5. PU.1 in the nucleus → Surfactant breakdown Surfactant is a film of fats and proteins that keeps the air sacs open. Mature phagocytes absorb used surfactant and break it down. Source 5, 4↕ both, depending on amount Formation and breakdown of surfactant balance each other; this keeps the film thin enough for gas exchange. established physiology Source 5
   ⚖ When the balance tips

   too much — If a lot of surfactant is broken down, the film stays thin; production by the cells of the air sacs keeps it in balance.

   too little — If little is broken down, for example when neutralising autoantibodies capture GM-CSF, surfactant accumulates in the air sacs.

   observed in studies · Source 5, 6

6. Angiotensin II → Angiotensin-(1-7) ACE2 · zinc The enzyme ACE2 has zinc in its active site and cleaves one amino acid from angiotensin II. This produces angiotensin-(1-7). Source 7, 9↑ supplies Angiotensin-(1-7) binds to the Mas receptor and counteracts angiotensin II there: vessels widen and inflammatory and scarring signals are damped. established physiology Source 7
   ⚖ When the balance tips

   too much — If a lot of angiotensin-(1-7) forms, the vessel-widening side of the system predominates.

   too little — If ACE2 activity falls, for example through binding autoantibodies, less angiotensin-(1-7) forms and the balance shifts towards the angiotensin II side.

   observed in studies · Source 7, 8

7. Angiotensin II → AT1 receptor At the AT1 receptor, angiotensin II constricts vessels, causes salt to be retained and stimulates inflammatory and growth signals. Source 7↕ both, depending on amount In the short term the AT1 receptor maintains blood pressure; when strongly stimulated for long periods, it drives inflammation and tissue remodelling. established physiology Source 7
   ⚖ When the balance tips

   too much — If the receptor is heavily occupied, vessels stay narrower and salt and water are retained.

   too little — If it is lightly occupied, the vessels relax and the kidneys excrete more salt.

   established physiology · Source 7

8. Angiotensin-(1-7) → Mas receptor Angiotensin-(1-7) binds to the Mas receptor. In vessels this releases nitric oxide, which relaxes the vessel wall. Source 7↑ supplies Via the Mas receptor, angiotensin-(1-7) acts as a counterweight to the AT1 pathway; in animal models it damps inflammation and scarring. observed in studies Source 7
   ⚖ When the balance tips

   too much — If the Mas receptor is strongly stimulated, vessels relax and the action of angiotensin II is offset.

   too little — If little angiotensin-(1-7) arrives, this counterweight is missing and the AT1 pathway acts more strongly.

   observed in studies · Source 7

Further stations

• Autoreactive B cell — recognises a body protein B cells that recognise the body's own proteins are normally weeded out or reprogrammed in the bone marrow. A few escape this control. Source 1↕ both, depending on amount A certain number of weakly autoreactive B cells is part of the normal repertoire; only when they are activated do they make antibodies against the body's own protein. established physiology Source 1
  ⚖ When the balance tips

  too much — If more autoreactive B cells escape control, the number of cells that can make autoantibodies with suitable help increases.

  too little — If autoreactive B cells are effectively weeded out, hardly any autoantibodies against this protein form.

  established physiology · Source 1

• Autoantibody binds — to GM-CSF or ACE2 The autoantibody attaches to its target. Against GM-CSF it blocks binding to the receptor; against ACE2 it can lower the enzyme activity. Source 6, 8↓ depletes Neutralising autoantibodies deprive the body of the action of one of its own messengers or enzymes; detection alone does not show whether an antibody neutralises. observed in studies Source 6, 8
  ⚖ When the balance tips

  too much — If much is bound, little reaches the target: GM-CSF hardly reaches its receptor, and soluble ACE2 showed lower activity in one study.

  too little — If little is bound, GM-CSF and ACE2 act largely as they would without autoantibodies.

  observed in studies · Source 6, 8

  Field of research — Autoantibodies against GM-CSF are studied in lung disorders, those against ACE2 after SARS-CoV-2 infections. Source 6, 8

• GM-CSF — messenger GM-CSF is a messenger produced by T cells and cells of the air sacs, among others. It acts on phagocytes. Source 4↑ supplies In the lung, GM-CSF is the signal that lets the phagocytes of the air sacs mature and work. established physiology Source 4
  ⚖ When the balance tips

  too much — If a lot of GM-CSF is present, more phagocytes and granulocytes are formed and activated.

  too little — If little GM-CSF reaches the receptor, the phagocytes of the air sacs remain immature.

  established physiology · Source 4

• Angiotensin II — constricts vessels Angiotensin II is a messenger of the renin-angiotensin system, which controls blood pressure and salt balance. ACE2 breaks it down. Source 7↕ both, depending on amount Angiotensin II maintains blood pressure via its AT1 receptor; at the same time it is the starting material from which ACE2 makes angiotensin-(1-7), which acts in the opposite way. established physiology Source 7
  ⚖ When the balance tips

  too much — If angiotensin II builds up, for example because ACE2 is less active, more of it remains at the AT1 receptor.

  too little — If little angiotensin II is present, less angiotensin-(1-7) is formed as well.

  established physiology · Source 7

Cofactors in this pathway

• Zinc — Sits in the active site of ACE2, which cleaves angiotensin II to angiotensin-(1-7) Source 9In the ORY catalogue as a laboratory value: Zink
• Tryptophan — In the gut, ACE2 helps a transporter absorb tryptophan and other amino acids Source 10In the ORY catalogue as a laboratory value: Tryptophan
• Cholesterol — Component of surfactant, which mature lung phagocytes absorb and break down Source 5In the ORY catalogue as a laboratory value: Cholesterin / Fettstoffwechsel
• Phosphatidylcholine — Main component of the surfactant film in the air sacs Source 5
• Angiotensin II — Starting material that ACE2 converts to angiotensin-(1-7) Source 7

Sources

1. Nemazee D. Mechanisms of central tolerance for B cells. Nat Rev Immunol 2017 · PubMed 28368006
2. Nutt SL, Hodgkin PD, Tarlinton DM, Corcoran LM. The generation of antibody-secreting plasma cells. Nat Rev Immunol 2015 · PubMed 25698678
3. Ku CL, Chi CY, von Bernuth H et al. Autoantibodies against cytokines: phenocopies of primary immunodeficiencies? Hum Genet 2020 · PubMed 32419033
4. Trapnell BC, Whitsett JA. Gm-CSF regulates pulmonary surfactant homeostasis and alveolar macrophage-mediated innate host defense. Annu Rev Physiol 2002 · PubMed 11826288
5. Trapnell BC, Nakata K, Bonella F et al. Pulmonary alveolar proteinosis. Nat Rev Dis Primers 2019 · PubMed 30846703
6. Ataya A, Knight V, Carey BC et al. The Role of GM-CSF Autoantibodies in Infection and Autoimmune Pulmonary Alveolar Proteinosis: A Concise Review. Front Immunol 2021 · PubMed 34880857
7. Santos RAS, Sampaio WO, Alzamora AC et al. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). Physiol Rev 2018 · PubMed 29351514
8. Arthur JM, Forrest JC, Boehme KW et al. Development of ACE2 autoantibodies after SARS-CoV-2 infection. PLoS One 2021 · PubMed 34478478
9. Hooper NM, Lambert DW, Turner AJ. Discovery and characterization of ACE2 - a 20-year journey of surprises from vasopeptidase to COVID-19. Clin Sci (Lond) 2020 · PubMed 32990314
10. Hashimoto T, Perlot T, Rehman A et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 2012 · PubMed 22837003

Whole pathway: ACE2 and GM-CSF autoantibodies

Related pathways

• ASCA and ANCA — plasma cell
• IgG antibodies to food — plasma cell
• Secretory IgA — plasma cell
• Cortisol — Zink, Cholesterin / Fettstoffwechsel
• Progesterone — Zink, Cholesterin / Fettstoffwechsel

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