ACE2 and GM-CSF autoantibodies

ACE2 and GM-CSF autoantibodies are defence substances directed against two of the body's own proteins: the enzyme ACE2 (angiotensin-converting enzyme 2) and the messenger GM-CSF (granulocyte-macrophage colony-stimulating factor). They are measured in serum. In the test catalogue they appear in the CFS and PCS autoantibody screens, together with antibodies against prothrombin, β2-glycoprotein I, MPO, proteinase 3, the thyroid and IL-6. The background is the observation from studies that, after COVID-19 and in ME/CFS, autoantibodies against messengers, receptors and enzymes may occur more often. Whether they cause symptoms or are a side effect of the immune response is the subject of ongoing research.

What ACE2 does in the body

ACE2 sits on the surface of many cells, for example in the lungs, vessel walls, heart, kidney and gut; part of it circulates dissolved in the blood. The enzyme is a counterweight in the renin-angiotensin system, which controls blood pressure and fluid balance: it converts the vessel-narrowing angiotensin II into angiotensin-(1–7), which widens the vessels and dampens inflammation and scarring processes. In the gut, ACE2 is also involved in the uptake of certain amino acids such as tryptophan. ACE2 became known as the docking site through which SARS-CoV-2 enters cells. When the virus binds, ACE2 is partly removed from the cell surface.

What GM-CSF does in the body

GM-CSF is a messenger of the immune system produced, among others, by T cells, vessel cells and lung cells. It stimulates the formation of granulocytes and monocytes in the bone marrow and controls the maturation and work of scavenger cells (macrophages). It is especially important for the macrophages in the air sacs of the lungs: there they continuously clear away surfactant, a fat-rich film that keeps the air sacs open, and remove inhaled germs. During inflammation the amount of GM-CSF rises; the messenger then amplifies the immune response. Too much is linked with excessive inflammation, too little weakens defences in the lungs.

ACE2 or GM-CSF autoantibodies detected – what happens in the body?

Antibodies against ACE2 have been found in studies after COVID-19 and were associated there with lower activity of dissolved ACE2 in the blood. The idea behind this: if ACE2 is blocked, more angiotensin II remains active – with narrower vessels, more inflammatory signals and altered blood flow; however, this link has not been proven for long/post-COVID. Antibodies against GM-CSF can neutralise the messenger. It is well established that in high amounts this paralyses the macrophages of the lungs: surfactant accumulates in the air sacs (alveolar proteinosis), and certain germs are fought off less well. What role lower amounts play in long/post-COVID and ME/CFS is debated.

No ACE2 and GM-CSF autoantibodies detected – what does it mean?

If no antibodies against ACE2 and GM-CSF are found, this is the normal case. It speaks against these two autoantibodies weakening the effect of ACE2 or GM-CSF at the time of the blood sample. The result says nothing about other possible causes of persistent symptoms. Autoantibodies can arise over time and disappear again; a single finding is therefore a snapshot. In the screen, the result is considered together with the other autoantibodies – for example against prothrombin, β2-glycoprotein I and IL-6 – and with values such as the reactivation of herpes viruses, which are also investigated in long/post-COVID.

The interpretation is given in your report.