What happens in Alpha-1-antitrypsin deficiency?

Alpha-1-antitrypsin works through two different systems. – One is the adhesion of the defective alpha-1-antitrypsin to the site of origin. The defective protein accumulates in the liver and the liver can no longer adequately perform its other tasks.

In newborns, this can lead to severe liver damage, cirrhosis of the liver. Those affected are often dependent on a donor organ. Cirrhosis of the liver can lead to liver cancer in addition to the loss of liver function.

The consequence of this aggregation in the liver cells is a deficiency of alpha-1-antitrypsin in the rest of the body. This is the second cause of symptoms in the genetic disease. Normally, alpha-1-antitrypsin inhibits elastase, trypsin, chymotrypsin, thrombin and plasmin.

Overactivity of these enzymes has many consequences. An increased amount of elastase leads to a breakdown of elastin in the alveoli, which destroys them and the person affected develops emphysema. Those affected are therefore often wrongly diagnosed with chronic bronchitis. Treatment consists of replacement therapy with alpha-1-antitrypsin and treatment of the symptoms. Liver damage occurs in only about twenty percent of those affected, while lung damage is always present after a longer course of the disease.

Causes for an increase in the antitrypsin level

Elevated levels of alpha-1-antitrypsin in blood or stool can have various causes. Not all causes can be considered pathological. An increase is therefore usually an acute change and not, like the deficiency, genetically caused.

The changes are variable and usually disappear on their own. – During pregnancy women often have higher alpha-1-antitrypsin levels because of the hormonal changes. – Similarly, an artificial hormone change as part of an estrogen therapy can also lead to an increase.

An increase in the alpha-1-antitrypsin level in the stool shows a permeability of the intestinal mucosa. This may indicate allergies or gluten intolerance or may occur in the context of acute or chronic intestinal inflammation. – In the blood, the alpha-1-antitrypsin level increases during inflammation in the body as part of the acute phase reaction. – Alpha-1-antitrypsin also rises in tumour diseases, especially in bronchial carcinomas. Here, alpha-1-antitrypsin can be used as a tumor marker in long-term control.

Alpha-1-antitrypsin in stool

The non-specific protease inhibitor alpha-1-antitrypsin is found in the blood of all humans. In inflammatory reactions, alpha-1-antitrypsin is present in increased quantities. If the intestinal mucosa is permeable, a loss of alpha-1-antitrypsin can occur there and alpha-1-antitrypsin can be detected in the stool.

In this way, the quality of the intestinal mucosa can be controlled without biopsies or other invasive measures. Such damage to the intestinal mucosa can have various causes. Elevated values are possible with allergic reactions and gluten intolerance.

Elevated values are also possible in chronic inflammations of the intestine, such as ulcerative colitis or Crohn’s disease. Alpha-1-antitrypsin is also detectable in acute cases of intestinal inflammation. However, due to diarrhoea, a dilution of the stool can mean false low values.

In chronic intestinal inflammation, alpha-1-antitrypsin can be used for long-term control of the disease. The normal range of alpha-1-antitrypsin is below 0.27mg per gram of stool. In some cases, the loss via the stool can also lead to deficiency symptoms in the rest of the body.