Alpha-1 antitrypsin in the blood

Alpha ₁ -antitrypsin is a glycoprotein synthesized by the liver and providing 90% of the activity inhibiting trypsin in the blood. This glycoprotein inhibits the action of not only trypsin, but also chymotrypsin, elastase, kallikrein, cathepsins and other tissue proteases, promoting their breakdown.

Numerous isoforms of this enzyme, encoded by different alleles, have been described. One or two forms of alpha ₁ -antitrypsin can be detected in the blood of one person. The M form is the most common. The formation of the Z form (so called because of its special electrophoretic mobility in the gel) is associated with a gene mutation leading to the replacement of one of the amino acids in the M protein. The Z protein is released from liver cells with difficulty and causes local damage that can lead to hepatitis and cirrhosis. The nephelometry method is used to determine the concentration of alpha _{1 -antitrypsin in the blood serum. The alpha1} -antitrypsin form (ZZ, MM, MZ, FZ) is determined using electrophoresis or molecular genetic methods.

Reference values (norm) for the concentration of alpha ₁ -antitrypsin in blood serum: in adults under 60 years of age 0.78-2 g/l, over 60 years of age - 1.15-2 g/l.

Alpha ₁ -antitrypsin is an acute phase protein, so its content in the blood serum increases in inflammatory processes (acute, subacute and chronic infectious diseases, acute hepatitis and liver cirrhosis in the active phase, necrotic processes, postoperative conditions, recovery phase of thermal burns, vaccination). The content of alpha ₁ -antitrypsin in the blood serum increases in malignant neoplasms: cancer (especially cervical cancer) and metastases, lymphomas (especially lymphogranulomatosis).

Of particular interest are cases of decreased alpha ₁ -antitrypsin concentration in the blood serum. Patients homozygous for the Z allele develop severe liver damage - neonatal hepatitis, liver cirrhosis. Severe alpha ₁ -antitrypsindeficiency is often combined with juvenile basal pulmonary emphysema, early development of emphysema (at the age of 20-40 years). Quite often, latent forms of congenital alpha ₁ -antitrypsin deficiency (MZ phenotype) are observed. Such children are found to have various forms of liver damage, including early cholestasis. Liver cirrhosis develops in 1-2% of patients.

The prevalence of homozygosity for the Z allele is approximately 1:3000. In such cases, the activity of alpha ₁ -antitrypsin in the blood serum is reduced to 10-15% of normal values. Not all individuals homozygous for the Z allele develop lung and liver disease. The risk of developing emphysema is significantly increased in smokers, since cigarette smoke oxidizes the thiol group of the active site in the alpha ₁ -antitrypsin molecule, which reduces the activity of the enzyme, which is present in small quantities. Despite the fact that α ₁ -antitrypsin is an acute phase protein, its concentration in homozygotes for the Z allele never rises above 50% of the lower limit of normal.

In individuals with the MZ form of alpha _1- antitrypsin, its activity in the blood serum is approximately 60% of the norm, so the risk of developing lung diseases in them is significantly lower compared to people homozygous for the Z allele.

Acquired deficiency of alpha ₁ -antitrypsin is observed in nephrotic syndrome, gastroenteropathy with protein loss, acute phase of thermal burns. A decrease in the concentration of alpha ₁ -antitrypsin in the blood is possible in patients with viral hepatitis due to a violation of its synthesis in the liver, as well as in respiratory distress syndrome, acute pancreatitis, coagulopathy due to increased consumption of this glycoprotein.

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