alpha-1-antitrypsin (α1-antitrypsin or AAT)

Sample

• The patient needs to fast for several hours before giving the sample.
• This test is done in the serum or plasma.
  • Separate serum immediately and store properly.
• Take 3 to 5 ml of blood in the disposable syringe. Keep the syringe for 15 to 30 minutes and then centrifuge for 2 to 4 minutes. In this way can get a clear serum.
• Serum or plasma is stable for ≥ 7 days at 4 °C.
  • At -70 °C is stable for 3 months.

Purpose of the test (Indications)

1. This helps in the diagnosis of juvenile and adult cirrhosis of the liver.
2. For neonatal respiratory distress syndrome.
3. For emphysema (there is a deficiency or absence of this enzyme).
4. This is useful for the diagnosis of familial chronic obstructive lung disease.
5. This enzyme may be deficient in protein-losing disorder.
6. This is also an acute-phase protein, raised in inflammation, infections, and malignancy.

Precautions

1. This is raised during pregnancy.
2. Oral contraceptives increase the level of AAT.

Pathophysiology

1. This is present in the alpha globulin fraction and mainly consists of the glycoprotein.
   1. AAT is a relatively small size and can diffuse into the tissues and is important in the prevention of loss of elastic recoil.
   2. The deficiency of AAT or excess of elastase in the case of uninhibited elastase in the bronchial tree leads to emphysema.

2. This is the most potent protein (AAT) which inhibits proteolytic enzymes produced by neutrophils during inflammation When produced during phagocytosis by the neutrophils.
   1. This is an α-1 proteinase inhibitor.
   2. AAT is the highest concentration proteinase inhibitor in the plasma on a molar basis.
   3. This enzyme reacts with elastin in the tracheobronchial system and the vascular endothelium.
3. This is synthesized in the liver by hepatocytes.
   1. Catabolism also takes by the liver parenchymal cells. This takes two routes:
      1. AAT -protease complex is removed by the serpin-enzyme complex receptor.
      2. Desialylated AAT is removed by the asialoglycoprotein receptors.
4. It breaks enzymes like Trypsin, Chymotrypsin, Elastase, Thrombin, and Plasmin.

5. Its level rises non-specifically in acute inflammations, severe infections, and necrosis.

6. Deficiency α1-Antitrypsin of maybe:
   1. Genetic.
   2. Acquired.
7. Its deficiency gives rise to lung and liver diseases.
8. This enzyme protects the lungs.

9. Acquired deficiency may be seen in protein deficiency like malnutrition, liver diseases, Nephrotic syndrome, neonatal respiratory distress syndrome.
10. People with a1a deficiency develop emphysema in the 3rd or 4th decades of life.
11. Congenital deficiency of ATT results in premature emphysema.
    1. In inherited AAT deficiency is associated with symptoms in early life than the acquired AAT deficiency.
    2. Inherited AAT deficiency is associated with liver and biliary diseases.
    3. Homozygous people have severe pulmonary and liver disease very early in life.
    4. 5 to 14% of the adult population is in the heterozygous state and are considered to be at greater risk for the development of emphysema.
12. Chronic bronchitis is prominent with a1a deficiency who smoke.
    1. Cigarettes smoking and other volatile irritants stimulate the release of enzymes from the white blood cells in the lung.
    2. Without the presence of ATT, these above enzymes cause the destruction of the lung parenchyma.
    3. There will be severe emphysema and usually seen in the 3rd or 4th decades.
13. This is a positive acute-phase protein.

Alpha 1- antitrypsin deficiency:

1. This enzyme deficiency is an inherited disorder that gives rise to liver and lung diseases.
   1. There are 75 known genetic variants of AAT associated with deficiency.
   2. The most common phenotype is Pi MM and deficiency of AAT are Pi ZZ and SZ.
2. The congenital decrease may cause the early onset of emphysema or infantile hepatitis and ultimately lead to cirrhosis.
3. This is inherited as an autosomal codominant.
4.  There is a mutation in the gene SERPINA1.
5. There are two common diseases like emphysema and liver cirrhosis.
   1. This is also seen in liver diseases like:
      1. Neonatal cholestasis or hepatitis are common at the age of 3 to 8 weeks and regress after a few weeks.
         1. Differentiation from the biliary atresia is very important.
         2. Because there is very high mortality if surgery was done in the patients with Pi ZZ infants.
      2. Cirrhosis.
      3. Hepatocellular carcinoma.

Sign and symptom of Deficiency of α1-Antitrypsin:

• There is tiredness.
• Patients have shortness of breath and wheezing.
• The patient will have repeated episodes of lung infection.
• There may be a vision problem.
• There is weight loss.
• The patient may have tachycardia on standing.
• 10 % of the infants develop liver disease and leads to the yellowness of the skin and eyes are white.
• 15 % of adults have liver damage and develop cirrhosis.

Diagnosis of alpha-1- antitrypsin deficiency:

1. This disease can be diagnosed:
   1. Estimation of a1-antitrypsin in the blood.
   2. Genetic analysis (Genotype or phenotype of the blood).
   3. A sample of DNA from the mouth cell to detect α1-antitrypsin.

Normal

Newborn	145 to 270 mg/dL
Adult	78 to 200 mg/dL
>60 years	115 to 200 mg/dL

Source 2

• Normal = 85 to 213 mg/dL (0.85 to 2.13 g/L).

Critical value for deficiency = around 35 mg/dL

Lab Diagnosis

• The routine serum protein electrophoresis is a good screening test for AAT deficiency.
  • 90% of the AAT is in the α1-globulin portion.

The raised level is seen in:

1. Inflammatory disorders.
2. Cancers.
3. Hormonal effects.
4. Systemic lupus erythematosus.
5. Brain infarction.
6. Hashimoto’s thyroiditis.

The decreased level is seen in:

1. Kidney diseases like Nephrotic syndrome.
2. Prematurity.
3. Liver diseases like acute hepatitis.
4. In lung as respiratory distress syndrome and Emphysema.
5. Protein-losing gastro- enteropathies.
6. Pancreatitis.
7. Congenital defects.
8. AAT levels are  secondarily low in patients like:
   1. Neonatal respiratory distress syndrome.
   2. Severe pancreatitis.
   3. Protein-losing disorders.

 

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