Alpha 1 Anti Trypsin

Alpha-1 antitrypsin (A1AT) is a protein that is produced in the liver and released into the bloodstream. A1AT works by inactivating several enzymes but the main one is the enzyme elastase present in the lungs. Elastase is an enzyme produced by neutrophils (a type of white blood cell) and it is part of the body’s normal response to injury and inflammation. Elastase breaks down proteins so that they can be removed and used again by the body but, if its action is not regulated by A1AT, elastase will also begin to break down and damage lung tissue.

A1AT is the product of the protease inhibitor (SERPINA1) gene, of which everyone has two copies. Each SERPINA1 gene copy is responsible for producing half of the body's A1AT. If there is a change (called a mutation) in one or both of the gene copies, then either less A1AT is produced or that which is produced does not work properly. If the A1AT production drops down to less than 30%, then the affected patient will experience a disease called alpha-1-antitrypsin deficiency. Patients with this disorder are at a considerable risk of developing emphysema (a long term lung disease which gradually gets worse) when they are young adults. If they smoke, or are exposed to dust or fumes at work, the lung damage can occur sooner and be more severe.

If the A1AT produced does not work properly it can accumulate in the liver cells that produce it. As it builds up in these cells, the A1AT forms abnormal protein chains which begin to destroy the cells and damage the liver. About 10% of those affected with A1AT deficiency will have liver disease as a newborn. Many with the disorder, improve on their own but in severe cases these infants may need a liver transplant to survive. A1AT deficiency is the most common genetic cause of liver disease in babies and children.The amount and function of the A1AT produced depends on the inherited mutation. While there are more than 70 different variations (alleles) in the SERPINA1 gene, only a few are common. Most people in the UK, about 90%, have two copies of the normal M gene (MM). The most common of the abnormal forms are S and Z. Those people with:

• One copy of M and one of S or Z (MS or MZ) will produce reduced amounts of A1AT but should have enough to protect themselves. They will be carriers of the condition, however, and can pass it on to their children.
• Two copies of S (SS) may have no symptoms or be moderately affected (they produce about 60% of the required A1AT).
• One copy of S and one of Z (SZ) are at an increased risk of developing emphysema (they produce only about 40% of normal A1AT)
• Two copies of Z (ZZ) are the most severely affected (they only produce about 10% of the required A1AT) along with those who have one or two copies of rare forms of the SERPINA1 gene which are 'null' (they do not produce any A1AT)

Types of A1AT tests
Different A1AT tests can be used to measure the amount of A1AT, determine which types and concentrations of A1AT protein are present, and determine which SERPINA1 gene alleles a patient has.

• Alpha-1 Antitrypsin, this test measures the amount of A1AT present.
• Alpha-1 Antitrypsin Phenotype, separates out the different types of A1AT proteins produced and compares them to known patterns. It also allows an estimation of the amount of each type present. A protein electrophoresis test is sometimes used to look for a severe A1AT deficiency.
• Alpha-1 Antitrypsin DNA testing, genetic testing that can be done to identify which protease inhibitor gene mutations (SERPINA1 gene alleles) are present. Only the most common mutations are usually tested (M, S, Z). This test can be used to help evaluate affected patients and their family members

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.