What is being tested?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 primarily the enzyme elastase 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 recycled 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 (Pi)
gene, of which everyone has two copies. Each Pi 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 less A1AT and/or A1AT that does not work properly is produced. If the resulting A1AT production drops down to 30% of normal or less, then the affected patient will experience a disorder called alpha-1-antitrypsin deficiency. Patients with this disorder are at a considerable risk of developing emphysema (a progressive lung disease) in early adulthood. If they smoke, or are exposed to occupational dust or fumes, the lung damage tends to occur sooner and be more severe.
If the A1AT produced does not work properly it tends to accumulate in the liver cells that produce it. As it builds up in these cells, the A1AT forms abnormal protein chains, and begins to destroy the cells and damage the liver. About 10% of those affected with A1AT deficiency will have liver disease as a newborn. Many improve on their own but in severe cases these infants may require a liver transplant to survive. A1AT deficiency is currently the most common reason for a liver transplant in the paediatric population.
The amount and function of the A1AT created depends on the mutation inherited. While there are more than 70 different variations (alleles) in the Pi 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 Pi 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 Pi gene alleles a patient has.
- Alpha-1 Antitrypsin, this test measures the amount of A1AT present
- Alpha-1 Antitrypsin Phenotype, separates out the different variants of A1AT protein being 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 screen for a severe A1AT deficiency
- Alpha-1 Antitrypsin DNA testing, genetic testing that can be done to identify which protease inhibitor gene mutations (Pi 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
