alpha-1 Antitrypsin

Synonym

Tubes

Additional information

Info

This assay is performed to estimate the concentration of the protein, alpha₁-antitrypsin (AAT) in the blood
AAT is an a1 globulin glycoprotein primarily synthesized by the liver and released into the bloodstream
AAT is a protease inhibitor that inhibits the action of the naturally occurring proteolytic enzymes (e.g. trypsin, elastase, chymotrypsin, collagenase, leukocytic proteases, plasmin and thrombin) which may be released during inflammatory reactions or with cellular necrosis
AAT also acts as an acute phase reactant
Decreased levels or deficiency of AAT allows elastase to degrade lung parenchyma (pulmonary emphysema) and hepatocyte accumulation of unsecreted AAT causes hepatic disease (cirrhosis, liver cancer)

Clinical

Aids in the diagnosis of hereditary absence or deficiency alpha₁-antitrypsin
Evaluation of high-risk emphysema (COPD) patients or asthma unresponsive to typical medical therapy
Evaluation of unexplained liver disease or elevated liver function tests
To screen family members of previously diagnosed AAT deficiency
As a nonspecific test in evaluation of inflammation, severe infection, and necrosis

All individuals with COPD, incompletely reversible asthma, unexplained bronchiectasis, and unexplained liver disease, should be tested for AAT according to recommendations of The World Health Organization (WHO), American Thoracic Society (ATS) and the European Respiratory Society (ERS)
alpha₁-antitrypsin deficiency is passed on as an autosomal recessive trait. Patients who are homozygous for this condition are at considerable risk of developing panacinar emphysema, COPD, or liver disease in infancy or early adulthood
AAT deficiency may clinically manifest as:

Smoking increases the risk of developing emphysema in AAT deficient persons as the tobacco stimulates the leukocytes in lungs to release protease. Thus, onset of dyspnea is often seen at age 30-40 years in smokers and 10-15 years later in nonsmokers

Additional information

AAT deficiency is one of the commonest lethal genetic diseases among Caucasians, affecting 1 per 3000-5000 individuals. The frequency of the heterozygote is about one in twenty and frequency of the homozygote is about one in 1600
AAT deficiency is currently the most common cause for a liver transplant in the pediatric population
Patients with serum AAT levels <70 mg/dL (<0.70 g/L) are likely to have a homozygous deficiency and are at risk for early lung disease
AAT levels with <125 mg/dL (<1.25 g/L) should be followed by phenotype testing to confirm homozygous or heterozygous deficiencies
Limitations of serum AAT testing include:

Individuals who carry only a single abnormal AAT gene may not present with definitive result
Abnormal AAT genes that produce relatively normal levels of a defective AAT protein may be missed
AAT levels appear normal in heterozygous AAT deficient individuals during concurrent infection, pregnancy, estrogen therapy, steroid therapy, cancer, and postoperative periods
As AAT also acts as an acute-phase reactant protein (elevated in inflammatory process), C-reactive protein is performed simultaneously and if positive, the patient should be retested for AAT in 10 to 14 days

Hemolyzed sample
Smoking and failure to fast for 8 hrs before test (possible false-elevated level)
Rheumatoid factor causes falsely elevated levels of AAT
Drugs such as oral contraceptives and corticosteroids (possible false elevation)

Nl Result

Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

High Result

Conditions associated with elevated levels of alpha₁-antitrypsin include:

Low Result

Conditions associated with decreased levels of alpha₁-antitrypsin include:

References

alpha-1 Foundation®. What is alpha-1? alpha-1 Fast Facts. [Homepage on the internet]©2007. Last accessed on October 3, 2007. Available at URL:http://www.alphaone.org/healthcare/?c=03-ATSERS-Standards-PDFs
ARUP Consultants®. alpha-1-Antitrypsin Deficiency - AAT. [Homepage on the internet]©2007. Last reviewed in September 2007. Last accessed on October 3, 2007. Available at URL: http://www.arupconsult.com/Topics/PulmonaryDz/AAT.html
ARUP Laboratories®. alpha-1-Antitrypsin. [Homepage on the internet]©2007. Last accessed on October 3, 2007. Available at URL: http://www.aruplab.com/guides/ug/tests/0050001.jsp
Campos MA et al. Influenza Vaccination in Subjects With alpha-1 Antitrypsin Deficiency. Chest. 2007 Oct 1; [Epub ahead of print]
eMedicine from WebMD®. alpha 1-Antitrypsin Deficiency. [Homepage on the Internet] ©1996-2007. Last updated on September 21, 2006. Last accessed on October 3, 2007. Available at URL: http://www.emedicine.com/med/topic108.htm
Lab Tests Online®. alpha 1-Antitrypsin Deficiency. [Homepage on the Internet]©2001-2007 Last reviewed on December 22, 2004. Last accessed on October 3, 2007. Available at URL: http://www.labtestsonline.org/understanding/analytes/alpha1_antitrypsin/glance.html
Ranes J. A review of alpha-1 antitrypsin deficiency. Semin Respir Crit Care Med. 2005;26(2):154-166.
Teckman JH. alpha-1-antitrypsin deficiency: diagnosis, pathophysiology, and management. Curr Gastroenterol Rep. 2006;8(1):14-20.