Alpha-1-Antitrypsin
TECHNICAL UPDATE

DESCRIPTION/BACKGROUND INFORMATION:

The serine proteases are a group of closely related proteolytic enzymes which play a key role in coagulation and fibrinolysis and in kinin and complement activation. The activities of these enxymes are controlled at least in part by specific inhibitors known collectively as serine protease inhibitors, or serpins. The serine protease inhibitor found in highest concentration in plasma is alpha-1-antitrypsin, a glycoprotein which accounts for 90% of the total alpha-1-globulin in plasma.

The major function of alpha-1-antitrypsin (A1A) is to inhibit the activity of leukocyte elastase released in the process of phagocytosis by polymorphonuclear leukocytes. Elastase reacts with elastin in the tracheobronchial tree and vascular endothelium. A1A’s relatively small size and diffusion into these tissues is important in the prevention of loss of elastic recoil. Uninhibited elastase in the bronchial tree, because of either excess elastase or a deficiency in A1A, results in the development of emphysema.

CLINICAL APPLICATION:

The anti-elastase activity of A1A is physiologically the most important. A1A forms a complex with the protease, inactivating it and allowing for clearance of the complex. The unopposed elastase activity is thought to cause destruction of the lung. A1A levels are secondarily low in individual with neonatal respiratory distress syndrome, severe pancreatitis, and protein-losing disorders. Decreased A1A levels due to primary, or genetic, deficiency are associated with a very high risk for development of basilar pulmonary emphysema (in contrast to the apical disease present in other forms of emphysema). Individuals with alpha-1-antitrypsin deficiency have at least a 20-fold increased risk of developing emphysema; 80-90% of deficient individuals eventually develop this condition. Onset of disease is usually much earlier than it is for most other forms of emphysema, with changes beginning in the late second to fourth decades of life. The process is increased by air pollution and cigarette smoking.

A1A deficiency also predisposes to liver disease in children. Neonatal hepatitis with cholestatic jaundice appears in approximately 10% of all newborns with the deficiency. A1A deficiency is currently the most common reason for a liver transplant in the pediatric population. In some adults, A1A deficiency is complicated by cirrhosis, liver cancer, rheumatoid arthritis, and pancreatitis.

As an acute-phase reactant, A1A increases in response to inflammation infections, oral contraceptives, pregnancy, stress, thyroid infections, and with some cancers.

This assay should be run when alpha-1-globulin in serum protein electrophoresis is decreased, when two bands are seen in the alpha-1 region, when the alpha-1 region is obscured by alpha-1 lipoprotein and especially on clinical indications. Caution in interpretation is advised if the patient has been transfused within the previous 14 days.

METHODOLOGY:

Nephlometry

TEST NAME & NUMBER:

• 2306 Alpha-1-Antitrypsin

REFERENCES:

1. Jeppsson JO and Franzen B. Typing of genetic variants of alpha-1-antitrypsin by electrofocusing. Clin Chem 1982; 28:219-225
2. Laurell CB, et al. Protease inhibitors in plasma. In The plasma proteins, 2nd ed, Vol 1. FW Putnam, ed. 1975; New York: Academic Press, 229
3. Nowicki ML and Freier EF. Improved method for identifying alpha-1-antitrypsin Pi M subtypes by isoelectric focusing in agarose. Clin Chem 1990; 36:1815-19
4. SilvermanLM and Christenson RH. Amino acids and proteins. In Tiez textbook of clinical chemistry, 2nd ed. 1994; CA Burtis and ER Ashwood, eds. Philadelphia: W.B. Saunders Co., 673-674.