Alpha₁-antitrypsin (A₁AT) is a glycoprotein synthesized in the liver and is the main component of the alpha₁ globulins. A₁AT serves to counter the effects of several serine proteases, including elastase and trypsin. When A₁AT is deficient, unopposed activity of these enzymes results in emphysema. The age of occurrence of emphysema varies with the type of deficiency, ZZ being most severe, ZS less severe, and SS least severe. It often varies with the personal habits of the individual, especially regarding smoking. Individuals with A₁AT deficiency have PAS-positive diastase-negative granules accumulate in the periportal hepatocytes. Eventually, damage occurs to the liver resulting in cirrhosis. It is especially important to detect A₁AT deficiency early as a replacement therapy is now available which has received favorable review in a recent NIH study. Although the long-term effects of this therapy are still unknown, it does have great potential to decrease the severity of emphysema.

A₁AT is a positive acute phase protein because it rises whenever there is tissue injury, necrosis, inflammation, or infection. Therefore, patients with A₁AT deficiency who suffer from bronchitis, pneumonia, or similar respiratory inflammation may have falsely normal levels during acute illness. After the acute phase of illness has passed, repeat determinations often reveal the “true” or “resting” A₁AT level which is indicative of the heterozygous phenotypic deficiency.

Therefore, use of high-resolution electrophoresis which would detect the slower electrophoretic migration of the Z and S variants is preferred over quantification of A₁AT by nephelometry or turbidimetry as a preliminary test for this deficiency. Further, a high-resolution electrophoretic system will detect heterozygotes which could lead to important family studies of potentially deficient first-degree relatives who may benefit from therapy.

Serum A₁AT may be increased in patients during normal pregnancy, chronic pulmonary diseases, hereditary angioneurotic edema, gastric diseases, liver diseases, pancreatitis, diabetes, carcinomas, renal diseases, and rheumatic diseases, and it may be decreased in patients with severe protein loss or in improper storage of specimen.

More than 95% of subjects who are severely deficient are homozygous for the Z allele (PiZZ). PiZZ subjects who smoke have a shorter life expectancy than do nonsmoking PiZZ persons. Variation in severity of clinical manifestations is recognized; some subjects with deficiency do not have significant impairment, but development of airway disease is partly a function of age.