USE OF A HIGHLY PURIFIED ALPHA-1-ANTITRYPSIN STANDARD TO ESTABLISH RANGES FOR THE COMMON NORMAL AND DEFICIENT ALPHA-1-ANTITRYPSIN PHENOTYPES

Diagnosis of the hereditary disorder alpha-1-antitrypsin (alpha-1AT) deficiency is critically dependent on quantification of serum levels of alpha-1AT, a 52-kDa antiprotease that serves to protect the lung from destruction by neutrophil elastase. Although the measurement of serum alpha-1AT levels is not difficult, there is no international standard for alpha-1AT, and investigators in the field recognize that widely used commercially available standards vary by as much as 50 percent. To establish accurate ranges for the common normal and deficient alpha-1AT phenotypes, the present study uses a purified alpha-1AT standard to quantify the alpha-1AT serum levels of 443 individuals with common normal and deficient alpha-1AT phenotypes, including MM, ZZ, SS, MZ, MS, and SZ. Based on the observed values, a statistical model was developed to generate predicted frequency distributions of alpha-1AT serum levels for each of these phenotypes. Based on these studies, the ranges (5th to 95th percentile) for alpha-1AT serum levels of the common phenotypes are: MM, 20 to 53-mu-mol/L; SS, 20 to 48-mu-mol/L; ZZ, 3.4 to 7.0-mu-mol/L; MZ, 15 to 42-mu-mol/L; MS, 18 to 52-mu-mol/L; and SZ, 10 to 23-mu-mol/L. This alpha-1AT standard and these ranges are being used for the National alpha-1-Antitrypsin Deficiency Registry organized under the auspices of the National Heart, Lung, and Blood Institute.