Diagnosis of the hereditary disorder α1-antitrypsin (α1AT) deficiency is critically dependent on quantification of serum levels of α1AT, a 52-kDa antiprotease that serves to protect the lung from destruction by neutrophil elastase. Although the measurement of serum α1AT levels is not difficult, there is no international standard for α1AT, 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 α1AT phenotypes, the present study uses a purified α1AT standard to quantify the α1AT serum levels of 443 individuals with common normal and deficient α1AT 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 α1AT serum levels for each of these phenotypes. Based on these studies, the ranges (5th to 95th percentile) for α1AT serum levels of the common phenotypes are: MM, 20 to 53 μmol/L; SS, 20 to 48 μmol/L; ZZ, 3.4 to 7.0 μmol/L; MZ, 15 to 42 μmol/L; MS, 18 to 52 μmol/L; and SZ, 10 to 23 μmol/L. This α1AT standard and these ranges are being used for the National α1-Antitrypsin Deficiency Registry organized under the auspices of the National Heart, Lung, and Blood Institute.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
- Cardiology and Cardiovascular Medicine