ELISA for Specific Detection of PiZ-Related α1-Antitrypsin Deficiency

Abstract

α1-Antitrypsin (AAT) deficiency is a hereditary autosomal disorder resulting from a variety of mutations in the AAT gene. The most common severe deficiency variant of AAT is Z, which has been identified in most populations but occurs most frequently in northwest Europe. The frequency of the Z allele in the US population of European descent is between 0.01 and 0.02, with the homozygous deficiency affecting 1 in every 2000 to 7000 individuals. In Scandinavia, the frequency of the Z allele is considerably higher: at birth, 1 of every 1600 babies is homozygous for the Z allele. Individuals homozygous for the AAT Z allele have a high risk for developing early-onset pulmonary emphysema and/or abnormal liver function in infancy that may lead to complete liver failure. The Z allele is also suspected in patients with Wegener granulomatosis and panniculitis. Here we briefly describe a simple and accurate new ELISA-based test for identifying carriers of the AAT Z allele. AAT is the main circulating and tissue serine protease inhibitor in humans (1). The mean concentration of AAT in serum or plasma in healthy individuals is estimated to be 1.3–1.7 g/L, with a half-life of 3–5 days (2)(3). Circulating AAT increases rapidly to concentrations exceeding 2 g/L in response to a wide range of inflammatory conditions, infections, cancer, liver disease, or pregnancy (4)(5)(6). When the AAT concentration in plasma decreases to <0.7 g/L, the individual is considered AAT-deficient (7). To date, more than 75 alleles have been identified, of which at least 20 affect either the amount or function of the AAT molecule (8). A protein inhibitor (Pi) system has been developed to describe the various allelic variants; this system is based on the migration of the protein in an electric field (9). The position …