Adolescents with alpha1-antitrypsin deficiency have high alpha2-macroglobulin and low neutrophil lipocalin and elastase levels in plasma.

Abstract

Eighteen-year-old adolescents with alpha1-antitrypsin (alpha1AT) deficiency have mostly normal lung function tests. We hypothesized that compensatory increases in other protease inhibitors and/or a decreased leukocyte activity might favorably affect the protease/protease-inhibitor balance in alpha1AT-deficient adolescents. At the age of 18 y 46 PiZZ (severe deficiency), 22 PiSZ (moderate deficiency), and 41 control subjects were studied. The plasma protease inhibitors alpha2-macroglobulin (alpha2M), alpha1-antichymotrypsin (Achy), and secretory leukocyte protease inhibitor (SLPI) were studied, and the protease elastase complexed with alpha1AT (HEAT) and neutrophil gelatinase-associated lipocalin (NGAL) as indicators of neutrophil leukocyte activity. Significantly higher concentrations of alpha2M were found in PiZ (p < 0.0001) and PiSZ (p < 0.0001) individuals compared with control subjects. The PiZZ and SZ adolescents had low levels of NGAL (p < 0.0001). Low levels of HEAT were found in PiZZ subjects (p < 0.0005). Higher concentrations of Achy were found in PiZZ (p < 0.04) and PiSZ (p < 0.05) individuals. Increased concentrations of alpha2M and Achy combined with decreased levels of HEAT and NGAL, indicating decreased leukocyte activity may, to some extent, compensate for the protease/protease inhibitor imbalance in the alpha1AT-deficiency state.