ADOLESCENTS WITH ALPHA(1)-ANTITRYPSIN DEFICIENCY HAVE HIGH ALPHA(2)-MACROGLOBULIN AND LOW NEUTROPHIL LIPOCALIN AND ELASTASE LEVELS IN PLASMA

Eighteen-year-old adolescents with alpha(1)-antitrypsin (alpha(1)AT) d eficiency have mostly normal lung function tests. We hypothesized that compensatory increases in other protease inhibitors and/or a decrease d leukocyte activity might favorably affect the protease/protease-inhi bitor balance in alpha(1)AT-deficient adolescents. At the age of 18 y 46 PiZZ (severe deficiency), 22 PiSZ (moderate deficiency), and 41 con trol subjects were studied. The plasma protease inhibitors alpha(2)-ma croglobulin (alpha(2)M), alpha(1)-antichymotrypsin (Achy), and secreto ry leukocyte protease inhibitor (SLPI) were studied, and the protease elastase complexed with alpha(1)AT (HEAT) and neutrophil gelatinase-as sociated lipocalin (NGAL) as indicators of neutrophil leukocyte activi ty. Significantly higher concentrations of alpha(2)M 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 < 0.00 01). Low levels of HEAT were found in PiZZ subjects (p < 0.0005). High er concentrations of Achy were found in PiZZ (p < 0.04) and PiSZ (p < 0.05) individuals. Increased concentrations of alpha(2)M and Achy comb ined with decreased levels of HEAT and NGAL, indicating decreased leuk ocyte activity may, to some extent, compensate for the protease/protea se inhibitor imbalance in the alpha(1)AT-deficiency state.