title: 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.
authors.affiliation: Department of Paediatrics, University of Lund, University Hospital, Malmö, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Sveger
authors.forename: K
authors.initials: K
authors.lastname: Ohlsson
authors.forename: E
authors.initials: E
authors.lastname: Piitulainen
mesh_terms: D000209:Acute-Phase Proteins; D000293:Adolescent; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood*; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D015513:Oncogene Proteins; D010641:Phenotype; D011518:Proto-Oncogene Proteins; D000514:alpha 1-Antichymotrypsin / Q000097:blood; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D000514:alpha 1-Antichymotrypsin; D000511:alpha-Macroglobulins; D019272:Leukocyte Elastase