Alpha-1-antitrypsin PLowell: a normally functioning variant present in low concentration

Abstract

Background: Alpha-1-antitrypsin deficiency is associated with a high risk for the development of emphysema, particularly for phenotype Pi ZZ, which is both deficient and an abnormal inhibitor of the powerful proteolytic enzyme, human neutrophil elastase. The rare variant PLowell is also expressed at abnormally low levels, but its anti-elastase activity has not been described.

Aim: To study the anti-elastase activity of alpha-1-antitrypsin PLowdl and compare it to the common M, S and Z proteins.

Method: Alpha-1-antitrypsin from a female patient aged 75 years with the rare genotype PLoweU NullBcllingham was studied for its ability to inhibit human neutrophil elastase in a time dependent manner.

Results: PLoweii has near normal function as an inhibitor of human neutrophil elastase with an association rate constant of 7.4 X 106 M'V1 at 25 °C, similar to that of M and S.

Conclusion: Alpha-1-antitrypsin PL is associated with a severe deficiency of alpha-1-antitrypsin similar to Z, but unlike that protein it has near normal function as an anti-elastase.