Introduction

Alpha-1-antitrypsin (AAT) deficiency is a hereditary disorder associated with the onset of disabling emphysema at a relatively early age. The condition was first recognized by the Swedish workers Laurell and Eriksson [1], who observed a severe deficiency of the alpha- 1 -globulin fraction in a number of sera undergoing routine biochemical examination. The main protein in this fraction was already recognized to be a proteinase inhibitor, known as ‘alpha- 1 -antitrypsin’. Laurell and Eriksson therefore coined the term ‘alpha- 1 -antitrypsin deficiency’ to describe the condition.

AAT has a much wider spectrum of antiproteolytic activity than its name implies and its most important action appears to be the inhibition of the powerful elastase found within the polymorphonuclear leukocytes. In the most severe form of the deficiency (subjects homozygous for protease inhibitor (PI) type Z), the serum AAT may be only 10–20% of normal and the pulmonary elastin may then be degraded by the unopposed action of the elastase. Alternative names for the inhibitor have therefore been introduced such as alpha- 1 -protease inhibitor, but the more familiar name AAT will be used here.

The Pi system

Advances in electrophoretic methods indicated that AAT forms a polymorphic system with a large number of possible biochemical variants; these are known collectively as the Pi system, the abbreviation standing for ‘protease inhibitor’. Over 90 different AAT variants have been described using the method of isoelectric focusing in polyacrylamide gels. The nomenclature has thus become extremely complex; briefly, the variants are designated by a capital letter corresponding to their mobility by the isoelectric focusing method with the addition of a name or number if necessary.