Alpha ₁ Antitrypsin in the Livers of Patients with Emphysema

Abstract

Parenchymal liver cells from emphysema patients with an inherited deficiency of alpha(1)-antitrypsin contain globules of glycoprotein that bind fluorescent antibody to alpha(1)-antitrypsin. The globules can be seen after hematoxylin and eosinstaining or on electron microscopy, but are more readily demonstrated by PAS stain of amylase-treated liver sections. It appears that an inappropriately large amount of alpha(1)-antitrypsin is found in the liver even when there is a deficiency in the serum. Genetic variants of the normal antitrypsin molecule may be unable to leave their site of synthesis in the liver cell because of some molecular aberration.

Alpha-1 Antitrypsin Deficiency – A Genetic Risk Factor for COPD

“…AATD is associated with a substantially increased risk for the development of COPD, often by the third or fourth decade, and is also associated with risks for development of liver disease (Sharp et al 1969;Lieberman, Mittman, and Gordon 1972;Sveger 1976), cutaneous panniculitis (Edmonds, Hodge, and Rietschel 1991), bronchiectasis (King et al 1996), vasculitis (Lewis et al 1985), and Wegener's granulomatosis (Barnett, Sekosan, and Khurshid 1999). AATD is characterised by misfolding of the AAT protein and belongs to a class of genetic diseases underpinned by aberrant protein folding collectively termed conformational disorders (Gooptu and Lomas 2009;Greene et al 2008).…”

Alpha-1-Antitrypsin Allele <i>P</i><i>i</i>^S Fails to Show Segregation Distortion

“…1969;Lieberman et al. 1972;Karitzky et al, 1977] suggests that this allele is under nega tive selection pressure.…”

Prevalence of the serpin peptidase inhibitor (alpha-1-antitrypsin) PI*S and PI*Z alleles in Brazilian children with liver disease

“…Even lower levels of SERPINA1 are produced by the PI*Z allele, this variant resulting from the substitution of a glutamic acid residue for a lysine at position 342 in exon V (Brind et al, 1990) and is the most frequent SERPINA1 deficient variant (Alpha-1 Foundation, 2003). Classical studies demonstrated an association of the PI*Z allele with liver disease (Lieberman et al, 1972). Hepatic involvement in SERPINA1 deficiency due to the PI*Z allele seems to be due to the accumulation of mutant proteins in hepatocytes (Perlmutter, 2003) that have been associated with the clini-cal features of SERPINA1 deficiency in the liver (mainly neonatal cholestasis) that can progress to chronic liver disease and cirrhosis (Sharp et al, 1969;Teckman et al, 1996;Lomas and Parfrey, 2004).…”