alfa1antitrypsiini

Alfa1antitrypsiini, more commonly known as alpha-1-antitrypsin (A1AT), is a serine protease inhibitor (serpin) produced primarily by the liver and released into the bloodstream. It protects tissues, especially in the lungs, by inhibiting neutrophil elastase and other proteases released during inflammation, thereby preventing excessive breakdown of elastin in the alveolar walls.

Genetics and pathophysiology are central to alfa1antitrypsiini. The protein is encoded by the SERPINA1 gene and circulating levels depend on the inherited variants of this gene. The most studied variants are M (normal), Z and S (deficiency alleles). The Z allele causes misfolding and accumulation of A1AT in hepatocytes, leading to markedly reduced serum levels and increased risk of lung disease; the S allele also lowers levels but to a lesser extent. Individuals can carry combinations such as PiZZ, PiSZ, or PiMM, with PiZZ associated with the most severe deficiency. In the lungs, low A1AT levels permit unchecked neutrophil elastase activity, contributing to early-onset emphysema and COPD, even in non-smokers. Liver disease can accompany deficiency due to accumulation of misfolded A1AT in hepatic cells.

Diagnosis of alfa1antitrypsiini deficiency involves measuring serum A1AT levels and determining the genotype or phenotype of SERPINA1, using methods such as phenotyping by isoelectric focusing or DNA testing. Management is supportive; no cure exists. Treatments include augmentation therapy with intravenous pooled A1AT for individuals with severe deficiency and lung disease, along with standard COPD care (smoking cessation, bronchodilators, inhaled steroids, vaccinations, pulmonary rehabilitation). In rare cases, liver transplantation may be considered for severe liver disease.