Polymers in alpha-1 antitrypsin deficiency (AATD) patients receiving a liver transplantation (LT)

AATD is a hereditary condition that makes patients susceptible to early onset emphysema and liver cirrhosis. Homozygous carriage of the Z allele (PI ZZ) results in severe AATD. Alpha-1 antitrypsin (AAT) is primarily produced by hepatocytes, and to a lesser extent by other cell types. Z-AAT polymerizes and accumulates in hepatocytes. A small proportion of these polymers are secreted into the circulation. There is evidence that polymers act as chemoattractants for neutrophils and may contribute to lung inflammation (Strnad et al. NEJM. 2020;382:1443-1455). The contribution of other cell sources to Z-AAT polymer secretion is incompletely understood. We hypothesized that LT in AATD patients, which typically results in normal levels of circulating AAT, reduces circulating polymers. Previously, in two AATD patients no polymers were present in circulation after LT (Tan et al. Eur Respir J. 2014;43:1501-4). Z-AAT polymers were measured in plasma by Western Blot Analysis using a mouse monoclonal antibody (LG96). Figure 1 shows the plasma polymer levels in five Pi ZZ patients before and after LT. Z-AAT polymers were absent in circulation in four patients after LT; in one patient, the level was reduced to 4 µg/ml. Our results show a marked reduction of plasma Z-AAT polymer levels after LT. This shows that the liver is the main source of Z-AAT polymers. The reduction of this secretion may be beneficial for pulmonary function.