TY - JOUR T1 - Circulating polymers in α<sub>1</sub>-antitrypsin deficiency JF - European Respiratory Journal JO - Eur Respir J SP - 1501 LP - 1504 DO - 10.1183/09031936.00111213 VL - 43 IS - 5 AU - Lu Tan AU - Jennifer A. Dickens AU - Dawn L. DeMeo AU - Elena Miranda AU - Juan Perez AU - S. Tamir Rashid AU - James Day AU - Adriana Ordoñez AU - Stefan J. Marciniak AU - Imran Haq AU - Alan F. Barker AU - Edward J. Campbell AU - Edward Eden AU - Noel G. McElvaney AU - Stephen I. Rennard AU - Robert A. Sandhaus AU - James M. Stocks AU - James K. Stoller AU - Charlie Strange AU - Gerard Turino AU - Farshid N. Rouhani AU - Mark Brantly AU - David A. Lomas Y1 - 2014/05/01 UR - http://erj.ersjournals.com/content/43/5/1501.abstract N2 - To the Editor:Most individuals carry two wild-type M alleles of the SERPINA1 gene which encodes α1-antitrypsin. 95% of severe deficiency of α1-antitrypsin is associated with the Z allele (Glu342Lys; denoted PiZZ in the homozygote), and with the retention and polymerisation of α1-antitrypsin within hepatocytes [1]. These polymers are contained within periodic acid–Schiff-positive, diastase-resistant inclusions that are associated with neonatal hepatitis, cirrhosis and hepatocellular carcinoma. The concomitant lack of circulating α1-antitrypsin predisposes the Z α1-antitrypsin homozygote to early-onset emphysema. Polymers of α1-antitrypsin form within the lung as a result of local inflammation and exposure to cigarette smoke [2]. They have also been identified in the skin of an individual with α1-antitrypsin deficiency and panniculitis [3] and in a renal biopsy from an individual with α1-antitrypsin deficiency and vasculitis [4]. It is unknown whether these polymers form locally or are deposited in these tissues from a circulating source, and whether extrahepatic polymers are associated with any disease phenotypes. We have assessed whether polymers of α1-antitrypsin are present within serum, from where they originate, and whether they are associated with clinical features in individuals with PiZZ α1-antitrypsin deficiency. In this investigation we used ELISA with the anti-α1-antitrypsin polymer monoclonal antibody (2C1) [5] to assess the presence of polymers in the plasma of 1) 518 individuals with PiZZ α1-antitrypsin deficiency; 2) an individual with α1-antitrypsin deficiency who underwent liver transplantation; and 3) 293 individuals with a mixture of α1-antitrypsin phenotypes. The specificity of the 2C1 antibody was confirmed by using it to immunoprecipitate polymers from the plasma of individuals with and without a positive signal … ER -