TY - JOUR T1 - Effect of augmentation therapy on immune function of patients with severe Alpha1-antitrypsin deficiency JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - P2119 AU - Ilaria Ferrarotti AU - Tomàs P. Carroll AU - Simona Inghilleri AU - Stefania Ottaviani AU - Maurizio Luisetti AU - Noel G. McElvaney Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/P2119.abstract N2 - Alpha-1 antitrypsin (AAT) deficiency is a hereditary disorder caused by mutations in the SERPINA1 gene. Individuals homozygous for the most common mutation Z have markedly reduced AAT concentrations and are predisposed to developing early-onset emphysema. Approximately 5% of AATD individuals have other deficiency alleles including Null alleles which do not express AAT. Although AAT production in monocytes is relatively small in comparison with hepatocytes, local regulation of the antiprotease shield represents an important first line of defence in times of infection and inflammation.Our aim was to investigate the anti-inflammatory properties of AAT by studying individuals homozygous for Null mutations who were receiving augmentation therapy with human plasma derived AAT, and comparing them to ZZ individuals and MM healthy controls.We isolated peripheral blood monocytes from Null/Null and ZZ patients (with/without therapy), and MM controls. To investigate cytokine production, monocytes were maintained for 24 hours in the presence/absence of LPS. ELISAs and quantitative RT-PCRs were used to evaluate cytokine expression. Superoxide production and chemotactic activity were measured in monocytes.Augmentation therapy appeared to attenuate IL-6 and IL-8 production from ZZ monocytes at both. Moreover, we noted a reduced chemotactic activity and superoxide production in AATD individuals receiving augmentation therapy in comparison to untreated AATD patients.Augmentation therapy in AATD individuals (ZZ and Null/Null) appears to modulate immune function and may provide a rationale for reduced exacerbations in subjects receiving augmentation therapy. ER -