Source: Annual Congress 2012 - COPD treatments: efficacy and safety
Disease area: Airway diseases

Abstract

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.

Rating:

Share or cite this content

Citations should be made in the following way:
I. Ferrarotti, T.P. Carroll, S. Inghilleri, S. Ottaviani, M. Luisetti, N.G. McElvaney (Pavia, Italy; Dublin, Ireland). Effect of augmentation therapy on immune function of patients with severe Alpha1-antitrypsin deficiency. Eur Respir J 2012; 40: Suppl. 56, 2119

Member's Comments

No comment yet.

Related content which might interest you: The effect of augmentation therapy on systemic and pulmonary inflammation markers in α1-antitrypsin deficiency patients Source: Annual Congress 2010 - Recent developments of molecular pathology and functional genomics in non-neoplastic and neoplastic lung diseases Year: 2010 Efficacy of augmentation therapy for emphysema associated with alpha1-antitrypsin deficiency: enough is enough Source: Eur Respir J 2016; 47: 35-38 Year: 2016 Effect of intravenous alpha-1-antitrypsin augmentation therapy on proteinase-3-generated AaVal541 in deficient patients Source: Virtual Congress 2021 – Airway pharmacology: translational and basic science Year: 2021 Prevalence of alpha1-antitrypsin deficiency and its influence on lung function decline in patients with severe asthma Source: Virtual Congress 2020 – Advances in asthma treatment Year: 2020 Long-term effect of alpha-1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients Source: Virtual Congress 2021 – Treatments for airway diseases Year: 2021 Impact of alpha 1-antitrypsin deficiency and prior augmentation therapy on patients' survival after lung transplantation Source: Eur Respir J, 50 (3) 1700962; 10.1183/13993003.00962-2017 Year: 2017 Comparison of outcomes in augmentation naïve and augmented patients with alpha-1 antitrypsin deficiency related lung disease. Source: International Congress 2019 – COPD clinical studies: bronchodilators, corticosteroids and more Year: 2019 Effect of enzyme replacement therapy (ERT) on lung involvement and changes of different peripheral blood T-cell subsets in Fabry disease patients Source: Annual Congress 2013 –Clinical management of orphan lung diseases Year: 2013 Immunoglobulin treatment with recommended dosages do not prevent deterioration in lung function in primary hypogammaglobulinemia Source: Eur Respir J 2006; 28: Suppl. 50, 557s Year: 2006 Effect of 2-Year therapy with Roflumilast in severe systemic inflammation in COPD with metabolic syndrome Source: International Congress 2019 – Advances in COPD pharmacology Year: 2019 Intravenous α1-antitrypsin in a child with deficiency and severe lung disease Source: Eur Respir J 2009; 34: 278-279 Year: 2009 Pulmonary administration of alpha1-antitrypsin for the treatment of Alpha1-antitrypsin deficiency Source: Eur Respir J 2003; 22: Suppl. 45, 385s Year: 2003 Alterations of lung function in children with juvenile idiopathic arthritis under therapy Source: Eur Respir J 2002; 20: Suppl. 38, 139s Year: 2002 Current and future therapy of lung emphysema caused by alpha-1-antitrypsin deficiency Source: Annual Congress 2004 - Alpha-1-antitrypsin deficiency: Current knowledge and new frontiers Year: 2004 Pulmonary and systemic inflammatory response in patients with pulmonary infections receiving long-term glucocorticoid therapy Source: Eur Respir J 2002; 20: Suppl. 38, 15s Year: 2002 Severe asthma in old patients is characterized by signs of immunosuppression and by lymphocyte resistance to glucocorticoids Source: Annual Congress 2012 - Aspects of clinical asthma Year: 2012 The effect of androgen replacement treatment on pulmonary functions in male patients with hypogonadism Source: Eur Respir J 2006; 28: Suppl. 50, 862s Year: 2006 Reversibility of diffusion capacity abnormalities in patients with clinical hypothyroidism with establishment of euthyroid state Source: Annual Congress 2013 –New issues in lung function testing Year: 2013 Influence of N-acetylcystein in complex basic therapy on the dynamics of pulmonary function test indices in severe bronchial asthma patients Source: Annual Congress 2008 - Comorbid cardiovascular condition and therapy of asthma Year: 2008 The withdrawal of replacement therapy and outcomes in alpha-1 antitrypsin deficiency lung transplant recipients Source: Eur Respir J, 53 (5) 1900055; 10.1183/13993003.00055-2019 Year: 2019