Role of alpha-1 antitrypsin in human health and disease

Authors

  • F. de Serres,

    Corresponding author
    1. Center for the Evaluation of Risks to Human Reproduction, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
    • Correspondence: Frederick de Serres, PhD, 632 Rock Creek Road, Chapel Hill, NC 27514-6716, USA.

      (fax: 1-919-967-8681; e-mail: deserres@bellsouth.net).

      and

      Ignacio Blanco, MD, Board of Directors of the Alpha1-Antitrypsin Deficiency Spanish Registry, Lung Foundation Breathe, Spanish Society of Pneumology (SEPAR), Provenza, 108 bajo. 08029, Barcelona, Spain.

      (fax: 34-985-652006; e-mail: ignablanco@yahoo.com).

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  • I. Blanco

    Corresponding author
    1. Board of Directors of the Alpha1-Antitrypsin Deficiency Spanish Registry, Lung Foundation Breathe, Spanish Society of Pneumology (SEPAR), Provenza, Barcelona, Spain
    • Correspondence: Frederick de Serres, PhD, 632 Rock Creek Road, Chapel Hill, NC 27514-6716, USA.

      (fax: 1-919-967-8681; e-mail: deserres@bellsouth.net).

      and

      Ignacio Blanco, MD, Board of Directors of the Alpha1-Antitrypsin Deficiency Spanish Registry, Lung Foundation Breathe, Spanish Society of Pneumology (SEPAR), Provenza, 108 bajo. 08029, Barcelona, Spain.

      (fax: 34-985-652006; e-mail: ignablanco@yahoo.com).

    Search for more papers by this author

Abstract

Alpha-1 antitrypsin (AAT) deficiency is an under-recognized hereditary disorder associated with the premature onset of chronic obstructive pulmonary disease, liver cirrhosis in children and adults, and less frequently, relapsing panniculitis, systemic vasculitis and other inflammatory, autoimmune and neoplastic diseases. Severe AAT deficiency mainly affects Caucasian individuals and has its highest prevalence (1 : 2000–1 : 5000 individuals) in Northern, Western and Central Europe. In the USA and Canada, the prevalence is 1: 5000–10 000. Prevalence is five times lower in Latin American countries and is rare or nonexistent in African and Asian individuals. The key to successful diagnosis is by measuring serum AAT, followed by the determination of the phenotype or genotype if low concentrations are found. Case detection allows implementation of genetic counselling and, in selected cases, the application of augmentation therapy. Over the past decade, it has been demonstrated that AAT is a broad-spectrum anti-inflammatory, immunomodulatory, anti-infective and tissue-repair molecule. These new capacities are promoting an increasing number of clinical studies, new pharmacological formulations, new patent applications and the search for alternative sources of AAT (including transgenic and recombinant AAT) to meet the expected demand for treating a large number of diseases, inside and outside the context of AAT deficiency.

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