Alpha-1 Antitrypsin Deficiency (AATD)

History of Alpha-1 Antitrypsin Deficiency 

Alpha-1 antitrypsin deficiency (AATD) was first reported in 1963 by Carl-Bertil Laurell and Sten Eriksson, who observed a connection between low plasma serum levels of the protein alpha-1 antitrypsin (AAT) and symptoms of pulmonary emphysema.1 Laurell was a medical doctor at Malmo General Hospital and a researcher who taught clinical chemistry at Lund University, both in Sweden.2 His area of interest was mapping patients with pulmonary diseases using then-modern methods such as electrophoresis.2 When he studied the sera of patients with emphysema, he noted atypical patterns of missing α1-bands in the paper electrophoretic laboratory tests.3

Laurell reached out to another Swedish physician, Sten Eriksson, who also worked at Lund University. Eriksson assisted Laurell in mapping patients and organizing large scale studies in 1962. These studies confirmed the existence of AATD in many of the patients with emphysema. They published their groundbreaking research report, “The Electrophoretic α1-Globulin Pattern of Serum in α1-Antitrypsin Deficiency,” in the Scandinavian Journal of Clinical and Laboratory Investigation in 1963 (republished in the COPD: Journal of Chronic Obstructive Pulmonary Disease in 2013).3 

Increased understanding of the biochemical mechanisms of action and genetic transmission of AATD has significantly progressed over the last several decades. In 1998, the Alpha One International Registry (AIR) was founded in response to the World Health Organization’s recommendation to establish an international registry for AATD. More than 20 countries participate in the AIR research project. Every 2 years, AIR convenes regularly to update the medical and scientific communities on the latest AATD research developments. It is now believed that AATD is one the most common serious hereditary disorders, with a similar frequency of appearance to cystic fibrosis.1

What is Alpha-1 Antitrypsin Deficiency?

Alpha-1 Antitrypsin Deficiency (AATD) is an inherited, genetic condition passed down from both parents to their children. This means the mode of inheritance in genetic terms is autosomal codominant: one abnormal gene from the mother combines with another abnormal gene from the father to result in the child’s inheritance of AATD.4 The inheritance of AATD increases the risk of developing nonalcoholic liver disease at any age, including in infancy, childhood, and young adulthood. As the disease progresses in early adulthood, lung diseases such as emphysema, chronic obstructive pulmonary disease (COPD), and chronic bronchitis begin to manifest. Panniculitis and vasculitis are possible signs of AATD, but these symptoms are much rarer.5,6

Alpha-1 antitrypsin (AAT) is a protein produced by the liver that protects lung tissue from the one of the most destructive protease enzymes in the body, neutrophil elastase. Macrophages and neutrophils secrete neutrophil elastase during an infection or during exposure to inflammatory irritants such as tobacco smoke. Neutrophil elastase indiscriminately destroys pathogens as well as host tissue, which, in the lungs, produces symptoms consistent with acute lung injury.7

In AATD, the alpha-1 antitrypsin protein is abnormally shaped, which inhibits its proper release from the liver into the bloodstream for transport to the lungs. The liver can release scant to no AAT in AATD. The abnormally shaped AAT eventually builds up in the liver, which contributes to the development of liver disease.8 The low level of AAT in the blood contributes to increased likelihood of chronic lung inflammation and disease. Lack of inhibition of the activity of neutrophil elastase allows this protease enzyme to attack even healthy lung tissue in individuals with AATD due to the absence of functional, regulatory AAT.9 This unregulated destruction of the alveolar lung tissue where gas exchange occurs leads to progression of the symptoms of emphysema in individuals as young as 30.9


  1. Stolk J, Seersholm N, Kalsheker N. Alpha1-antitrypsin deficiency: current perspective on research, diagnosis, and management. Int J Chron Obstruct Pulmon Dis. 2006;1(2):151-160. doi:10.2147/copd.2006.1.2.151
  2. AATD Awareness Sweden. Mereo BioPharma. Accessed May 25, 2021.
  3. Laurell, CB, Eriksson, S. The electrophoretic α1-globulin pattern of serum in α1-antitrypsin deficiency. Scandinavian Journal of Clinical and Laboratory Investigation. 1963; 15(2):132-140.. Republished in: COPD: Journal of Chronic Obstructive Pulmonary Disease. 2013;10(S1):3-8. doi:10.3109/15412555.2013.771956
  4. What is alpha-1? Alpha-1 Foundation. Accessed May 25, 2021.
  5. Franciosi AN, Ralph J, O’Farrell NJ, et al. Alpha-1 antitrypsin deficiency-associated panniculitis. J Am Acad Dermatol. 2021;S0190-9622(21)00232-2. doi:10.1016/j.jaad.2021.01.074
  6. Blanco I, Bueno P, Diego I, et al. Alpha-1 antitrypsin Pi*SZ genotype: estimated prevalence and number of SZ subjects worldwide. Int J Chron Obstruct Pulmon Dis. 2017;12:1683-1694. doi:10.2147/COPD.S137852
  7. Kawabata K, Hagio T, Matsuoka S. The role of neutrophil elastase in acute lung injury. Eur J Pharmacol. 2002;451(1):1-10. doi:10.1016/s0014-2999(02)02182-9
  8. Alpha-1 antitrypsin deficiency. Medline Plus. Accessed May 25, 2021.
  9. What is alpha-1? Healthcare providers guide. Alpha-1 Foundation. Accessed May 26, 2021.

Article reviewed by Michael Sapko, MD, on July 1, 2021.