Alpha 1-antitrypsin deficiency historical perspective
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
Alpha 1-antitrypsin deficiency (A1AD) is a relatively new disease. It was discovered in 1963 by Swedish researchers investigating the context of developed emphysema.
Historical Perspective
A1AD was discovered in 1963 by Carl-Bertil Laurell (1919–2001), at the University of Lund, Sweden.[1]
Laurell, along with a medical resident, Sten Eriksson, made the discovery after noting the absence of the α1 band on protein electrophoresis in five of 1500 samples; three of the five patient samples were found to have developed emphysema at a young age.
The link with liver disease was made six years later, when Sharp et al described A1AD in the context of liver disease.[2]
Molecular Biology
Laurell and Eriksson first discovered alpha-1 antitrypsin (alpha-1 AT) deficiency at the General Hospital in Malmö, Sweden in 1963. Alpha-1 AT is the protease inhibitor in highest concentration in human plasma, and although it is a good inhibitor of trypsin, its primary physiologic target is neutrophil elastase. Alpha-1 AT belongs to the serpin class of serine protease inhibitors, and is synthesized and secreted primarily by hepatocytes, but also the mononuclear phagocytes. Other examples of the serpin class of protease inhibitors include antithrombin, C1-inhibitor, and the many inhibitors of plasminogen. The serine protease inhibitors have a unique ability to undergo a conformational change. An advantage of this molecular mobility is that it enables the inhibitor to snare its target protease and tightly entrap it, forming a complex that can remain stable for hours. A potential disadvantage, however, is that it makes the serpins more than usually vulnerable for dysfunctional mutations.
References
- ↑ Laurell CB, Eriksson S (1963). "The electrophoretic alpha 1-globulin pattern of serum in alpha 1-antitrypsin deficiency". Scand J Clin Lab Invest. 15: 132&ndash, 140.
- ↑ Sharp H, Bridges R, Krivit W, Freier E (1969). "Cirrhosis associated with alpha-1-antitrypsin deficiency: a previously unrecognized inherited disorder". J Lab Clin Med. 73 (6): 934–9. PMID 4182334.