Alpha-1 Antitrypsin Deficiency

The Beginnings

To begin at the beginning . . .

Dylan Thomas 1954

In 1963 the Scandinavian Journal of Clinical and Laboratory Investigation published a paper by Carl-Bertil Laurell and his research student Sten Erikkson.  They had found the first emphysemic patients with what was to become known as alpha-1 antitrypsin deficiency.

. . o o O o o . .

But of course the story did not begin there . . .

The protease inhibitory activity of human plasma was first observed by Fermi and Pernossi in 1894.

Arne Tiselius studied chamistry at Uppsala University. He worked at The Svedberg’s laboratory in 1925 and obtained his doctor’s degree in 1930 on the electrophoresis of proteins. After a spell in Princetonsupported by the Rockefeller Foundation he returned to Uppsala he resumed his interest in proteins, and the application of physical methods to biochemical problems. This led to a much-improved method of electrophoretic analysis which he refined in subsequent years. He received the Nobel Prize for Chemistry in 1948 for discovering how to separate proteins by electrophoresis.

Hermann Schultze of Behring Werke in Marburg, Germany in 1955 showed that the major inhibitor for trypsin is located in the a1-globulin fraction and it was named a1-antitrypsin.

Carl-Bertil Laurell was an early pioneer of plasma protein electrophoresis for clinical investigations.  In 1952 he published an article on paper electrophoresis and in 1961 another article on agarose electrophoresis.

The first case of α1-antitrypsin deficiency.

In late 1950s and the early 1960s the importance of tuberculosis waned and the interest of chest physicians in Sweden turned towards obstructive lung disease and cancer. Samples from patients were sent to Malmö for paper electrophoresis analysis. It was expected that patients with COPD may have some abnormalities in their immunoglobulins. C-B Laurell observed two patient samples with similar paper electrophoretic patterns but both missing the normal α1-band.

This finding was published in 1963: Laurell C-B, Eriksson S. The electrophoretic α1–globulin pattern of serum in a1–antitrypsin deficiency. Scand J clin Lab invest 1963; 15:132-140.

There followed two papers with Erikkson as the first author: Eriksson S, Laurell C-B. A new abnormal serum globulin alpha-1-antitrypsin. Acta Chem Scand 1963; 17: 150-153 Eriksson S. Studies in α1–antitrypsin deficiency. Acta Med Scand 1965, suppl 432:1-85.

Alpha-1 antitrypsin deficiency was now known to the World.