The history and evolution of immunoglobulin products and their clinical indications

Abstract

The history of providing antibodies to treat diseases began in the 19th century with the discovery of tetanus and diphtheria toxins and the demonstration that immunity to tetanus and diphtheria infections could be transferred by immune sera. Characterization of the mediators of this immunity resulted in the discovery that antibodies are proteins that can be isolated and used to protect against infectious diseases. Development of a method to isolate antibodies from human plasma that could be safely injected into people initiated the development of human gamma globulin preparations to provide antibodies to patients with inherited antibody deficiencies. To overcome the limitations imposed by intramuscular injection of gamma globulin, intravenous gamma globulin preparations were developed that began to be used in a wide variety of clinical conditions. Thus the original clinical indication for infection prevention was expanded to several other indications that employ large doses to suppress inflammatory and autoimmune disorders. The most recent development in immunoglobulin therapy is the production of concentrated immune globulins for subcutaneous injection. Home infusions of subcutaneous immunoglobulin are increasingly used to treat immunodeficient patients and are being studied for other clinical applications.

Secreted IgM: New tricks for an old molecule

“…In a landmark paper published in 1890, Emil von Behring with Shibasaburo Kitasato reported that blood taken from rabbits vaccinated with tetanus bacteria and then injected into mice, protected the mice against lethal doses of Clostridium tetani . Shortly thereafter, Von Behring published similar results using Corynebacterium diphtheria infection of guinea pigs . In 1894, Richard Pfeiffer performed in vitro experiments with Vibrio cholera showing that the plasma of previously immunized guinea pigs could lyse the bacteria, terming this the “Pfeiffer's phenomenon” .…”

“…In 1930, Tiselius developed a technique, later adopted by Landsteiner, to separate and visualize proteins by electrophoresis . Using this technique, Tiselius and Kabat In 1939 identified a major band of serum proteins (γ‐globulins), which we now understand to contain most immunoglobulins …”

“…12 Shortly thereafter, Von Behring published similar results using Corynebacterium diphtheria infection of guinea pigs. [13][14][15] In 1894, Richard Pfeiffer performed in vitro experiments with Vibrio cholera showing that the plasma of previously immunized guinea pigs could lyse the bacteria, terming this the "Pfeiffer's phenomenon". 10 and thus providing a mechanism for the earlier discovered protective capacity of serum.…”

“…which we now understand to contain most immunoglobulins. 9,14,16 The first inference of IgM was made in 1937 in horses immunized with pneumococcus polysaccharide. The vaccine-induced anticarbohydrate antibodies were shown to be 3-4 times larger than -globulins.…”

The wonderful story of monoclonal antibodies

“…Broader preparations of IVIG or intravenous immunoglobulins were developed, still widely used not only for immunodeficient patients but also for the treatment of such autoimmune disorders as immune thrombocytopenic purpura . Nowadays, IVIG are processed in order to try and limit the adverse reactions they may yield …”