The history and evolution of immunoglobulin products and their clinical indications

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.