Abstract

Introduction HISTORY Immunologists have been aware of the existence of protective humoral substances in the serum of patients after an infectious episode for a long time. Serum harvested from large animals after their immunization with specific pathogens was injected into humans for the prophylaxis and treatment of serious infections. The concept of immunoglobulin (also called gamma globulin) therapy originated from these early experiments. Subsequently, Paul Ehrlich produced antitoxin to diphtheria in 1897. To avoid complications such as serum sickness with the use of animal serums, attempts were made to concentrate the antibody-containing fractions of human serum. In 1936, placental immunoglobulin samples were used for prophylaxis of measles. In 1952, Bruton recognized that an 8-year-old child who had serious recurrent infections despite conventional therapy was incapable of making significant quantities of immunoglobulin. This was the first time primary immunodeficiency was diagnosed and treated successfully with intramuscular immunoglobulin. Since then, and until 1981, intramuscular gamma globulin or, alternatively, fresh frozen plasma has been the mainstay of treatment of hypogammaglobulinemia and other primary immune deficiencies. In 1981, intravenous immunoglobulin (IVIG) became available commercially in the United States. The advantages of IVIG over intramuscular gamma globulin are: 1) administration is relatively painless; 2) higher doses can be given, resulting in rapid achievement of therapeutic levels, because volume is not a limitation: 3) its absorption is good: 4) it does not undergo local degradation during infusion; and 5) it does not aggregate and activate complement.

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