REPLACEMENT INTRAVENOUS IMMUNE SERUM GLOBULIN THERAPY IN PATIENTS WITH ANTIBODY IMMUNE DEFICIENCY

Abstract

The concept of passive immunization began in the 17th century when Lower and King conducted transfusion experiments, described by Pepys as … mending of bad blood by borrowing from a better body. 101 In 1889 von Behring and Kitasato 97 demonstrated that the blood of tetanus immune rabbits could eliminate the toxic property of tetanus poison and that it had a protective effect when transferred to nonimmune rabbits. At the Pasteur Institute in 1889, Roux and Yersin demonstrated that diphtheria antitoxin could provide passive immunization in children. In the same year Marmerek published studies on passive immunization against scarlet fever; however, the efficacy of the scarlet fever antitoxin was controversial for many years. 98 Within a few years, the study of passive immunization was extended to snake venom, 69 diphtheria, 31 and botulinum antitoxin. 34 In 1895 von Behring founded an institution for the production of diphtheria antitoxin and conducted further studies of the other uses of passive immunization. 34 In 1903 the American Medical Association initiated successful studies on the prophylactic use of tetanus antitoxin after injuries from Fourth of July fireworks. 34 In 1907 Cenci 22 used sera from patients recovering from measles in the prevention of this highly contagious disease. Nicolle and Conseil at the Pasteur Institute confirmed the effectiveness of this procedure in 1917. Subsequently, pooled sera from normal subjects was used with better results and less severe reactions. By 1933, human gamma globulin was extracted from placental tissue by using ammonium sulfate precipitation and demonstrated to be effective in prevention of measles. 62 At the beginning of the World War II, Cohn and colleagues 23,24 from Harvard University developed a method to separate plasma proteins into stable fractions. The concept of Cohn's fractionation was lowering ionic strength to 0.14, reducing the pH to 7.2, and lowering the temperature to −3°C in the presence of low concentrations of ethanol. One of these fractions, fraction II, was an antibody rich fraction. This fraction could be administered in small amounts intramuscularly and had a protective effect against measles and hepatitis A. 91,92 Cohn's fraction II could be given intravenously to normal persons but children with severe infections and who were later recognized to have congenital immune deficiencies developed immediate severe anaphylaxis or anaphylactoid reactions. 7,8,45 In 1952 when Bruton 17 described the first case of agammaglobulinemia, replacement of immunoglobulin was shown to be effective in the treatment of these patients. The replacement, however, could be done only intramuscularly; administration intravascularly caused serious side effects. In the early 1960s Barandun and colleagues 7 with the cooperation of the Swiss Red Cross Laboratories developed the methods to adapt the Cohn fraction II immunoglobulin for intravenous use. A number of intravenous preparations were used in Europe in the 1960s and 1970s. 77 In 1981 the first commercial intravenous immunoglobulin was available in the United States.