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

  • Sutthi Thampakkul
    Affiliations
    Division of Allergy and Clinical Immunology and Rheumatology, Department of Medicine, Buffalo General Hospital (ST, MB)
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  • Mark Ballow
    Affiliations
    Division of Allergy and Clinical Immunology and Rheumatology, Department of Medicine, Buffalo General Hospital (ST, MB)

    Division of Allergy and Clinical Immunology and Pediatric Rheumatology, Department of Pediatrics, Children's Hospital of Buffalo (MB), State University of New York Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York
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      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.”
      • Wedgwood R.J.
      • Riese G.R.
      Touching a cure of an inveterate phrensy by the transfusion of blood.
      In 1889 von Behring and Kitasato
      • von Behring
      Kitasato Uber das zustandekommen der diptherie-immunitat und der tetanus-immunitat bei thieren.
      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.

      von Pirquet C Frh, Schick B, trans. Die Serumkrankheiten, 1905

      Within a few years, the study of passive immunization was extended to snake venom,
      • Phisalix C.
      • Bertrand G.
      Sur la presence de glandes venimeuses chez les couleuvres et la toxicite du sang de ces animaux: sur la propriete antitoxique du sang des animaux vaccines contre le venin de vipere: reponse a M. Calmette: sur les effets de l'ablation des glandes a venin chez la vipere.
      diphtheria,
      • Ehrlich P.
      Experimentelle untersuchungen uber immunitat: II. Uber abrin.
      and botulinum antitoxin.
      • Eibl M.M.
      • Wedgwood R.J.
      Intravenous immunoglobulin: A review.
      In 1895 von Behring founded an institution for the production of diphtheria antitoxin and conducted further studies of the other uses of passive immunization.
      • Eibl M.M.
      • Wedgwood R.J.
      Intravenous immunoglobulin: A review.
      In 1903 the American Medical Association initiated successful studies on the prophylactic use of tetanus antitoxin after injuries from Fourth of July fireworks.
      • Eibl M.M.
      • Wedgwood R.J.
      Intravenous immunoglobulin: A review.
      In 1907 Cenci
      • Cenci F.
      Alcune esperienze di sieroimmunizzazione e sieroterapia nel morbillo.
      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.
      • McKhann C.F.
      • Chu F.T.
      Use of placental extract in prevention and modification of measles.
      At the beginning of the World War II, Cohn and colleagues
      • Cohn E.J.
      The history of plasma fractionation.
      • Cohn E.J.
      • Luetscher Jr, J.A.
      • Oncley J.L.
      • et al.
      Preparation and properties of serum and plasma proteins. III. Size and charge of proteins separating upon equilibration across membranes with ethanol-water mixtures of controlled pH, ionic strength and temperature.
      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.
      • Stokes Jr, J.
      • Maris E.P.
      • Gellis S.S.
      Chemical, clinical and immunological studies on the products of human plasma fractionation: XI. The use of concentrated normal human serum gamma globulin (human immune serum globulin) in the prophylaxis and treatment of measles.
      • Stokes Jr, J.
      • Neefe J.R.
      The prevention and attentuation of infectious hepatitis by gammaglobulin.
      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.
      • Barandun S.
      • Kistler P.
      • Jeunet F.
      • et al.
      Intravenous administration of human gammaglobulin.
      • Barandun S.
      • Riva G.
      • Spengler G.A.
      Immunologic deficiency diagnosis, forms and current treatment.
      • Janeway C.A.
      The development of clinical uses of immunoglobulins: A review.
      In 1952 when Bruton
      • Bruton O.C.
      Agammaglobulinemia.
      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
      • Barandun S.
      • Kistler P.
      • Jeunet F.
      • et al.
      Intravenous administration of human gammaglobulin.
      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.
      • Romer J.
      • Spath P.J.
      • Skvaril F.
      • et al.
      Characterization of various immunoglobulin preparations for intravenous application. II. Complement activation and binding to staphyloccus protein A.
      In 1981 the first commercial intravenous immunoglobulin was available in the United States.
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