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.
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REFERENCES
Amman A.J., Ashman R.F., Buckley R.H., Hardie W.R., Krantmann H.J., Nelson J., Ochs H., Stiehm E.R., Tiller T., Wara D.W., and Wedgwood R. Use of intravenous gamma-globulin in antibody immunodeficiency: Results of a multicenter controlled trial Clin. Immunol. Immunopathol 1982 22 1 60 -67
Baker C.J., Melish M.M., Hall R.T., Casto D.T., Vasan U., and Givner L.B. Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates N. Engl. J. Med 1992 327 4 213 -219
Barandun S., Kistler P., Jeunet F., and Isliker H. Intravenous administration of human gamma globulin Vox Sang 1962 7 157 -174
Baxter Healthcare Corporation, Westlake Village, CA. Gammagard Liquid [Immune globulin infusion (Human) 10%], Prescribing information, 2013.
Baxter Healthcare Corporation. HYQVIA [Immune Globulin Infusion (Human) 10% with Recombinant Human Hyaluronidase] Prescribing information, 2014.
Bender S. and Hetherington S. Haemophilus influenzae type b opsonins of intravenous immunoglobulins J. Clin. Immunol 1987 7 6 475 -480
Berger M., Cupps T.R., and Fauci A.S. Immunoglobulin replacement therapy by slow subcutaneous infusion Ann Int Med 1980 93 55 -56
Berger M., Pinciaro P.J., Althaus A., Ballow M., Chouksey A., Moy J., Ochs H., and Stein M. Efficacy, pharmacokinetics, safety, and tolerability of Flebogamma® 10% DIF, a high-purity human intravenous immunoglobulin, in primary immunodeficiency J. Clin. Immunol 2010 30 2 321 -329
Bernatowska E., Madalinski K., Janowicz W., Weremowicz R., Gutkowski P., Wolf H.M., and Eibl M.M. Results of a prospective controlled two-dose crossover study with intravenous immunoglobulin and comparison (retrospective) with plasma treatment Clin. Immunol. Immunopathol 1987 43 2 153 -162
Biotest Pharmaceuticals Corporation. BIVIGAM [Immune Globulin Intravenous (Human), 10% Liquid, Prescribing Information, 2012. Biotest, Boca Raton, FL.
Bruton O.C. Agammaglobulinemia Pediatrics 1952 9 722 -727
Bussel JB, Kimberly RP, Inman R.D., Schulman I., Cunningham-Rundles C., Cheung N., Smithwick E.M., O’Malley J., Barandun S., and Hilgartner M.W. Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura Blood 1983 62 480 -486
Cohn E.J., Oncley J.L., Strong L.E., Hughes W.L. Jr., and Armstrong S.H. Jr Chemical, clinical, and immunological studies on the products of human plasma fractionation. I. The characterization of the protein fractions of human plasma J. Clin. Invest 1944 23 4 417 -432
Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia N. Engl. J. Med 1988 319 14 902 -907
CSL Behring AG, HIZENTRA [Immune Globulin Subcutaneous (Human) 20% Liquid, Prescribing Information, 2015.
Deener A., Mehra A., Bernstein L., Shliozberg J., and Rubinstein A. Intravenous gammaglobulin treatment in HIV-1 infection Immunol. Allergy. Clin. N. Am 2008 28 4 851 -859
Eijkhout H.W., van Der Meer J.W., Kallenberg C.G., Weening R.S., van Dissel J.T., Sanders L.A., Strengers P.F., Nienhuis H., and Schellekens P.T. Inter-University Working Party for the Study of Immune Deficiencies. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial Ann Intern Med 2001 135 3 165 -74
Encyclopædia Britannica. 2014. Robert Koch. Encyclopædia Britannica Online. Encyclopædia Britannica Inc. <http://www.britannica.com/EBchecked/topic/320834/Robert-Koch>.
Enders J.F. Chemical, clinical, and immunological studies on the products of human plasma fractionation. X. The concentrations of certain antibodies in globulin fractions derived from human blood plasma J. Clin. Invest 1944 23 4 510 -530
Fanaroff A.A., Korones S.B., Wright L.L., Wright E.C., Poland R.L., Bauer C.B., Tyson J.E., Philips J.B., Edwards W., Lucey J.F., Catz C.S., Shankaran S., and Oh W. A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants N. Engl. J. Med 1994 330 16 1107 -1113
FDA Blood Products Advisory Committee Meeting. March 1999. Transcript. http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3504t2.pdf.
FDA Blood Products Advisory Committee Meeting. March 2000. Transcript. http://www.fda.gov/ohrms/dockets/ac/00/transcripts/3603t2a.pdf.
FDA/CBER Guidance for Industry. 2005. Safety, efficacy, and pharmacokinetic studies to support marketing of immune globulin intravenous (human) as replacement therapy for primary humoral immunodeficiency. http://www.fda.gov/cber/guidelines.htm.
FDA/CBER Guidance for Industry. 2008. Safety, efficacy, and pharmacokinetic studies to support marketing of immune globulin intravenous (human) as replacement therapy for primary humoral immunodeficiency. http://www.fda.gov.cber/gdlns/igivimmuno.htm.
Gardulf A., Hammarström L., and Smith C.I.E. Home treatment of hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion Lancet 1991 338 162 -166
Guideline on the clinical investigation of human normal immunoglobulin for intravenous administration (IVIg). 2010. EMA/CHMP/BPWP/94033/2007 rev. 2.
Hagan J.B., Fasano M.B., Spector S., Wasserman R.L., Melamed I., Rojavin M.A., Zenker O., and Orange J.S. Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency J. Clin. Immunol 2010 30 5 734 -745
Hagenbeek A., Brummelhuis G.J., Donkers A., Dumas A.M., Haaft A.T., Schaap B.J.P., Sizoo W., and Lowenberg B. Rapid clearance of cytomegalovirus-specific IgG after repeated intravenous infusions of human immunoglobulin into allogeneic bone marrow transplant recipients J. Infect. Dis 1987 155 5 897 -902
Heidelberger M. and Pedersen K.O. The molecular weight of antibodies J. Exp. Med 1937 65 3 393 -414
Hughes R.A., Donofrio P., Bril V., Dalakas M.C., Deng C., Hanna K., Hartung H.-P., Latov N., Merkies I.S., and Van Doorn P.A. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): A randomised placebo-controlled trial Lancet. Neurol 2008 7 2 136 -144
Imbach P., Barandun S., Baumgartner C., Hirt A., Hofer F., and Wagner H.P. High-dose intravenous gammaglobulin therapy of refractory, in particular idiopathic, thrombocytopenia in childhood Helv. Paediat. Acta 1981 46 81 -86
Immune Globulin Intravenous (IGIV) Indications. 2013. www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm133691.htm.
Jamieson N. and Singh-Grewal D. Kawasaki disease: A clinician’s update Int. J. Pediatrics 2013 2013 1 -7
Janeway C.A., Apt L., and Gitlin D. Agammaglobulinemia Trans. Assoc. Am. Phy 1953 66 200 -202
Janeway C.A., Merler E., Rosen FS, Salmon S., and Crainet J.D. Intravenous gamma globulin. Metabolism of gamma globulin fragments in normal and agammaglobulinemic persons N. Engl. J. Med 1968 278 919 -923
Jolles S., Sein M., Longhurst H.J., Borte M., Ritchie B., Sturzenegger M. H., and Berger M. New frontiers in subcutaneous immunoglobulin treatment Biol. Ther 2011 1 1 1 -15
Kim K.S., Wass C.A., Kang J.H., and Anthony B. Functional activities of various preparations of human intravenous immunoglobulin against type III group B Streptococcus J. Infect. Dis 1986 153 6 1092 -1097
Kitasato S. Über dem Tetanusbacillus Zeitschrift fur Hygience und Infektionskrankheiten 1889 7 225 -234
Lingman-Framme J. and Fasth A. Subcutaneous immunoglobulin for primary and secondary immunodeficiencies: An evidence-based review Drugs 2013 73 12 1307 -1319
McKhann C.F. and Chu F.T. Antibodies in placental extracts J. Infect. Dis 1933 52 2 268 -277
Medical Research Council Hypogammaglobulinemia in the United Kingdom Lancet 1969 1 163 -168
Misbah S., Kuijpers T., van der Heijden Grimbacher B., Guzman D., and Orange J.J. Bringing immunoglobulin knowledge up to date: how should we treat today? Current knowledge in immunoglobulin therapy Clin. Exp. Immunol 2011 166 1 16 -25
Morrison V.A. Infectious complications of chronic lymphocytic leukemia: pathogenesis, spectrum of infection, preventive approaches Best. Pract. Res. Clin. Haematol 2010 23 1 145 -153
Moy J.N., Scharenberg A.M., Stein M.R., Suez D., Roberts R.L., Levy R.J., Ballow M., Fasano M.B., Dash C.H., and Leach S.J. Efficacy and safety of a new immunoglobulin G product, Gammaplex®, in primary immunodeficiency diseases Gammaplex® in PID Clin. Exp. Immunol 2010 162 3 510 -515
NIH Consensus Dev Conf Statement 1990 May 21–23; 8(5). Intravenous immunoglobulin: Prevention and treatment of Disease.
Nolte M.T., Pirofsky B., Gerritz G.A., and Golding B. Intravenous immunoglobulin therapy for antibody deficiency Clin. Exp. Immunol 1979 36 237 -243
Ochs H.D., Gupta S., Kiessling P., Nicolay U., and Berger M. Subcutaneous IgG study group. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases J. Clin. Immunol 2006 26 3 265 -273
Ohlsson A. and Lacy J.B. Intravenous immunoglobulin for preventing infection in preterm and/or low birth weight infants Cochrane Database Systemat. Rev 2013 7 Art. No.: CD000361
Pollack M. Antibody activity against Pseudomonas aeruginosa in immune globulins prepared for intravenous use in humans J. Infect. Dis 1983 147 6 1090 -1098
Raanani P., Gafter-Gvili A., Paul M.M., Ben-Bassat I., Leibovici L., and Shpilberg O. Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis Leukemia Lymphoma 2009 50 5 764 -772
Raanani P., Gafter-Gvili A., Paul M., Ben-Bassat I., Leibovici L., and Shpilberg O. Immunoglobulin prophylaxis in Hematopoietic stem cell transplantation: Systematic review and meta-analysis J. Clin. Oncol 2009 27 5 770 -781
Roifman C.M., Lederman H.M., Lavi S., Stein L.D., Levison H., and Gelfand E.W. Benefit of intravenous IgG replacement in hypogammaglobulinemic patients with chronic sinopulmonary disease Am. J. Med 1985 79 2 171 -174
Roifman C.M., Levison H., and Gelfand E.W. High-dose versus low-dose intravenous immunoglobulin in hypogammaglobulinemia and chronic lung disease Lancet 1987 1 8541 1075 -1077
Schiff R.I. Intravenous gammaglobulin: pharmacology, clinical uses and mechanisms of action Pediatr. Allergy. Immunol 1994 5 2 63 -87
Schroeder D.D., Tankersley D.L., and Lundblad J.L. A new preparation of modified immune serum globulin (human) suitable for intravenous administration I: Standardization of the reduction and alkylation reaction Vox. Sang 1981 40 6 373 -382
Schultze H.E. and Schwick G. Über neue Möglichkeiten intravenöser Gammaglobulin-Applikation Deuthsche. Med. Wchnschr 1962 87 34 1643 -1650
Sgouris J.T. The preparation of plasmin-treated immune serum globulin for intravenous application Vox. Sang 1967 13 71 -84
Sri Kantha S.A. Centennial review; the 1890 tetanus antitoxin paper of von Behring and Kitasato and the related developments Keio. J. Med 1991 40 1 35 -39
Steele R.W. and Steele R.W. Functional capacity of immunoglobulin G preparations and the F(ab′)2 split product J. Clin. Microbiol 1989 27 640 -664
Stein M.R., Nelson R.P., Church J.A., Wasserman R.L., Borte M., Vermylen C., and Bichler J. Safety and efficacy of Privigen®, a Novel 10% liquid immunoglobulin preparation for intravenous use, in patients with primary immunodeficiencies J. Clin. Immunol 2009 29 1 137 -144
Stokes J., Maris E.P., and 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 J. Clin. Invest 1944 23 4 531 -540
Stoll B.J., Gordon T., Korones S.B., Shankaran S., Tyson J.E., Bauer C.R., Fanaroff A.A., Lemons J.A., Donovan E.F., Oh W., Stevenson D.K., Ehrenkranz R.A., Papile L.-A., Verter J., and Wright L.L. Late onset sepsis in very low birth weight neonates: A report from the national institute of child health and human development neonatal research network J. Pediatrics 1996 129 1 63 -71
Tiselius A. Electrophoresis of purified antibody preparations J. Exp. Med 1937 65 5 641 -646
Tiselius A. and Kabat E.A An electrophoretic study of immune sera and purified antibody preparations J. Exp Med 1939 69 1 119 -131
Turner, M. 1989. Molecules which recognize antigen. In Immunology. Edited by IM Roitt, J Brostoff, DK Male. CV Mosby, St. Louis, MO. p 5.8.
Ullmann A. Pasteur-Koch: Distinctive ways of thinking about infectious diseases Microbe 2007 2 8 383 -387
Van der Meché F.G.A., Schmitz P.I.M., and The Dutch Guillain—Barré Study Group A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome New. Eng. J. Med 1992 326 17 1123 -1129
von Behring E. Untersuchungen über das Zustandekommen der Diphtherie-Immunität bei Thieren Deutscbe. Med. Wochenschr 1890 16 50 1145 -1148
von Behring E. and Kitasato S. Über das zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Thieren Dtsch. med Wochenschr 1890 49 1113 -1114
Wasserman R.L., Church J.A., Stein M.R., Moy J., White M., Strausbaugh S., Schroeder H., Ballow M., Harris J., Melamed I., Elkayam D., Lumry W., Suez D., and Rehman S.M. Safety, efficacy, and pharmacokinetics of a new 10% liquid intravenous immunoglobulin (IVIG) in patients with primary immunodeficiency J. Clin. Immunol 2012 32 4 663 -669
Wasserman R.L., Irani A.M., Tracy J., Tsoukas C., Stark D., Levy R., Chen J., Sorrells S., Roberts R., and Gupta S. Pharmacokinetics and safety of subcutaneous immune globulin (human), 10% caprylate/chromatography purified in patients with primary immunodeficiency disease Clin. Exp. Immunol 2010 161 3 518 -526
Wasserman R.L., Melamed I., Kobrynski L., Strausbaugh S.D., Stein M.R., Sharkhawy M., Engl W., Leibl H., Sobolevsky L., Gelmont D., Schiff R.I., and Grossman W.J. Efficacy, safety, and pharmacokinetics of a 10% liquid immune globulin preparation (GAMMAGARD LIQUID, 10%) administered subcutaneously in subjects with primary immunodeficiency disease J. Clin. Immunol 2011 31 3 323 -331
Winston D.J., Ho W.G., Rasmussen L.E., Lin C.-H., Chu C.L., Merigan T.C., and Gale R.P. Use of intravenous immune globulin in patients receiving bone marrow transplants J. Clin. Immunol. 1982 2 April Supplement S2 42S -47S
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LymphoSign Journal
Volume 2 • Number 4 • December 2015
Pages: 181 - 194
History
Received: 29 December 2014
Accepted: 26 February 2015
Accepted manuscript online: 7 April 2015
Version of record online: 7 April 2015
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John A. Hooper. 2015. The history and evolution of immunoglobulin products and their clinical indications. LymphoSign Journal.
2(4): 181-194. https://doi.org/10.14785/lpsn-2014-0025
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