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From Immune Substitution to Immuno-modulation

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Antibody Therapy
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Abstract

Intravenous immunoglobulins (IVIG) are currently used in many fields of medicine for replacement and immunomodulation. This review focusses on the milestones in the history of human immunoglobulins since the initial observation by Ogden C. Bruton who described replacement therapy in a single boy with agammaglobulinemia. Since then, the preparations used for treatment have been markedly improved with respect to tolerability, clinical efficacy, and pathogen safety. Preparations and appropriate pumps for sc administration of IgG have been developed offering an alternative mode of treatment for immunodeficient patients. Appropriate replacement today allows patients with humoral immunodeficiencies to reach adulthood and normal or near-normal quality of life. In 1981, a second fundamental discovery was made. Paul Imbach and coauthors in children with ITP, a well-defined autoimmune disease, showed that IVIG has immunomodulatory potential offering a chance for affected children to receive effective treatment with little or no side effects compared to systemic steroids. This new principle of treatment encouraged many researchers worldwide to exploit the potential of IVIG in many other immunopathological situations too. As an example for an alloimmune disease, rhesus hemolytic disease in newborn babies is discussed. Finally, Kawasaki disease (syndrome) as an example for a disease associated with massive inflammation highlights broadness of IgG’s therapeutic potential.

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References

  • Agarwal S, Agrawal DK. Kawasaki disease: etiopathogenesis and novel treatment strategies. Exp Rev Clin Immunol. 2017;13(3):247–58.

    Article  CAS  Google Scholar 

  • Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG level in primary immunodeficiency disease: the IgG level that protects against recurrent infection. J Allergy Clin Immunol. 2008;122(1):210–2.

    Article  CAS  PubMed  Google Scholar 

  • Bruton OC. Agammaglobulinemia. Pediatrics. 1952;9(6):722–8.

    CAS  PubMed  Google Scholar 

  • Burdach SE, Evers KG, Geursen RG. Treatment of acute idiopathic thrombocytopenic purpura of childhood with intravenous immunoglobulin G: comparative efficacy of 7S and 5S preparations. J Pediatr. 1986;109(5):770–5.

    Article  CAS  PubMed  Google Scholar 

  • Debré M, Bonnet MC, Fridman WH, Carosella E, Philippe N, Reinert P, Vilmer E, Kaplan C, Teillaud JL, Griscelli C. Infusion of Fc gamma fragments for treatment of children with acute immune thrombocytopenic purpura. Lancet. 1993;342(8877):945–9.

    Article  PubMed  Google Scholar 

  • Imbach P, Barandun S, d’Apuzzo V, Baumgartner C, Hirt A, Morell A, Rossi E, Schöni M, Vest M, Wagner HP. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet. 1981;1(8232):1228–31.

    Article  CAS  PubMed  Google Scholar 

  • Imbach P, Lazarus AH, Kühne T. Intravenous immunoglobulins induce potentially synergistic immunomodulations in autoimmune disorders. Vox Sang. 2010;98(3 Pt 2):385–94.

    Article  CAS  PubMed  Google Scholar 

  • Janssen WJ, Mohamed Hoesein F, Van de Ven AA, Maarschalk J, van Royen F, de Jong PA, Sanders EA, van Montfrans JM, Ellerbroek PM. IgG trough levels and progression of pulmonary disease in pediatric and adult CVID patients. J Allergy Clin Immunol. 2017;140(1):304–306.e4.

    Article  Google Scholar 

  • Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125(6):1354–60.

    Article  CAS  PubMed  Google Scholar 

  • Matucci A, Maggi E, Vultaggio A. Mechanisms of action of Ig preparations: immunomodulatory and anti-inflammatory effects. Front Immunol. 2015;5:690.

    Article  PubMed  PubMed Central  Google Scholar 

  • Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE, Glode MP, Mason WH, Reddy V, Sanders SP, et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1986;315(6):341–7.

    Article  CAS  PubMed  Google Scholar 

  • Newburger JW, Takahashi M, Beiser AS, Burns JC, Bastian J, Chung KJ, Colan SD, Duffy CE, Fulton DR, Glode MP, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med. 1991;324(23):1633–9.

    Article  CAS  PubMed  Google Scholar 

  • Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: a meta-analysis of clinical studies. Clin Immunol. 2010;137(1):21–30.

    Article  CAS  PubMed  Google Scholar 

  • Perez EE, Orange JS, Bonilla F, Chinen J, Chinn IK, Dorsey M, El-Gamal Y, Harville TO, Hossny E, Mazer B, Nelson R, Secord E, Jordan SC, Stiehm ER, Vo AA, Ballow M. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1–S46.

    Article  CAS  PubMed  Google Scholar 

  • Rübo J, Wahn V. A trial with high-dose gamma globulin therapy in 3 children with hyperbilirubinemia in rhesus incompatibility. Monatsschr Kinderheilkd. 1990;138(4):216–20.

    PubMed  Google Scholar 

  • Rübo J, Wahn V. High-dose intravenous gammaglobulin in rhesus-haemolytic disease. Lancet. 1991;337(8746):914.

    Article  PubMed  Google Scholar 

  • Rübo J, Albrecht K, Lasch P, Laufkötter E, Leititis J, Marsan D, Niemeyer B, Roesler J, Roll C, Roth B, et al. High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease. J Pediatr. 1992;121(1):93–7.

    Article  PubMed  Google Scholar 

  • Wahn V, Orange JS. Clinical use of immunoglobulins UNI-MED science. 2nd ed. Bremen: UNI-MED Verlag AG; 2013.

    Google Scholar 

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Disclosures

In the last years, the author has received honoraria for scientific lectures from Octapharma, CSL Behring, Biotest, PPTA and the FIND-ID network. He was also paid for his work in an advisory board (Pharming) and data safety monitoring board (Octapharma, Pfizer).

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Correspondence to Volker Wahn .

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Wahn, V. (2018). From Immune Substitution to Immuno-modulation. In: Imbach, P. (eds) Antibody Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-68038-5_2

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  • DOI: https://doi.org/10.1007/978-3-319-68038-5_2

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  • Publisher Name: Springer, Cham

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