Immunogenicity of recombinant human proteins: causes and consequences

J Neurol. 2004 Jun;251 Suppl 2:II4-9. doi: 10.1007/s00415-004-1202-9.


Antibodies develop to varying degrees during treatment with human proteins, including insulin, growth hormone, granulocyte-macrophage colony-stimulating factor, factor VIII, erythropoietin, and interferons. These antibodies may reduce the clinical efficacy of these agents by blocking or neutralizing their biologic activity and may have other biologic effects. For example, antibodies develop in 20 % to 40% of patients with severe hemophilia treated with human factor VIII; the presence of these antibodies can result in tolerance to the clotting effects of this agent. Similarly, a proportion of patients treated with interferon alpha develop antibodies, which inhibit its therapeutic effects. Therefore, it is important to test for neutralizing antibodies during treatment with these agents, particularly in patients who are unresponsive to treatment or have breakthrough disease. This article reviews the incidence and clinical impact of antibodies that develop in response to some of the commonly used protein therapeutic agents.

Publication types

  • Review

MeSH terms

  • Antibodies / immunology*
  • Antibody Formation / physiology*
  • Erythropoietin / immunology
  • Erythropoietin / therapeutic use
  • Factor VIII / immunology
  • Factor VIII / therapeutic use
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Human Growth Hormone / immunology
  • Human Growth Hormone / therapeutic use
  • Humans
  • Insulin / immunology
  • Insulin / therapeutic use
  • Interferon-alpha / immunology
  • Interferon-alpha / therapeutic use
  • Recombinant Proteins / immunology*
  • Recombinant Proteins / therapeutic use


  • Antibodies
  • Insulin
  • Interferon-alpha
  • Recombinant Proteins
  • Erythropoietin
  • Human Growth Hormone
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • F8 protein, human
  • Factor VIII