Natural antibodies, intravenous immunoglobulin and their role in autoimmunity, cancer and inflammation

Authors

  • R. Schwartz-Albiez,

    Corresponding author
    1. German Cancer Research Center, D015, Heidelberg, Germany,
      R. Schwartz-Albiez, Department of Translational Immunology D015, German Cancer Research Center, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. E-mail: r.s-albiez@dkfz.de
    Search for more papers by this author
  • R. C. Monteiro,

    1. INSERM U699, Bichat Medical School, Paris, France,
    Search for more papers by this author
  • M. Rodriguez,

    1. Departments of Immunology and Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA,
    Search for more papers by this author
  • C. J. Binder,

    1. Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences,
    2. Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria,
    Search for more papers by this author
  • Y. Shoenfeld

    1. Department of Medicine ‘B’ and Center for Autoimmune Diseases, Chaim Sheba Medical Center Tel-Hashomer, and
    2. Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
    Search for more papers by this author

R. Schwartz-Albiez, Department of Translational Immunology D015, German Cancer Research Center, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. E-mail: r.s-albiez@dkfz.de

Summary

Natural antibodies are produced by B lymphocytes in the absence of external antigen stimulation. With their ability to recognize self, altered self and foreign antigens, they comprise an important first-line defence against invading pathogens, but are also important for tissue homeostasis. By recognizing oligosaccharides expressed on tumour cells and modified cell surface structures accompanying necrosis, natural antibodies have an important anti-tumorigenic function. IVIg contains a wide spectrum of specificities presented in normal plasma including natural antibodies and has been shown to exert inhibitory effects on tumour cells through a subfraction of anti-vascular endothelial growth factor immunoglobulin (Ig)G antibodies with anti-angiogenic properties. IgA antibodies also have potent immunomodulatory properties, being able to both induce and suppress immune responses. IgA-mediated inhibitory function is able to inhibit several inflammatory diseases including asthma and glomerulonephritis. Autoantibodies of the IgM type, on the other hand, have shown promising results in the treatment of multiple sclerosis. These autoantibodies promote remyelination rather than modulating inflammation. Oxidation-specific epitopes, as found in atherosclerotic lesions and on apoptotic cells, comprise one important target of natural antibodies. By recognizing these epitopes, natural antibodies neutralize proinflammatory responses and mediate atheroprotection.

Ancillary