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Natural Autoantibodies to Fcγ Receptors in Intravenous Immunoglobulins

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Abstract

A considerable progress has been achieved in the comprehension of the cellular and molecular mechanisms that account for the therapeutic benefit of intravenous immunoglobulin (IVIg) in several autoimmune and inflammatory conditions. However, the precise mechanisms responsible for such a wide range of biological activities have not been proven unambiguously. A wide range of specificities have been identified within IVIg including idiotypes of immunoglobulins, T cell receptor, HLA molecules, several cell surface molecules of immunological importance such as CD4, CD5, Fas, BAFF, cytokines and cytokine receptors, chemokine receptors, CD40 among others. Here we identify and characterize the natural autoantibodies of IgG isotype directed against the human Fc receptors. We show that the F(ab′)2 of IVIg recognize the FcγRIII (CD16) and FcγRII (CD32). Interestingly, the immunopurified anti-FcγIII and anti-FcγII antibodies isolated from IVIg bind soluble and membrane-bound FcR and inhibit rosette formation. Altogether, these results along with previous reports provide pointers on the existence of functionally relevant natural autoantibodies towards a wide range of self-motifs that may participate in regulation of the immune response. Their presence in the therapeutic immunoglobulin preparations may explain at least in part, the beneficial effect of IVIg in autoimmune diseases.

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Authors and Affiliations

  1. EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne UPJV, Amiens, France

    Hicham Bouhlal

  2. Service d’Hématologie Clinique et de Thérapie Cellulaire, CHU Sud, Amiens, France

    Hicham Bouhlal

  3. Institut National de la Santé et de la Recherche Medicale Unité 1138, Paris, France

    Denis Martinvalet, Jean-Luc Teillaud, Catherine Fridman, Jagadeesh Bayry, Sébastien Lacroix-Desmazes & Srini V. Kaveri

  4. Centre de Recherche des Cordeliers, Université Pierre et Marie Curie – Paris 6, UMR S 1138, Paris, France

    Jean-Luc Teillaud, Catherine Fridman, Jagadeesh Bayry, Sébastien Lacroix-Desmazes & Srini V. Kaveri

  5. Université Paris Descartes, UMR S 1138, Paris, 75006, France

    Jean-Luc Teillaud, Catherine Fridman, Jagadeesh Bayry, Sébastien Lacroix-Desmazes & Srini V. Kaveri

  6. UN Secretary-General special Envoy on HIV/AIDS in Eastern Europe and Central Asia, Geneva, Switzerland

    Michel D. Kazatchkine

  7. International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France - Indian Council of Medical Research, India), National Institute of Immunohematology, Mumbai, India

    Jagadeesh Bayry, Sébastien Lacroix-Desmazes & Srini V. Kaveri

  8. Inserm U 1138, Centre de Recherche des Cordeliers, Equipe 16 Immunopathology and therapeutc immunointervention, 15, Rue de l’Ecole de Médecine, 75006, Paris, France

    Srini V. Kaveri

Authors
  1. Hicham Bouhlal
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  2. Denis Martinvalet
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  3. Jean-Luc Teillaud
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  4. Catherine Fridman
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  5. Michel D. Kazatchkine
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  6. Jagadeesh Bayry
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  7. Sébastien Lacroix-Desmazes
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  8. Srini V. Kaveri
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Correspondence to Srini V. Kaveri.

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Bouhlal, H., Martinvalet, D., Teillaud, JL. et al. Natural Autoantibodies to Fcγ Receptors in Intravenous Immunoglobulins. J Clin Immunol 34 (Suppl 1), 4–11 (2014). https://doi.org/10.1007/s10875-014-0019-2

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  • DOI: https://doi.org/10.1007/s10875-014-0019-2

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