J Clin Immunol (2014) 34 (Suppl 1):S4–S11 DOI 10.1007/s10875-014-0019-2

Natural Autoantibodies to Fcγ Receptors in Intravenous Immunoglobulins Hicham Bouhlal & Denis Martinvalet & Jean-Luc Teillaud & Catherine Fridman & Michel D. Kazatchkine & Jagadeesh Bayry & Sébastien Lacroix-Desmazes & Srini V. Kaveri

Received: 6 March 2014 / Accepted: 19 March 2014 / Published online: 1 April 2014 # Springer Science+Business Media New York 2014

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 membranebound 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.

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

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

H. Bouhlal Service d’Hématologie Clinique et de Thérapie Cellulaire, CHU Sud, Amiens, France D. Martinvalet : J.

Natural autoantibodies to Fcγ receptors in intravenous immunoglobulins.

A considerable progress has been achieved in the comprehension of the cellular and molecular mechanisms that account for the therapeutic benefit of in...
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