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Mechanisms of IVIG Efficacy in Chronic Inflammatory Demyelinating Polyneuropathy

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Abstract

Background

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable acquired chronic polyneuropathy. Corticosteroids, plasmapheresis and intravenous immunoglobulins (IVIG) have been shown to be effective in randomized controlled clinical trials and IVIG is widely used as a first-line initial and maintenance treatment for CIDP. Studies in animal models of autoimmune diseases indicated that the inhibitory Fc-gamma receptor FcγRIIB, expressed on myeloid cells and B cells, is required for the anti-inflammatory activity of IVIG.

Summary

We found that untreated patients with CIDP, compared to demographically matched healthy controls, show lower FcγRIIB expression levels on naïve B cells and fail to upregulate or to maintain upregulation of FcγRIIB as B cells progress from the naive to the memory compartment. Furthermore, FcγRIIB protein expression is upregulated on B cells and monocytes following clinically effective IVIG therapy suggesting that impaired expression of the inhibitory FcγR in CIDP can, at least partially, be restored by IVIG treatment. In B cells, FcγRIIB transduces an inhibitory signal upon colligation with the B cell receptor, thereby preventing B cells with low affinity or self-reactive receptors from entering the germinal center and becoming IgG positive plasma cells. Our data suggest that this late B cell differentiation checkpoint is impaired in CIDP. Modulating FcγRIIB function might be a promising approach to efficiently limit antibody-mediated immunopathology in CIDP.

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Authors and Affiliations

  1. Clinical Neuroimmunology Group, Department of Neurology, Philipps-University, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany

    Björn Tackenberg

  2. Institute of Genetics, Department of Biology, University of Erlangen-Nuremberg, Staudtstrasse 5, 91058, Erlangen, Germany

    Falk Nimmerjahn

  3. Institute for Experimental Immunology, Clinical Immunology and Immunotherapy, University Hospital Zurich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland

    Jan D. Lünemann

Authors
  1. Björn Tackenberg
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  2. Falk Nimmerjahn
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  3. Jan D. Lünemann
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Correspondence to Jan D. Lünemann.

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Tackenberg, B., Nimmerjahn, F. & Lünemann, J.D. Mechanisms of IVIG Efficacy in Chronic Inflammatory Demyelinating Polyneuropathy. J Clin Immunol 30 (Suppl 1), 65–69 (2010). https://doi.org/10.1007/s10875-010-9398-1

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