Mechanisms of IVIG efficacy in chronic inflammatory demyelinating polyneuropathy

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 firstline 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 antiinflammatory 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 Fc?RIIB as B cells progress from the naive to the memory compartment. Furthermore, Fc?RIIB protein expression is upregulated on B cells and monocytes following clinically effective IVIG therapy suggesting that impaired expression of the inhibitory Fc?R in CIDP can, at least partially, be restored by IVIG treatment. In B cells, Fc?RIIB 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 Fc?RIIB function might be a promising approach to efficiently limit antibody-mediated immunopathology in CIDP. © Springer Science+Business Media, LLC 2010.