Therapeutic potential of sialylated IgG Fc in SLE

The canonical functions of IgG antibodies are pro-inflammatory. However, IgG antibodies are routinely administered to suppress inflammation. Intravenous immunoglobulin (IVIG) has been used for over thirty years for treatment of autoimmune and inflammatory diseases including SLE, without a known mechanism of action. A single N-linked glycan is present on each IgG heavy chain. There are over 30 distinct variations of the heterogeneous glycan on IgG recovered from healthy individuals. Importantly, this glycan is the precise determinant that regulates the pro- and anti-inflammatory activities of IgG. Approximately 10% of IgG have glycans terminating in sialic acid. These sialylated IgG are anti-inflammatory, and the biologically activity component of high dose IVIG.  This proposal will harness the anti-inflammatory activity of sialylated IgG for treatment of SLE. The ability of sialylated IgG Fc to attenuate SLE-induced inflammation will be determined using well-established models of SLE. Further, the studies proposed here to explore novel methods of manipulating IgG sialylation in vivo. The therapeutic potential of in vivo sialylation will be explored in SLE models, which may prove to be a novel strategy for attenuating autoantibody-induced inflammation in autoimmune diseases, including SLE.