Robert Anthony, Ph.D.

Massachusetts General Hospital, Harvard Medical School, Boston, MA

2015 New Treatments

2015 Turning Lupus on its Head by Using Antibodies to Fight Inflammation

We have discovered a way to chemically modify an antibody called IgG to reduce the damaging inflammation that characterizes lupus. With our Novel Research Grant, we will test the potential of chemically modified-antibodies as a possible treatment for people with lupus.

Summary

The immune system uses inflammation to control infections and cancer. In autoimmune diseases such as lupus, damaging inflammation occurs when antibodies are mistakenly directed against self. Counterintuitively, an antibody called IgG is often used as a treatment called IVIG to suppress inflammation in a variety of diseases, including autoimmune diseases.

With our Novel Research Grant, we will explore if modified IgG works to reduce inflammation in lupus. Next, we hope to optimize these IgG antibodies to enhance their ability to stop inflammation. Our research uses mouse models to study the potential of these antibodies as a therapeutic option for people with lupus.

Scientific Abstract: 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.