An old, fickle therapy for a variety of autoimmune diseases is getting a makeover, thanks to a decade-long investigation by Rockefeller University researchers.
The original treatment, called intravenous immunoglobulin or IVIG, is an amalgam of specific antibodies made from the pooled blood plasma of thousands of healthy donors. Physicians have used it both on-label and off in patients with lupus, arthritis, asthma and other immune disorders, to varying degrees of success. But new research shows that understanding how the therapy works at a molecular level can help researchers create a version in the lab that's many times more potent. Jeffrey Ravetch, Theresa and Eugene M. Lang Professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology, has been interested in IVIG ever since he became aware of its inherent paradox: IgG antibodies, the very class of antibodies that triggers autoimmune diseases, give IVIG its anti-inflammatory properties when pooled from healthy donors. In 2006, Ravetch and his colleagues discovered that this apparent contradiction could be attributed to a single sugar molecule called sialic acid, located at the very tip of some IgG antibodies. When present, the molecule confers anti-inflammatory properties. When absent, the IgG molecules lose their protective abilities and can actually cause inflammation.