Sugar linkage could lead to better treatment for autoimmune diseases

“With sequential mass spectrometry, we systematically untangle this bush,” says Reinhold. “We take it down to the trunk then try to put it back together to determine its structure.”

Reinhold and Glycomics Center research scientist David Ashline helped Ravetch pinpoint exactly how sialic acid was linked, which let the researchers engineer a synthetic human antibody that mimicked the linkages in IgG, providing an IVIG with enhanced activity for treatment of autoimmune diseases. In the Science paper, the researchers report that when given to arthritic mice, the engineered IgG was about 30 times more effective than IVIG.

“Now that we know what the exact structure is, we can build on it,” says Reinhold. “Just as once you know what the motor in a car is, you can modify and make it more effective, and in principle, if you know the antigen, you can build the antibody.”

Beyond this work with IgG, the Glycomics Center is demystifying the carbohydrate connections in cancer that contributes to metastatic growth and in avian flu where sialic residues on airway surface tissues serve as doorways for viral entry.

“Carbohydrates are the glue that pulls things together, the cell surface matrix in which cells communicate, and they provide the connections for signal transduction. It’s only been within the last decade that we’ve realized that such structures are critical for all kinds of biological function,” says Reinhold. “Now that we can define precise structures, we can begin to understand their function. This structure-functional relationship will have a huge impact on our health in respect to immune regulation.”

To read the abstract of the article, from the April 18 issue of Science, go to http://www.sciencemag.org/cgi/content/abstract/sci;320/5874/373.