Sugar linkage could lead to better treatment for autoimmune diseases

UNH Glycomics Center, Rockefeller University scientists identify linkage

DURHAM, N.H. – Researchers at the University of New Hampshire Glycomics Center have helped identify a specific carbohydrate structure that confers anti-inflammatory activity to a glycoprotein antibody that could lead to improved treatment of autoimmune diseases like lupus or rheumatoid arthritis. The study, reported in a recent edition of the journal Science, was led by immunologist Jeffrey Ravetch of Rockefeller University.

The work revolves around immunoglobulin G (IgG), the most abundant antibody in blood plasma. Intravenous immunoglobulin (IVIG) has within it a trace amount of a very active material that is effective in relieving the inflammatory affects of lupus, rheumatoid arthritis, asthma, and other autoimmune disorders. But because of the trace amounts of active material, effective doses of IVIG need to be very high, frequently leading to unwanted side effects.

This study involved rebuilding the human IVIG into a fully active molecule with a slight modification to a carbohydrate residue. These carbohydrate structures are linked to the immunoglobulin and referred to as glycans, and on the tip of this glycan is a specifically linked sialic acid. All the sialic acid on IVIG was converted to the active linkage that confers anti-inflammatory properties.

Understanding and analyzing the exact structure of sialic acid was the contribution of the UNH Glycomics Center, headed by director and research professor Vernon Reinhold. The center has developed tools and protocols using multidimensional mass spectrometry to determine the structure and functional relationships of these carbohydrates. Reinhold notes that while most biopolymers are linear and thus relatively easy to sequence, bush-shaped carbohydrates have proved challenging.