A single sugar found responsible for an antibody's ability to treat inflammation

For years, researchers have struggled to understand how IVIG worked. It's ability to treat autoimmune diseases seemed to bean apparent contradiction.

Intravenous immunoglobulin (IVIG) is a complex mixture of IgG antibodies made from human plasma that contains the pooled antibodies from thousands of people, and is only FDA-approved to treat a few assorted conditions; nonetheless, practitioners have used it off-label with varied success in patients with lupus, arthritis and asthma, among other autoimmune disorders. In the body, the antibodies in plasma act as part of the immune response to identify and deactivate foreign invaders. When they begin attacking the body's own cells, the same protective immunoglobulins (known as IgG antibodies) can cause autoimmune disorders like lupus, arthritis and asthma. And yet, when IVIG is infused into people with those exact autoimmune conditions, it calms inflammation rather than causes it.

Jeffery Ravetch, Theresa and Eugene M. Lang Professor and head of Rockefeller's Laboratory of Molecular Genetics and Immunology, was struck by this inconsistency. "If IgG triggers autoimmune disease, how could it be pathogenic and therapeutic?" he asked. "We call it the IgG paradox." Six years ago he started an investigation into exactly how IVIG worked, and what he's discovered could one day lead to a whole new class of therapeutics. In a paper published today in the journal Science, Ravetch and his colleagues, Falk Nimmerjahn and Yoshi Kaneko explain what makes IVIG effective: A small fraction of the IgG antibodies in the IVIG solution carry a sugar called sialic acid that is required for its protective ability.

IgG antibodies bind to and activate specific immune cells, with different forms or "subclasses" binding to specific receptors (called Fc receptors) on the immune cell's surface. Antibody subclasses have different abilities to induce inflammation in the body by virtue of their selective ability to engage ei

Contact: Kristine Kelly
Rockefeller University

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