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Recombinant IgG Fc More Potent Than Native IVIG
NEW YORK (Reuters Health) Apr 18 - A team of molecular biologists has engineered a recombinant immunoglobulin G (IgG) Fc fragment that possesses higher anti-inflammatory activity than standard intravenous immunoglobulin G (IVIG).
"This therapeutic molecule precisely defines the biologically active component of IVIG and helps guide development of an IVIG replacement with improved activity and availability," Dr. Jeffrey V. Ravetch, at Rockefeller University in New York, and his colleagues report in the April 18 issue of Science.
The researchers determined that the anti-inflammatory activity of IgG is mediated by the 2,6 sialylation of the N-linked glycan of the IgG Fc fragment .
Based on that information, they generated IVIG-derived Fc fragments enriched in 2,6 sialic acid and tested the fragments' ability to reduce footpad swelling in a serum-induced murine model of arthritis. The synthetic version had more potent anti-inflammatory activity than standard IVIG, they report.
To confirm that the 2,6-sialylated IgG Fc glycan, and not other components of the IVIG Fc preparations, is responsible for the observed in vivo anti-inflammatory activity, the investigators engineered purified 2,6-silalylated recombinant human IgG1 Fc.
Both preparations - the IVIG-derived sialic-enriched Fc fragments and the in vitro 2,6-sialylated IVIG-derived Fc fragments - "were active at 30 mg/kg, as compared with the 1000 to 2000 mg/kg required for native IVIG."
Dr. Ravetch and his associates conclude that recombinant IgG Fc represents a potential anti-inflammatory drug for treatment of human autoimmune diseases.
Science 2008;320:373-376.
Reuters Health Information 2008. © 2008 Reuters Ltd.
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