Immunoglobulin G (IgG) antibodies play an important role in the defense against pathogenic microorganisms but are also responsible for tissue destruction and inflammation during autoimmune diseases such as rheumatoid arthritis and SLE. Paradoxically pooled IgG preparations from thousands of donors (IVIg) are also an efficient treatment to suppress several autoimmune diseases and chronic inflammation. Research over the last years has highlighted the role of the sugar domain attached to the IgG Fc-fragment as a molecular switch, which can enhance or block the pro- and anti-inflammatory effector functions of the antibody molecule. Of note, altered IgG glycosylation patterns, containing low levels of terminal galactose and sialic acid residues, have been associated with active autoimmune disease in RA, SLE, and Crohns disease, for example. As sialylated IgG glycovariants have been suggested to be responsible for the anti-inflammatory activity of IVIg, one possible mechanism of IVIg therapy may be to replenish this active anti-inflammatory and immunomodulatory IgG glycovariant, thereby re-establishing immune homeostasis. The aim of this presentation is to summarize our current knowledge about the molecular and cellular mechanisms involved in the pro- and anti- inflammatory activities of IgG and how we can use novel humanized mouse models to translate the findings obtained in inbred mouse models to the human immune system.
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