Open Access7 th International Immunoglobulin Conference: Mechanisms of Action
Author(s) -
Basta M.,
Branch D. R.
Publication year - 2014
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/cei.12523
Subject(s) - immunology , antibody , receptor , immune system , complement system , immunoglobulin g , glycosylation , complement receptor , medicine , neonatal fc receptor , immunoglobulin fc fragments , biology , biochemistry
Summary Although intravenous immunoglobulin ( IVI g) is widely used for replacement therapy in immunodeficiencies and to treat autoimmune and inflammatory diseases, its mechanisms of action are not fully understood. Examination of immunoglobulin ( I g) receptors, including the F c‐gamma receptors ( FC γ R s) and the neonatal F c receptor, have revealed genetic variations that are linked to autoimmune diseases and to the efficacy of IVI g treatment. However, the beneficial effect of IVI g encompasses multiple mechanisms of action. One of these is scavenging of activated complement fragments, such as C 3a, C 5a, C 3b and C 4b, by infused I g molecules. This interaction prevents binding of complement fragments to their receptors on target cells, thus attenuating the immune damage. Additionally, anti‐inflammatory effects may be facilitated by I g A via specific receptors and/or complement scavenging. Glycosylation of both the F c‐ and F ab‐fragments has also been implicated in the anti‐inflammatory action of IVI g. Although there is evidence to support a role for sialylated I g G glycovariants in mediating the effect of IVI g, evidence from animal models of inflammatory disease suggest that sialylation may not be a critical factor. However, an increase in I g G glycosylation has been observed following IVI g treatment in G uillain‐ B arré syndrome patients, and this has been associated with improved clinical outcomes.