title: 7th International Immunoglobulin Conference: Mechanisms of action.
abstract: Although intravenous immunoglobulin (IVIg) 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 (Ig) receptors, including the Fc-gamma receptors (FCγRs) and the neonatal Fc receptor, have revealed genetic variations that are linked to autoimmune diseases and to the efficacy of IVIg treatment. However, the beneficial effect of IVIg encompasses multiple mechanisms of action. One of these is scavenging of activated complement fragments, such as C3a, C5a, C3b and C4b, by infused Ig 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 IgA via specific receptors and/or complement scavenging. Glycosylation of both the Fc- and Fab-fragments has also been implicated in the anti-inflammatory action of IVIg. Although there is evidence to support a role for sialylated IgG glycovariants in mediating the effect of IVIg, evidence from animal models of inflammatory disease suggest that sialylation may not be a critical factor. However, an increase in IgG glycosylation has been observed following IVIg treatment in Guillain-Barré syndrome patients, and this has been associated with improved clinical outcomes.
authors.affiliation: BioVisions, Inc. Headquarters, Potomac, USA.
authors.forename: M
authors.initials: M
authors.lastname: Basta
authors.forename: D R
authors.initials: DR
authors.lastname: Branch
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D003167:Complement Activation / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000628:therapy; D017452:Receptors, IgG / Q000276:immunology; D006023:Glycoproteins
chemical_list: D000893:Anti-Inflammatory Agents; D003165:Complement System Proteins; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; C046179:glycosylated IgG; D006023:Glycoproteins
keywords: autoimmune disease; inflammatory disease; intravenous immunoglobulin; mechanism of action; sialylation