title: On the interaction between agalactosyl IgG and Fc gamma receptors.
abstract: One of the serum abnormalities observed in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is the occurrence of IgG that lacks the terminal galactose on asparagine-linked biantennary complex type oligosaccharides [Gal(0)-IgG] located in the CH2 domain. Additionally, IgG without glycosylation is known to be defective in several effector functions due to a reduced ability to bind to its specific receptors (Fc gamma R). It has thus been speculated that, by analogy with unglycosylated IgG, Gal(0)-IgG may also be functionally impaired or exert altered effector mechanisms. If this were true, Gal(0)-IgG could contribute to the phenotype of above-mentioned autoimmune diseases, like impaired immune complex clearance and defective down-regulation of activated B cells. Here, we show by three different methods that the interaction of Gal(0)-IgG and normally glycosylated IgG with the low-affinity Fc gamma RII (CD32) is indistinguishable with respect both to binding and receptor-mediated signalling. These data argue against a prominent role for Fc gamma R-dependent Gal(0)-IgG interactions in the etiology or pathogenesis of autoimmune diseases.
authors.affiliation: Department of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Blood Transfusion Centre, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Groenink
authors.forename: J
authors.initials: J
authors.lastname: Spijker
authors.forename: I E
authors.initials: IE
authors.lastname: van den Herik-Oudijk
authors.forename: L
authors.initials: L
authors.lastname: Boeije
authors.forename: G
authors.initials: G
authors.lastname: Rook
authors.forename: L
authors.initials: L
authors.lastname: Aarden
authors.forename: R
authors.initials: R
authors.lastname: Smeenk
authors.forename: J G
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: M F
authors.initials: MF
authors.lastname: van den Broek
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005697:Galactosides / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D011485:Protein Binding; D017452:Receptors, IgG / Q000737:chemistry*
chemical_list: D005697:Galactosides; D007074:Immunoglobulin G; D007376:Interleukin-2; D017452:Receptors, IgG