S-sulfonation: a reversible chemical modification of human immunoglobulins permitting intravenous application. II. Effect on Fc-mediated effector functions.
The generation and release of mediators of inflammation and anaphylaxis via activation of complement or of Fc receptor-bearing cells is held responsible for adverse reactions observed upon intravenous administration of standard immunoglobulins. They are caused by immunoglobulin G (IgG) effector functions predominantly located in the Fc region of the molecule and 'activated' by aggregate formation. Their functional activity depends on the correct conformation of the C gamma 2 domains of Fc and are therefore impaired or even abrogated by S-sulfonation of the hinge disulfide bonds, as demonstrated in this communication: S-sulfonated IgG (S-IgG) has no anticomplementary activity and does not interact with Fc-receptors anymore. After antigen binding, i.e. immune complex (IC) formation, sulfonated IgG is about half as potent as standard IgG in complement activation or phagocyte stimulation (human monocytes and granulocytes). The two activities synergize, however, so that in the presence of complement S-IgG IC are as effective phagocyte activators as standard IC. Moreover, S-sulfonation being the only chemical modification of immunoglobulins that is reversible, it can be demonstrated that all IgG effector functions important for antigen removal are regained by reconstitution of the disulfide bonds.
D000936:Antigen-Antibody Complex / Q000378:metabolism; D001667:Binding, Competitive; D001770:Blood Bactericidal Activity; D003169:Complement Inactivator Proteins / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000502:physiology*; D008163:Luminescent Measurements; D008247:Lysosomes / Q000201:enzymology; D009580:Nitroblue Tetrazolium; D010586:Phagocytes / Q000378:metabolism; D010587:Phagocytosis; D010873:Pinocytosis; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG; D012397:Rosette Formation; D013205:Staphylococcal Protein A / Q000378:metabolism
D000936:Antigen-Antibody Complex; D003169:Complement Inactivator Proteins; C021306:IgG, sulfonated; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D013205:Staphylococcal Protein A; D009580:Nitroblue Tetrazolium