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S‐Sulfonation: a Reversible Chemical Modification of Human Immunoglobulins Permitting Intravenous Application
Author(s) -
Hofstaetter T.,
Gronski P.,
Kanzy E.J.,
Schorlemmer H. U.,
Seller F.R.,
AG Behringwerke
Publication year - 1983
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/j.1423-0410.1983.tb01900.x
Subject(s) - complement system , antibody , phagocyte , chemistry , receptor , fragment crystallizable region , immunoglobulin g , effector , immune complex , immunoglobulin fc fragments , immunology , complement receptor , fc receptor , immune system , biochemistry , medicine
. 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 Cγ2 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 imunoglobulins that is reversible, it can be demonstrated that all IgG effector functions important for antigen removal are regained by reconstitution of the disulfide bonds.