The glycosylation pattern of immunoglobulins (i.e, the saccharide composition and multitude of attached glycostructures) has a strong influence on the biological properties. Glycosylation of IgG has been shown to be essential for binding to all FcyRs by maintaining an open conformation of the two heavy chains. This absolute requirement of IgG glycosylation for FcyR binding accounts of the inability of deglycosylated IgG antibodies to mediate in vivo triggered inflammatory responses, such as ADCC, phagocytosis and the reelase of inflammatory mediators.

The nature and importance of the conserved Asn297 linked carbohydrate in influencing igG effector functions has long been recognized. Variations in composition of the carbohydrate have been shown to affect the affinity of IgG for three class of FcyR, FcyRI (CD64), FcyRII(CD32), and FcyRIII (CD16) that link IgG antibody mediated immune responses with cellular effector functions. Carbohydrate composition also influences the activity of igG in the classical pathway of complement activation, which is initiated by IgG1 binding to C1q and to mannose binding protections, which structurally resembles C1q. (Shields, J. biological Chemistry, 277(30), 2002)

Effects of Deglycosylated IgGs

It is well described that decllycosylated IgGs are almost completely devoid of all Fc mediated immune effector fucntions as a result of drastically reduced binding to FcyRs or to porteins of the ocmplement system (Ferara, PNAS, 2011, 108(31) 12669-12674).

Effects Sialic acid & galactose:

A low level of galactosylation positively affects complement activation. (Friemoser-Grundshober, (US14/352411))

Nimmerjahn (WO2008/057634) disclose that enrichment of alpha 2,6 linkages between sialic acid and galactose improves anti-inflammatory properties of IVIG fc fragments and removal of attenuates anti-inflammatory properties of IVIG Fc fragments. 

Effects Fucosylation:

Effects on ADCC:  (see also engineered antibodies)

One IgG molecule contains two N-linked oligosacharide sites in the Fc region. The engeral structure of N-linked oligosacharide on IgG is complex-type, characterized by a mannosyl-chitobiose core (Man3GlcNAc2-Asn) with or without bisecting GlcNAc/l-fucose (Fuc) and other cahin variants including the presence or absence of Ga1 and sialic acid. In addition, oligosaccharides may contain zero (G(0) one (G1) or two (G2) Gal. Recent studies have shown that engineering the oligosaccharides of IgGs may hield optimized ADCC. (Shinkawa, J. Biological Chemistry, 278(5), (2003)

ADCC is controlled almost solely by the absence of fucose on IgG1 and galactose and bisecting GLcNAc contribute little or notehring to ADCC (Yaman-Ohunuki ((Biotechnology & Bioengineering, 87(5), 2004).

The lack of core fucose results in higher binding affintiy to FcyRIIIa and thereby enhances ADCC. (Friemoser-Grundshober, (US14/352411))

De-fucosylated by glycosylated Herceptin is at least 50 fold more active in the efficacy of Fcy receptor IIIa mediated ADCC than those with alpha-1,6-linked fucose residues. (Wong, US2011/0263828) teaches the Fc region of an antibody that is specifially glycosylated with oligosaccharides that increase the efficacy and stability of teh Fc region. In one embodiment, the terminal sugar units are sialic acids linked to galactose. 

Lee13 cells, a variant Chinese hamster ovary cell line can be used to produce human IgG1 that are deficient in fucose attached to the Asn297 linked carboyyhydrate. Loack of fucose on the igG1 has no effect on binding to human FcyRi, C1q, or the neonatal Fc rectpror. In contrast, binding of the fucose deficient IgG1 to human FcyRIIIA was improved up to 50 fold. (Shields, J. biological Chemistry, 277(30), 2002)

Removal of core fucose selectively and significantly increases binding affintiy to FcyRIII and leads to enhanced cellular immune effecotr functions, such as ADCC. (Ferara, PNAS, 2011, 108(31) 12669-12674)

Sialic acid: 

The removal (or the absence or reduced levels of sialic acid from the Fc oligosaccharides enhances the avidity of recombinantly produced antibodies for their target molecule (Cai, WO2007/005786)

The carbohydrate structures of all naturally produced antibodies at conserved positions in the heavy chain constant regions vary with isotype. Each isotype possesses a distinct array of N-linked oligosaccharide structures, which variably affect protein assembly, secretion or functional activity.