Immunoglobulin G Glycosylation in Diseases

Pezer, Marija

doi:10.1007/978-3-030-76912-3_13

Cited by 3 publications

(4 citation statements)

References 269 publications

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“…Moreover, genome-wide association studies of IgG glycosylation demonstrated the involvement of many transcription factors, receptors, signalling molecules, chromatin remodelers, and other modifiers. In diseases with a pro-inflammatory component such as inflammatory, autoimmune, infectious, cardiometabolic and neoplastic diseases as well as in ageing, the patters of IgG glycosylation in serum show a general trend towards a decreased level of galactosylated and sialylated glycans ( Pezer 2021 ).…”

Section: Glycosylation Of Immunoglobinsmentioning

confidence: 99%

The role of the glycome in symbiotic host-microbe interactions

Aminov,

Aminova

2023

Glycobiology

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Glycosylation plays a crucial role in many aspects of cell biology, including cellular and organismal integrity, structure-and-function of many glycosylated molecules in the cell, signal transduction, development, cancer, and in a number of diseases. Besides, at the inter-organismal level of interaction, a variety of glycosylated molecules are involved in the host-microbiota recognition and initiation of downstream signalling cascades depending on the outcomes of the glycome-mediated ascertainment. The role of glycosylation in host-microbe interactions is better elaborated within the context of virulence and pathogenicity in bacterial infection processes but the symbiotic host-microbe relationships also involve substantive glycome-mediated interactions. The works in the latter field have been reviewed to a much lesser extent, and the main aim of this mini-review is to compensate for this deficiency and summarise the role of glycomics in host-microbe symbiotic interactions.

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Section: Glycosylation Of Immunoglobinsmentioning

confidence: 99%

The role of the glycome in symbiotic host-microbe interactions

Aminov,

Aminova

2023

Glycobiology

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“…Finally, an α-1,6 fucose residue (core fucose) is present in 90% of complex type IgG N-glycans ( Figure 1B ). Interestingly the presence of bisecting GlcNAc inhibits α-1,6 core fucosylation due to steric hindrance and therefore IgGs generally contain either a bisecting GlcNAc or a core fucose residue, although some IgGs may have both bisecting GlcNAc and fucose ( 2 , 27 – 29 ). IgGs are composed of least 30 glycovariants, to which specific abbreviations have been assigned: G0 (no Gal residue), G1 (1 Gal), G2 (2 Gals), F (fucose) etc ( Figure 1B ) ( 2 , 27 – 29 ).…”

Section: The Igg N-linked Glycansmentioning

confidence: 99%

“…v. Another strategy is to engineer CHO clones with higher β-1,4-N-acetylglucoseaminyl-transferase III (GnTIII), best with a Golgi localization domain ( 2 , 31 , 46 , 47 ). GnTIII catalyzes the transfer of GlcNAc to a core mannose residue in N-linked oligosaccharides via a β-1,4 linkage, which results in the formation of a bisected sugar chain.…”

Section: Strategies To Generate Therapeutic Igg1 With Low Levels Of F...mentioning

confidence: 99%

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Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies

2022

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The presence of fucose on IgG1 Asn-297 N-linked glycan is the modification of the human IgG1 Fc structure with the most significant impact on FcɣRIII affinity. It also significantly enhances the efficacy of antibody dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells in vitro, induced by IgG1 therapeutic monoclonal antibodies (mAbs). The effect of afucosylation on ADCC or antibody dependent phagocytosis (ADCP) mediated by macrophages or polymorphonuclear neutrophils (PMN) is less clear. Evidence for enhanced efficacy of afucosylated therapeutic mAbs in vivo has also been reported. This has led to the development of several therapeutic antibodies with low Fc core fucose to treat cancer and inflammatory diseases, seven of which have already been approved for clinical use. More recently, the regulation of IgG Fc core fucosylation has been shown to take place naturally during the B-cell immune response: A decrease in α-1,6 fucose has been observed in polyclonal, antigen-specific IgG1 antibodies which are generated during alloimmunization of pregnant women by fetal erythrocyte or platelet antigens and following infection by some enveloped viruses and parasites. Low IgG1 Fc core fucose on antigen-specific polyclonal IgG1 has been linked to disease severity in several cases, such as SARS-CoV 2 and Dengue virus infection and during alloimmunization, highlighting the in vivo significance of this phenomenon. This review aims to summarize the current knowledge about human IgG1 Fc core fucosylation and its regulation and function in vivo, in the context of both therapeutic antibodies and the natural immune response. The parallels in these two areas are informative about the mechanisms and in vivo effects of Fc core fucosylation, and may allow to further exploit the desired properties of this modification in different clinical contexts.

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Simultaneous Monitoring of Monoclonal Antibody Variants by Strong Cation-Exchange Chromatography Hyphenated to Mass Spectrometry to Assess Quality Attributes of Rituximab-Based Biotherapeutics

Marco

Berger

Esser‐Skala

et al. 2021

IJMS

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Different manufacturing processes and storage conditions of biotherapeutics can lead to a significant variability in drug products arising from chemical and enzymatic post-translational modifications (PTMs), resulting in the co-existence of a plethora of proteoforms with different physicochemical properties. To unravel the heterogeneity of these proteoforms, novel approaches employing strong cation-exchange (SCX) high-performance liquid chromatography (HPLC) hyphenated to mass spectrometry (MS) using a pH gradient of volatile salts have been developed in recent years. Here, we apply an established SCX-HPLC-MS method to characterize and compare two rituximab-based biotherapeutics, the originator MabThera® and its Indian copy product Reditux™. The study assessed molecular differences between the two drug products in terms of C-terminal lysine variants, glycosylation patterns, and other basic and acidic variants. Overall, MabThera® and Reditux™ displayed differences at the molecular level. MabThera® showed a higher degree of galactosylated and sialylated glycoforms, while Reditux™ showed increased levels of oligomannose and afucosylated glycoforms. Moreover, the two drug products showed differences in terms of basic variants such as C-terminal lysine and N-terminal truncation, present in Reditux™ but not in MabThera®. This study demonstrates the capability of this fast SCX-HPLC-MS approach to compare different drug products and simultaneously assess some of their quality attributes.

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Immunoglobulin G Glycosylation in Diseases

Cited by 3 publications

References 269 publications

The role of the glycome in symbiotic host-microbe interactions

The role of the glycome in symbiotic host-microbe interactions

Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies

Simultaneous Monitoring of Monoclonal Antibody Variants by Strong Cation-Exchange Chromatography Hyphenated to Mass Spectrometry to Assess Quality Attributes of Rituximab-Based Biotherapeutics

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