Role of sialylation in the anti-inflammatory activity of intravenous immunoglobulin - F(ab′)<sub>2</sub>versus Fc sialylation

Schwab, Inessa; Nimmerjahn, Falk

doi:10.1111/cei.12527

Cited by 42 publications

(29 citation statements)

References 23 publications

(33 reference statements)

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“…A variety of possible mechanisms was suggested (72). Recent studies emphasized the importance of glycosylation in the therapeutic effects of IVIg (73). In certain mouse models (74,75), but not in others (13,(76)(77)(78), the anti-inflammatory activity of IVIg depends mainly on a fraction of sialylated Abs.…”

Section: Immune Modulation By Fab Glycansmentioning

confidence: 99%

“…Silencing of human B cells via apoptosis could be induced by SNA-enriched IVIg through binding to CD22 (80,85). Altogether, the available literature suggests that the anti-inflammatory effects of IVIg are mediated, at least in part, by its Fab arms, with a potential role for Ig variable domain sialylation (73). Differential effects by SNA-enriched and -depleted fractions might reflect, in part, differences in their respective Ab specificities and not be a direct result of the presence or absence of a glycan (13).…”

Section: Immune Modulation By Fab Glycansmentioning

confidence: 99%

See 1 more Smart Citation

The Emerging Importance of IgG Fab Glycosylation in Immunity

Bovenkamp

Hafkenscheid

Rispens

et al. 2016

The Journal of Immunology

247

216

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Human IgG is the most abundant glycoprotein in serum and is crucial for protective immunity. In addition to conserved IgG Fc glycans, ∼15–25% of serum IgG contains glycans within the variable domains. These so-called “Fab glycans” are primarily highly processed complex-type biantennary N-glycans linked to N-glycosylation sites that emerge during somatic hypermutation. Specific patterns of Fab glycosylation are concurrent with physiological and pathological conditions, such as pregnancy and rheumatoid arthritis. With respect to function, Fab glycosylation can significantly affect stability, half-life, and binding characteristics of Abs and BCRs. Moreover, Fab glycans are associated with the anti-inflammatory activity of IVIgs. Consequently, IgG Fab glycosylation appears to be an important, yet poorly understood, process that modulates immunity.

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Section: Immune Modulation By Fab Glycansmentioning

confidence: 99%

Section: Immune Modulation By Fab Glycansmentioning

confidence: 99%

The Emerging Importance of IgG Fab Glycosylation in Immunity

Bovenkamp

Hafkenscheid

Rispens

et al. 2016

The Journal of Immunology

247

216

View full text Add to dashboard Cite

show abstract

“…[33,51] Most importantly Fab glycosylation can have antiinflammatory effects in vitro and in vivo. [52,53] …”

Section: N-glycosylationmentioning

confidence: 99%

Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

Beyer

Schuster

Jungbauer

et al. 2017

Biotechnology Journal

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Antibodies are typical examples of biopharmaceuticals which are composed of numerous, almost infinite numbers of potential molecular entities called variants or isoforms, which constitute the microheterogeneity of these molecules. These variants are generated during biosynthesis by so‐called posttranslational modification, during purification or upon storage. The variants differ in biological properties such as pharmacodynamic properties, for example, Antibody Dependent Cellular Cytotoxicity, complement activation, and pharmacokinetic properties, for example, serum half‐life and safety. Recent progress in analytical technologies such as various modes of liquid chromatography and mass spectrometry has helped to elucidate the structure of a lot of these variants and their biological properties. In this review the most important modifications (glycosylation, terminal modifications, amino acid side chain modifications, glycation, disulfide bond variants and aggregation) are reviewed and an attempt is made to give an overview on the biological properties, for which the reports are often contradictory. Even though there is a deep understanding of cellular and molecular mechanism of antibody modification and their consequences, the clinical proof of the effects observed in vitro and in vivo is still not fully rendered. For some modifications such as core‐fucosylation of the N‐glycan and aggregation the effects are clear and should be monitored, but with others such as C‐terminal lysine clipping the reports are contradictory. As a consequence it seems too early to tell if any modification can be safely ignored.

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“…63 The role of the sialylation of the F(ab 0 ) 2 part in the function of IVIG therapy is controversial. 64 In one study, high F(ab 0 ) 2 sialylation resulted in a reduction of the anti-inflammatory activity in a murine model of idiopathic thrombocytopenic purpura. 65 In another study, it promoted the production of prostaglandin E2 by monocytes, which in turn suppressed TLR-mediated IFN-a secretion by pDC.…”

Section: Immunoglobulin Fab Fragment Glycosylationmentioning

confidence: 99%

Sweet but dangerous – the role of immunoglobulin G glycosylation in autoimmunity and inflammation

Biermann

Griffante

Podolska

et al. 2016

Lupus

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Glycosylation is well-known to modulate the functional capabilities of immunoglobulin G (IgG)-mediated cellular and humoral responses. Indeed, highly sialylated and desialylated IgG is endowed with anti-and pro-inflammatory activities, respectively, whereas fully deglycosylated IgG is a rather lame duck, with no effector function besides toxin neutralization. Recently, several studies revealed the impact of different glycosylation patterns on the Fc part and Fab fragment of IgG in several autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we provide a synoptic update summarizing the most important aspects of antibody glycosylation, and the current progress in this field. We also discuss the therapeutic options generated by the modification of the glycosylation of IgG in a potential treatment for chronic inflammatory diseases. Lupus (2016) 25, 934-942.

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Role of sialylation in the anti-inflammatory activity of intravenous immunoglobulin - F(ab′)₂versus Fc sialylation

Cited by 42 publications

References 23 publications

The Emerging Importance of IgG Fab Glycosylation in Immunity

The Emerging Importance of IgG Fab Glycosylation in Immunity

Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

Sweet but dangerous – the role of immunoglobulin G glycosylation in autoimmunity and inflammation

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Role of sialylation in the anti-inflammatory activity of intravenous immunoglobulin - F(ab′)2versus Fc sialylation

Cited by 42 publications

References 23 publications

The Emerging Importance of IgG Fab Glycosylation in Immunity

The Emerging Importance of IgG Fab Glycosylation in Immunity

Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

Sweet but dangerous – the role of immunoglobulin G glycosylation in autoimmunity and inflammation

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Role of sialylation in the anti-inflammatory activity of intravenous immunoglobulin - F(ab′)₂versus Fc sialylation