IgG Fc N-glycosylation: Alterations in neurologic diseases and potential therapeutic target?

Kronimus, Yannick; Dodel, Richard; Galuska, Sebastian P.; Neumann, Sascha

doi:10.1016/j.jaut.2018.10.006

Cited by 38 publications

(29 citation statements)

References 162 publications

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“…In these structures, the composition of the carbohydrate dictates the separation distance between the CH2s. The composition of the carbohydrate of the Fc can substantially influence the effector functionality of the antibody as well as the pharmacokinetic profile [75]. efforts can consider altering residues associated with the Fc ball and socket that could impact the flexibility of the Fc, potentially altering effector function activity.…”

Section: The Fc Ch2 Carbohydratementioning

confidence: 99%

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Antibody Structure and Function: The Basis for Engineering Therapeutics

et al. 2019

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Antibodies and antibody-derived macromolecules have established themselves as the mainstay in protein-based therapeutic molecules (biologics). Our knowledge of the structure–function relationships of antibodies provides a platform for protein engineering that has been exploited to generate a wide range of biologics for a host of therapeutic indications. In this review, our basic understanding of the antibody structure is described along with how that knowledge has leveraged the engineering of antibody and antibody-related therapeutics having the appropriate antigen affinity, effector function, and biophysical properties. The platforms examined include the development of antibodies, antibody fragments, bispecific antibody, and antibody fusion products, whose efficacy and manufacturability can be improved via humanization, affinity modulation, and stability enhancement. We also review the design and selection of binding arms, and avidity modulation. Different strategies of preparing bispecific and multispecific molecules for an array of therapeutic applications are included.

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Section: The Fc Ch2 Carbohydratementioning

confidence: 99%

Section: The Fc Ch2 Carbohydratementioning

confidence: 99%

Antibody Structure and Function: The Basis for Engineering Therapeutics

et al. 2019

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“…antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antiinflammatory responses. 16,17 In addition to these structure-function relationships, IgG glycosylation profiles have been shown to be associated with the physiological state of an organism. 18,19 For example, changes in IgG glycosylation have been observed for various indications, including autoimmune diseases and cancer, both in humans [20][21][22] and in mouse models 23 of human disease.…”

Section: Introductionmentioning

confidence: 99%

Towards middle-up analysis of polyclonal antibodies: subclass-specificN-glycosylation profiling of murine immunoglobulin G (IgG) by means of HPLC-MS

Bloechl

Regl

Huber

et al. 2020

Preprint

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Advanced analytical strategies including top-down and middle-up HPLC-MS approaches have become powerful alternatives to classical bottom-up analysis for the characterization of therapeutic monoclonal antibodies. Here, we assess feasibility of middle-up analysis of polyclonal IgGs posing additional challenges due to extensive sequence variability. The presented workflow is based on Fc/2 portions as conserved subunits of IgGs and enables global profiling of subclasses and their glycosylation patterns, both of which influence IgG effector functions. To obtain subunits of murine IgGs, we established digestion with the bacterial protease SpeB. The resulting Fc/2 portions characteristic of different subclasses were subsequently analysed by ion-pair reversed-phase HPLC hyphenated to high-resolution mass spectrometry allowing relative quantification of IgG subclasses and their N-glycosylation variants. In order to assess method capabilities in an immunological context, we applied the analytical workflow to polyclonal antibodies obtained from BALB/c mice immunized with the grass pollen allergen Phl p 6. This analysis simultaneously revealed a shift in IgG subclasses and Fc-glycosylation patterns in total and antigen-specific IgGs from different mouse cohorts. Eventually, Fc/2 characterization may reveal other protein modifications including oxidation, amino acid exchanges, and C-terminal lysine as demonstrated for monoclonal IgGs, which may be implemented for quality control of functional antibodies.

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“…In recent years, people have conducted in-depth research on the glycosylation of various proteins, and clearly understand the important role of protein glycosylation in the occurrence and development of various diseases in humans [1][2][3][4][5][6] . People's interest in the research of immunoglobulin G (Ig G) glycosylation has increased dramatically, and many magazines have published a large number of articles on IgG glycosylation.…”

Section: Introductionmentioning

confidence: 99%

“…People's interest in the research of immunoglobulin G (Ig G) glycosylation has increased dramatically, and many magazines have published a large number of articles on IgG glycosylation. Many studies have shown that changes in Ig G glycosylation level and sugar chain structure are often accompanied by the occurrence and development of various chronic disease [6][7][8] ,Because Ig G glycosylation is highly heterogeneous and can be regarded as a disease phenotype, it may be used as a dynamic disease biomarker from the perspective of predictive, preventive and personalized medicine Thing [9][10][11][12][13][14] . With the rapid increase in the number of articles published, it becomes very di cult to identify new developments and new trends in IgG glycosylation research.…”

Section: Introductionmentioning

confidence: 99%

Knowledge Domain and Emerging Trends of IgG Glycosylation: A Bibliometric Study Based on CiteSpace

Lv¹,

Chen²,

Li³

et al. 2020

Preprint

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Background: The purpose of this paper is to evaluate the international scientific output of Igg glycosylation research by a stoichiometric analysis of the related papers published in the field of IGG glycosylation from 2009 to 2020, to explore the hot spot of IGG glycosylation and the evolution path of IGG glycosylation.Methods: Using the Web of Science core database (WoSCC) to collect the articles related to IgG glycosylation from 2009 to 2020 as the research object, using CiteSpace visualization software to analyze the co-occurrence of countries and institutions, core authors, and keywords. Cited authors and literature, Co-citation analysis of journals, obtaining cooperation maps of research countries / institutions and core authors, literature citation and clustering maps, co-occurrence maps of high-frequency subject headings, displaying related clusters, mutual influences between clusters and Keyword timeline view spectrum of the historical span of important keywords in clustering.Results: We searched 482 articles related to IgG glycosylation published in 227 journals, and observed that in the past 10 years, the number of articles published has generally increased year by year; it has been cited 13262 times, with an average of 27.5 citations per article, showing an upward trend year by year. The core team in the field of IGG glycosylation is mainly from University and research institutes in USA, Australia, Netherlands, Croatia, England, Germany, Ireland, Scotland, China and Japan. A total of 2408 authors participated in the writing of literature on Igg glycosylation, Among them, Wuhrer, Manfred、Lauc, Gordan、Irena Trbojevic Akmacic, Wei Wang and other scholars are the representatives of this research field and have important influence. There are 281 keywords under the theme of IgG glycosylation, of which there are 4 keywords with word frequency ≥100, and hot keywords that serve as bridges are pregnancy、complex、glycan、biosimilar、N-linked glycosylation、hilic-uplc、glycation and form 8 clusters. IgG glycosylation, as the "biomarker" of disease diagnosis and its mechanism has been a research hotspot in recent years.Conclusion: The use of CiteSpace software for quantitative analysis of IgG glycosylation related literature can intuitively demonstrate its development history and current research hotspots and trends, and can provide researchers with reference to the topic selection and research direction. Value and meaning.

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IgG Fc N-glycosylation: Alterations in neurologic diseases and potential therapeutic target?

Cited by 38 publications

References 162 publications

Antibody Structure and Function: The Basis for Engineering Therapeutics

Antibody Structure and Function: The Basis for Engineering Therapeutics

Towards middle-up analysis of polyclonal antibodies: subclass-specificN-glycosylation profiling of murine immunoglobulin G (IgG) by means of HPLC-MS

Knowledge Domain and Emerging Trends of IgG Glycosylation: A Bibliometric Study Based on CiteSpace

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