Experientia supplementum (2012)最新文献_第4页

Immunoglobulin G Glycosylation Changes in Aging and Other Inflammatory Conditions. 免疫球蛋白G糖基化在衰老和其他炎症条件下的变化。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_10

Fabio Dall'Olio, Nadia Malagolini

{"title":"Immunoglobulin G Glycosylation Changes in Aging and Other Inflammatory Conditions.","authors":"Fabio Dall'Olio, Nadia Malagolini","doi":"10.1007/978-3-030-76912-3_10","DOIUrl":"https://doi.org/10.1007/978-3-030-76912-3_10","url":null,"abstract":"Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important. The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2. In addition, the structure can present core-linked fucose and/or a bisecting GlcNAc. In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc. These conditions alter also the presence of core-fucose and bisecting GlcNAc. Importantly, similar glycomic alterations are observed in aging. The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging. Glycomic alterations associated with inflammatory diseases often precede disease onset and follow remission. The aberrantly glycosylated IgG glycans associated with inflammation and aging can sustain inflammation through different mechanisms, fueling a vicious loop. These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity. The complex molecular bases of the glycomic changes associated with inflammation and aging are still poorly understood.","PeriodicalId":36906,"journal":{"name":"Experientia supplementum (2012)","volume":"112 ","pages":"303-340"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39549038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Sweet Rules: Linking Glycosylation to Antibody Function. 甜规则:连接糖基化抗体功能。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_12

Falk Nimmerjahn, Anja Werner

{"title":"Sweet Rules: Linking Glycosylation to Antibody Function.","authors":"Falk Nimmerjahn, Anja Werner","doi":"10.1007/978-3-030-76912-3_12","DOIUrl":"https://doi.org/10.1007/978-3-030-76912-3_12","url":null,"abstract":"Antibodies produced upon infections with pathogenic microorganisms are essential for clearing primary infections and for providing the host with long-lasting immunity. Moreover, antibodies have become the most widely used platform for developing novel therapies against cancer and autoimmunity, requiring an in-depth understanding of how antibodies mediate their activity in vivo and which factors modulate pro- or anti-inflammatory antibody activities. Since the discovery that select residues present in the sugar domain attached to the immunoglobulin G (IgG) fragment crystallizable (Fc) region can modulate both, pro- and anti-inflammatory effector functions, a wealth of studies has focused on understanding how IgG glycosylation is regulated and how this knowledge can be used to optimize therapeutic antibody activity. With the introduction of glycoengineered afucosylated antibodies in cancer therapy and the initiation of clinical testing of highly sialylated anti-inflammatory antibodies the proof-of-concept that understanding antibody glycosylation can lead to clinical innovation has been provided. The focus of this review is to summarize recent insights into how antibody glycosylation is regulated in vivo and how select sugar residues impact IgG function.","PeriodicalId":36906,"journal":{"name":"Experientia supplementum (2012)","volume":"112 ","pages":"365-393"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39568549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Glycosylation of Antigen-Specific Antibodies: Perspectives on Immunoglobulin G Glycosylation in Vaccination and Immunotherapy. 抗原特异性抗体的糖基化：免疫球蛋白G糖基化在疫苗接种和免疫治疗中的研究进展。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_18

Pranay Bharadwaj, Margaret E Ackerman

{"title":"Glycosylation of Antigen-Specific Antibodies: Perspectives on Immunoglobulin G Glycosylation in Vaccination and Immunotherapy.","authors":"Pranay Bharadwaj, Margaret E Ackerman","doi":"10.1007/978-3-030-76912-3_18","DOIUrl":"10.1007/978-3-030-76912-3_18","url":null,"abstract":"Exciting developments have been made in understanding antibody-mediated immunity, deepening understanding of antibody effector functions increasingly recognized as critical mechanisms of action beyond antigen recognition, and significantly broadening the evidence base for the importance of these effector mechanisms across diverse infectious and autoimmune diseases. Because these activities critically depend on the specific glycoforms present on a conserved site of the IgG Fc domain, relationships between the Fc glycosylation profiles of antigen-specific antibody pools and outcomes in infectious and autoimmune disease have begun to be defined, pointing to the key role of this posttranslational modification as a biomarker and mechanistic modifier of antibody-mediated immunity. Here we summarize studies evaluating the profiles and activities of antigen-specific antibodies elicited by infection and vaccination as well as within the context of allo- and autoimmunity, and consider current approaches to rational modification of Fc glycans in vivo.","PeriodicalId":36906,"journal":{"name":"Experientia supplementum (2012)","volume":"112 ","pages":"565-587"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39552051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Estrogen-Driven Changes in Immunoglobulin G Fc Glycosylation. 雌激素驱动免疫球蛋白G - Fc糖基化的变化。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_11

Kaitlyn A Lagattuta, Peter A Nigrovic

引用次数: 5

Micro-Heterogeneity of Antibody Molecules. 抗体分子的微观异质性。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_1

Yusuke Mimura, Radka Saldova, Yuka Mimura-Kimura, Pauline M Rudd, Roy Jefferis

{"title":"Micro-Heterogeneity of Antibody Molecules.","authors":"Yusuke Mimura, Radka Saldova, Yuka Mimura-Kimura, Pauline M Rudd, Roy Jefferis","doi":"10.1007/978-3-030-76912-3_1","DOIUrl":"https://doi.org/10.1007/978-3-030-76912-3_1","url":null,"abstract":"Therapeutic monoclonal antibodies (mAbs) are mostly of the IgG class and constitute highly efficacious biopharmaceuticals for a wide range of clinical indications. Full-length IgG mAbs are large proteins that are subject to multiple posttranslational modifications (PTMs) during biosynthesis, purification, or storage, resulting in micro-heterogeneity. The production of recombinant mAbs in nonhuman cell lines may result in loss of structural fidelity and the generation of variants having altered stability, biological activities, and/or immunogenic potential. Additionally, even fully human therapeutic mAbs are of unique specificity, by design, and, consequently, of unique structure; therefore, structural elements may be recognized as non-self by individuals within an outbred human population to provoke an anti-therapeutic/anti-drug antibody (ATA/ADA) response. Consequently, regulatory authorities require that the structure of a potential mAb drug product is comprehensively characterized employing state-of-the-art orthogonal analytical technologies; the PTM profile may define a set of critical quality attributes (CQAs) for the drug product that must be maintained, employing quality by design parameters, throughout the lifetime of the drug. Glycosylation of IgG-Fc, at Asn297 on each heavy chain, is an established CQA since its presence and fine structure can have a profound impact on efficacy and safety. The glycoform profile of serum-derived IgG is highly heterogeneous while mAbs produced in mammalian cells in vitro is less heterogeneous and can be \"orchestrated\" depending on the cell line employed and the culture conditions adopted. Thus, the gross structure and PTM profile of a given mAb, established for the drug substance gaining regulatory approval, have to be maintained for the lifespan of the drug. This review outlines our current understanding of common PTMs detected in mAbs and endogenous IgG and the relationship between a variant's structural attribute and its impact on clinical performance.","PeriodicalId":36906,"journal":{"name":"Experientia supplementum (2012)","volume":"112 ","pages":"1-26"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39549100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Capillary (Gel) Electrophoresis-Based Methods for Immunoglobulin (G) Glycosylation Analysis. 免疫球蛋白(G)糖基化分析的毛细管(凝胶)电泳方法。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_4

Samanta Cajic, René Hennig, Robert Burock, Erdmann Rapp

{"title":"Capillary (Gel) Electrophoresis-Based Methods for Immunoglobulin (G) Glycosylation Analysis.","authors":"Samanta Cajic, René Hennig, Robert Burock, Erdmann Rapp","doi":"10.1007/978-3-030-76912-3_4","DOIUrl":"https://doi.org/10.1007/978-3-030-76912-3_4","url":null,"abstract":"The in-depth characterization of protein glycosylation has become indispensable in many research fields and in the biopharmaceutical industry. Especially knowledge about modulations in immunoglobulin G (IgG) N-glycosylation and their effect on immunity enabled a better understanding of human diseases and the development of new, more effective drugs for their treatment. This chapter provides a deeper insight into capillary (gel) electrophoresis-based (C(G)E) glycan analysis, addressing its impressive performance and possibilities, its great potential regarding real high-throughput for large cohort studies, as well as its challenges and limitations. We focus on the latest developments with respect to miniaturization and mass spectrometry coupling, as well as data analysis and interpretation. The use of exoglycosidase sequencing in combination with current C(G)E technology is discussed, highlighting possible difficulties and pitfalls. The application section describes the detailed characterization of N-glycosylation, utilizing multiplexed CGE with laser-induced fluorescence detection (xCGE-LIF). Besides a comprehensive overview on antibody glycosylation by comparing species-specific IgGs and human immunoglobulins A, D, E, G, and M, the chapter comprises a comparison of therapeutic monoclonal antibodies from different production cell lines, as well as a detailed characterization of Fab and Fc glycosylation. These examples illustrate the full potential of C(G)E, resolving the smallest differences in sugar composition and structure.","PeriodicalId":36906,"journal":{"name":"Experientia supplementum (2012)","volume":"112 ","pages":"137-172"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39549032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Immunoglobulin G Glycosylation in Diseases. 疾病中的免疫球蛋白G糖基化。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_13

Marija Pezer

引用次数: 1

The Rapidly Expanding Nexus of Immunoglobulin G N-Glycomics, Suboptimal Health Status, and Precision Medicine. 免疫球蛋白G - n -糖组学、亚理想健康状态和精准医学之间迅速扩大的联系。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_17

Alyce Russell, Wei Wang

引用次数: 5

Glycosylation of Plant-Produced Immunoglobulins. 植物免疫球蛋白的糖基化。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_16

Kathrin Göritzer, Richard Strasser

{"title":"Glycosylation of Plant-Produced Immunoglobulins.","authors":"Kathrin Göritzer, Richard Strasser","doi":"10.1007/978-3-030-76912-3_16","DOIUrl":"10.1007/978-3-030-76912-3_16","url":null,"abstract":"Many economically important protein-based therapeutics like monoclonal antibodies are glycosylated. Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field. Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity. Apart from producing more effective antibodies, pure glycoforms are required in efforts to link biological functions to specific glycan structures. Much is already known about the role of IgG1 glycosylation and this antibody class is the dominant recombinant format that has been expressed in plants. By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM). Except for IgD, all these antibody classes have been expressed in plants and the glycosylation has been analyzed in a site-specific manner. Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.","PeriodicalId":36906,"journal":{"name":"Experientia supplementum (2012)","volume":"112 ","pages":"519-543"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39568552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic Regulation of Immunoglobulin G Glycosylation. 免疫球蛋白G糖基化的遗传调控。

Experientia supplementum (2012) Pub Date : 2021-01-01 DOI: 10.1007/978-3-030-76912-3_8

Azra Frkatovic, Olga O Zaytseva, Lucija Klaric

{"title":"Genetic Regulation of Immunoglobulin G Glycosylation.","authors":"Azra Frkatovic, Olga O Zaytseva, Lucija Klaric","doi":"10.1007/978-3-030-76912-3_8","DOIUrl":"10.1007/978-3-030-76912-3_8","url":null,"abstract":"Defining the genetic components that control glycosylation of the human immunoglobulin G (IgG) is an ongoing effort, which has so far been addressed by means of heritability, linkage and genome-wide association studies (GWAS). Unlike the synthesis of proteins, N-glycosylation biosynthesis is not a template-driven process, but rather a complex process regulated by both genetic and environmental factors. Current heritability studies have shown that while up to 75% of the variation in levels of some IgG glycan traits can be explained by genetics, some glycan traits are completely defined by environmental influences. Advances in both high-throughput genotyping and glycan quantification methods have enabled genome-wide association studies that are increasingly used to estimate associations of millions of single-nucleotide polymorphisms and glycosylation traits. Using this method, 18 genomic regions have so far been robustly associated with IgG N-glycosylation, discovering associations with genes encoding glycosyltransferases, but also transcription factors, co-factors, membrane transporters and other genes with no apparent role in IgG glycosylation. Further computational analyses have shown that IgG glycosylation is likely to be regulated through the expression of glycosyltransferases, but have also for the first time suggested which transcription factors are involved in the process. Moreover, it was also shown that IgG glycosylation and inflammatory diseases share common underlying causal genetic variants, suggesting that studying genetic regulation of IgG glycosylation helps not only to better understand this complex process but can also contribute to understanding why glycans are changed in disease. However, further studies are needed to unravel whether changes in IgG glycosylation are causing these diseases or the changes in the glycome are caused by the disease.","PeriodicalId":36906,"journal":{"name":"Experientia supplementum (2012)","volume":"112 ","pages":"259-287"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39549035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0