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1
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Marglous S, Brown CE, Padler-Karavani V, Cummings RD, Gildersleeve JC. Serum antibody screening using glycan arrays. Chem Soc Rev 2024; 53:2603-2642. [PMID: 38305761 PMCID: PMC7616341 DOI: 10.1039/d3cs00693j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Humans and other animals produce a diverse collection of antibodies, many of which bind to carbohydrate chains, referred to as glycans. These anti-glycan antibodies are a critical part of our immune systems' defenses. Whether induced by vaccination or natural exposure to a pathogen, anti-glycan antibodies can provide protection against infections and cancers. Alternatively, when an immune response goes awry, antibodies that recognize self-glycans can mediate autoimmune diseases. In any case, serum anti-glycan antibodies provide a rich source of information about a patient's overall health, vaccination history, and disease status. Glycan microarrays provide a high-throughput platform to rapidly interrogate serum anti-glycan antibodies and identify new biomarkers for a variety of conditions. In addition, glycan microarrays enable detailed analysis of the immune system's response to vaccines and other treatments. Herein we review applications of glycan microarray technology for serum anti-glycan antibody profiling.
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Affiliation(s)
- Samantha Marglous
- Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA.
| | - Claire E Brown
- Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA.
| | - Vered Padler-Karavani
- Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.
| | - Richard D Cummings
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA.
| | - Jeffrey C Gildersleeve
- Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA.
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2
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Padoan A, Musso G, Contran N, Basso D. Inflammation, Autoinflammation and Autoimmunity in Inflammatory Bowel Diseases. Curr Issues Mol Biol 2023; 45:5534-5557. [PMID: 37504266 PMCID: PMC10378236 DOI: 10.3390/cimb45070350] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/28/2023] [Accepted: 06/28/2023] [Indexed: 07/29/2023] Open
Abstract
In this review, the role of innate and adaptive immunity in the pathogenesis of inflammatory bowel diseases (IBD) is reported. In IBD, an altered innate immunity is often found, with increased Th17 and decreased Treg cells infiltrating the intestinal mucosa. An associated increase in inflammatory cytokines, such as IL-1 and TNF-α, and a decrease in anti-inflammatory cytokines, such as IL-10, concur in favoring the persistent inflammation of the gut mucosa. Autoinflammation is highlighted with insights in the role of inflammasomes, which activation by exogenous or endogenous triggers might be favored by mutations of NOD and NLRP proteins. Autoimmunity mechanisms also take place in IBD pathogenesis and in this context of a persistent immune stimulation by bacterial antigens and antigens derived from intestinal cells degradation, the adaptive immune response takes place and results in antibodies and autoantibodies production, a frequent finding in these diseases. Inflammation, autoinflammation and autoimmunity concur in altering the mucus layer and enhancing intestinal permeability, which sustains the vicious cycle of further mucosal inflammation.
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Affiliation(s)
- Andrea Padoan
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Giulia Musso
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Nicole Contran
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Daniela Basso
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
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3
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Bakshani CR, Cuskin F, Lant NJ, Yau HCL, Willats WGT, Grant Burgess J. Analysis of glycans in a Burnt-on/Baked-on (BoBo) model food soil using Microarray Polymer Profiling (MAPP) and immunofluorescence microscopy. Food Chem 2023; 410:135379. [PMID: 36621331 DOI: 10.1016/j.foodchem.2022.135379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/12/2022] [Accepted: 12/31/2022] [Indexed: 01/03/2023]
Abstract
Burning of food materials during cooking can increase the difficulty in removal from solid surfaces, forming residual food soils. Using molecular probe-based technologies, the aim of this work was to elucidate the composition and relative abundance of glycans within a Burnt-On/Baked-On (BoBo) model food soil and investigate enzyme systems that may facilitate soil breakdown. Microarray Polymer Profiling identified xylan, arabinoxylan, mixed-linkage glucan and mannan as target substrates for the enzymatic cleaning of BoBo residues from surfaces. Indirect immunofluorescence microscopy revealed that burning resulted in extensive structural modifications and degradation of the three-dimensional architecture of constituent polysaccharide matrices. Results from high-throughput enzyme screening indicate that inclusion of xylan depolymerising enzymes in automatic dishwashing detergents may improve cleaning of recalcitrant, plant glycan-rich BoBo soils. Collectively, this study provides new insight into the composition and removal chemistry of complex, multi-component food soils.
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Affiliation(s)
- Cassie R Bakshani
- School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
| | - Fiona Cuskin
- School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
| | - Neil J Lant
- Procter & Gamble, Newcastle Innovation Centre, Newcastle upon Tyne NE12 9TS, UK
| | - Hamish C L Yau
- Procter & Gamble, Newcastle Innovation Centre, Newcastle upon Tyne NE12 9TS, UK
| | - William G T Willats
- School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
| | - J Grant Burgess
- School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
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4
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Abstract
Through their specific interactions with proteins, cellular glycans play key roles in a wide range of physiological and pathological processes. One of the main goals of research in the areas of glycobiology and glycomedicine is to understand glycan-protein interactions at the molecular level. Over the past two decades, glycan microarrays have become powerful tools for the rapid evaluation of interactions between glycans and proteins. In this review, we briefly describe methods used for the preparation of glycan probes and the construction of glycan microarrays. Next, we highlight applications of glycan microarrays to rapid profiling of glycan-binding patterns of plant, animal and pathogenic lectins, as well as other proteins. Finally, we discuss other important uses of glycan microarrays, including the rapid analysis of substrate specificities of carbohydrate-active enzymes, the quantitative determination of glycan-protein interactions, discovering high-affinity or selective ligands for lectins, and identifying functional glycans within cells. We anticipate that this review will encourage researchers to employ glycan microarrays in diverse glycan-related studies.
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Affiliation(s)
- Yujun Kim
- Department of Chemistry, Yonsei University, 03722 Seoul, Republic of Korea.
| | - Ji Young Hyun
- Department of Drug Discovery, Data Convergence Drug Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of Korea.
| | - Injae Shin
- Department of Chemistry, Yonsei University, 03722 Seoul, Republic of Korea.
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5
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Kadhirvel P, Azenha M, Ivanova G, Pereira C, Silva AF. A simpler and greener alternative route for anchoring carbohydrates with structural integrity on silica and glass supports. J Carbohydr Chem 2022. [DOI: 10.1080/07328303.2022.2121835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Affiliation(s)
- Porkodi Kadhirvel
- CIQ-UP, Departamento de Química e Bioquímica, Faculdade de Ciências, Institute of Molecular Sciences, Universidade do Porto, Porto, Portugal
| | - Manuel Azenha
- CIQ-UP, Departamento de Química e Bioquímica, Faculdade de Ciências, Institute of Molecular Sciences, Universidade do Porto, Porto, Portugal
| | - Galya Ivanova
- Requimte, LAQV, Faculdade de Ciências, Universidade do Porto, Porto, Portugal
| | - Carlos Pereira
- CIQ-UP, Departamento de Química e Bioquímica, Faculdade de Ciências, Institute of Molecular Sciences, Universidade do Porto, Porto, Portugal
| | - António F. Silva
- CIQ-UP, Departamento de Química e Bioquímica, Faculdade de Ciências, Institute of Molecular Sciences, Universidade do Porto, Porto, Portugal
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6
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Temme JS, Crainic JA, Walker LM, Yang W, Tan Z, Huang X, Gildersleeve JC. Microarray-guided evaluation of the frequency, B cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies. J Biol Chem 2022; 298:102468. [PMID: 36087840 PMCID: PMC9576894 DOI: 10.1016/j.jbc.2022.102468] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 09/01/2022] [Accepted: 09/03/2022] [Indexed: 11/28/2022] Open
Abstract
The immune system produces a diverse collection of antiglycan antibodies that are critical for host defense. At present, however, we know very little about the binding properties, origins, and sequences of these antibodies because of a lack of access to a variety of defined individual antibodies. To address this challenge, we used a glycan microarray with over 800 different components to screen a panel of 516 human monoclonal antibodies that had been randomly cloned from different B-cell subsets originating from healthy human subjects. We obtained 26 antiglycan antibodies, most of which bound microbial carbohydrates. The majority of the antiglycan antibodies identified in the screen displayed selective binding for specific glycan motifs on our array and lacked polyreactivity. We found that antiglycan antibodies were about twice as likely than expected to originate from IgG+ memory B cells, whereas none were isolated from naïve, early emigrant, or immature B cells. Therefore, our results indicate that certain B-cell subsets in our panel are enriched in antiglycan antibodies, and IgG+ memory B cells may be a promising source of such antibodies. Furthermore, some of the newly identified antibodies bound glycans for which there are no reported monoclonal antibodies available, and these may be useful as research tools, diagnostics, or therapeutic agents. Overall, the results provide insight into the types and properties of antiglycan antibodies produced by the human immune system and a framework for the identification of novel antiglycan antibodies in the future.
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Affiliation(s)
- J Sebastian Temme
- Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702
| | - Jennifer A Crainic
- Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702
| | - Laura M Walker
- Adimab LLC, Lebanon, NH 03766, USA; Adagio Therapeutics, Inc., Waltham, MA 02451, USA
| | - Weizhun Yang
- Department of Chemistry, Michigan State University, 578 S Shaw Lane, East Lansing, Michigan 48824, United States; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan 48824, USA
| | - Zibin Tan
- Department of Chemistry, Michigan State University, 578 S Shaw Lane, East Lansing, Michigan 48824, United States; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan 48824, USA
| | - Xuefei Huang
- Department of Chemistry, Michigan State University, 578 S Shaw Lane, East Lansing, Michigan 48824, United States; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan 48824, USA; Department of Biomedical Engineering, Michigan State University, East Lansing, Michigan 48824, USA
| | - Jeffrey C Gildersleeve
- Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702.
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Abstract
The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently. The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling. Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors. These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
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Affiliation(s)
- Sachin S Shivatare
- Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA
| | - Chi-Huey Wong
- Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA
- Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
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8
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Luetscher RND, McKitrick TR, Gao C, Mehta AY, McQuillan AM, Kardish R, Boligan KF, Song X, Lu L, Heimburg-Molinaro J, von Gunten S, Alter G, Cummings RD. Unique repertoire of anti-carbohydrate antibodies in individual human serum. Sci Rep 2020; 10:15436. [PMID: 32963315 PMCID: PMC7509809 DOI: 10.1038/s41598-020-71967-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 08/19/2020] [Indexed: 12/13/2022] Open
Abstract
Humoral immunity to pathogens and other environmental challenges is paramount to maintain normal health, and individuals lacking or unable to make antibodies are at risk. Recent studies indicate that many human protective antibodies are against carbohydrate antigens; however, little is known about repertoires and individual variation of anti-carbohydrate antibodies in healthy individuals. Here we analyzed anti-carbohydrate antibody repertoires (ACARs) of 105 healthy individual adult donors, aged 20-60+ from different ethnic backgrounds to explore variations in antibodies, as defined by binding to glycan microarrays and by affinity purification. Using microarrays that contained > 1,000 glycans, including antigens from animal cells and microbes, we profiled the IgG and IgM ACARs from all donors. Each donor expressed many ACAs, but had a relatively unique ACAR, which included unanticipated antibodies to carbohydrate antigens not well studied, such as chitin oligosaccharides, Forssman-related antigens, globo-type antigens, and bacterial glycans. We also saw some expected antibodies to ABO(H) blood group and α-Gal-type antigens, although these also varied among individuals. Analysis suggests differences in ACARs are associated with ethnicity and age. Thus, each individual ACAR is relatively unique, suggesting that individualized information could be useful in precision medicine for predicting and monitoring immune health and resistance to disease.
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Affiliation(s)
- Ralph N D Luetscher
- Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087 - 3 Blackfan Circle, Boston, MA, 02115, USA
- Department of Biology, Institute of Microbiology, ETH Zurich, 8093, Zurich, Switzerland
| | - Tanya R McKitrick
- Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087 - 3 Blackfan Circle, Boston, MA, 02115, USA
| | - Chao Gao
- Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087 - 3 Blackfan Circle, Boston, MA, 02115, USA
| | - Akul Y Mehta
- Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087 - 3 Blackfan Circle, Boston, MA, 02115, USA
| | - Alyssa M McQuillan
- Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087 - 3 Blackfan Circle, Boston, MA, 02115, USA
| | - Robert Kardish
- Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087 - 3 Blackfan Circle, Boston, MA, 02115, USA
- Scienion US, 2640 West Medtronic Way, Tempe, AZ, 85281, USA
| | | | - Xuezheng Song
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30303, USA
| | - Lenette Lu
- The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA
- Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA
| | - Jamie Heimburg-Molinaro
- Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087 - 3 Blackfan Circle, Boston, MA, 02115, USA
| | | | - Galit Alter
- The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA
| | - Richard D Cummings
- Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087 - 3 Blackfan Circle, Boston, MA, 02115, USA.
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9
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Petit B, Mitaine-Offer AC, Fernández FR, Papini AM, Delaude C, Miyamoto T, Tanaka C, Rovero P, Lacaille-Dubois MA. Triterpene glycosides from Blighia welwitschii and evaluation of their antibody recognition capacity in multiple sclerosis. PHYTOCHEMISTRY 2020; 176:112392. [PMID: 32512361 DOI: 10.1016/j.phytochem.2020.112392] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 04/11/2020] [Accepted: 04/15/2020] [Indexed: 06/11/2023]
Abstract
Multiple sclerosis (MS) in a multifactorial autoimmune disease in which reliable biomarkers are needed for therapeutic monitoring and diagnosis. Autoantibodies (autoAbs) are known biomarker candidates although their detection in biological fluids requires a thorough characterization of their associated antigens. Over the past twenty years, a reverse chemical-based approach aiming to screen putative autoantigens has underlined the role of glycans, in particular glucose, in MS. Despite the progress achieved, a lack of consensus regarding the nature of innate antigens as well as difficulties proposing new synthetic glucose-based structures have proved to be obstacles. Here is proposed a strategy to extend the current methodology to the field of natural glycosides, in order to dramatically increase the diversity of glycans that could be tested. Triterpene saponins from the Sapindaceace family represent an optimal starting material as their abundant description in the literature has revealed a prevalence of glucose-based oligosaccharides. Blighia welwitschii (Sapindaceae) was thus selected as a case study and twelve triterpene saponins were isolated and characterized. Their structures were elucidated on the basis of 1D and 2D NMR as well as mass spectrometry, revealing seven undescribed compounds. A selection of natural glycosides exhibiting various oligosaccharide moieties were then tested as antigens in enzyme-linked immunosorbent assay (ELISA) to recognize IgM antibodies (Abs) in MS patients' sera. Immunoassay results indicated a correlation between the glycan structures and their antibody recognition capacity, allowing the determination of structure-activity relationships that were coherent with previous studies. This approach might help to identify sugar epitopes putatively involved in MS pathogenesis, which remains poorly understood.
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Affiliation(s)
- Bastien Petit
- PEPITE EA 4267, Laboratoire de Pharmacognosie, UFR des Sciences de Santé, Université de Bourgogne Franche-Comté, BP 87900, 21079, Dijon, Cedex, France
| | - Anne-Claire Mitaine-Offer
- PEPITE EA 4267, Laboratoire de Pharmacognosie, UFR des Sciences de Santé, Université de Bourgogne Franche-Comté, BP 87900, 21079, Dijon, Cedex, France.
| | - Feliciana Real Fernández
- Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, 50019, Sesto Fiorentino, Italy; Department of Neurosciences, Psychology, Drug Research and Child Health, NeuroFarBa Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, 50019, Sesto Fiorentino, Italy
| | - Anna Maria Papini
- Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, 50019, Sesto Fiorentino, Italy; Department of Chemistry "Ugo Schiff", University of Florence, 50019, Sesto Fiorentino, Italy; Laboratory of Chemical Biology, EA 4505 PeptLab@UCP, University of Cergy Pontoise, 95031, Cergy, Pontoise Cedex, France
| | - Clément Delaude
- Centre de Recherche Phytochimique, Université de Liège, Institut de Chimie-B6, Sart Tilman, B-4000, Liège I, Belgium
| | - Tomofumi Miyamoto
- Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
| | - Chiaki Tanaka
- Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
| | - Paolo Rovero
- Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, 50019, Sesto Fiorentino, Italy; Department of Neurosciences, Psychology, Drug Research and Child Health, NeuroFarBa Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, 50019, Sesto Fiorentino, Italy
| | - Marie-Aleth Lacaille-Dubois
- PEPITE EA 4267, Laboratoire de Pharmacognosie, UFR des Sciences de Santé, Université de Bourgogne Franche-Comté, BP 87900, 21079, Dijon, Cedex, France
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10
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Li Z, Zhang Q, Ashline D, Zhu Y, Lasanajak Y, Chernova T, Reinhold V, Cummings RD, Wang PG, Ju T, Smith DF, Song X. Amplification and Preparation of Cellular O-Glycomes for Functional Glycomics. Anal Chem 2020; 92:10390-10401. [PMID: 32539345 DOI: 10.1021/acs.analchem.0c00632] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Mucin-type O-glycans play key roles in many cellular processes, and they are often altered in human diseases. A major challenge in studying the role of O-glycans through functional O-glycomics is the absence of a complete repertoire of the glycans that comprise the human O-glycome. Here we describe a cellular O-glycome preparation strategy, Preparative Cellular O-Glycome Reporter/Amplification (pCORA), that introduces 4-N3-Bn-GalNAc(Ac)3 as a novel precursor in large-scale cell cultures to generate usable amounts of O-glycans as a potential O-glycome factory. Cultured human non-small cell lung cancer (NSCLC) A549 cells take up the precursor, which is extended by cellular glycosyltransferases to produce 4-N3-Bn-α-O-glycans that are secreted into the culture medium. The O-glycan derivatives can be clicked with a fluorescent bifunctional tag that allows multidimensional HPLC purification and production of a tagged glycan library, representing the O-glycome of the corresponding cells. We obtained ∼5% conversion of precursor to O-glycans and purified a tagged O-glycan library of over 100 O-glycan derivatives, many of which were present in >100 nmol amounts and were sequenced by sequential MS fragmentation (MSn). These O-glycans were successfully printed onto epoxy glass slides as an O-glycome shotgun microarray. We used this novel array to explore binding activity of serum IgM in healthy persons and NSCLC patients at different cancer stages. This novel strategy provides access to complex O-glycans in significant quantities and may offer a new route to discovery of potential diagnostic disease biomarkers.
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Affiliation(s)
| | - Qing Zhang
- Department of Chemistry and Center for Diagnostics & Therapeutics, Georgia State University, 33 Gilmer Street SE, Atlanta, Georgia 30302, United States
| | - David Ashline
- College of Life Sciences and Agriculture, University of New Hampshire, 35 Colovos Road, Durham, New Hampshire 03824, United States
| | | | | | | | - Vernon Reinhold
- College of Life Sciences and Agriculture, University of New Hampshire, 35 Colovos Road, Durham, New Hampshire 03824, United States
| | - Richard D Cummings
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, United States
| | - Peng G Wang
- Department of Chemistry and Center for Diagnostics & Therapeutics, Georgia State University, 33 Gilmer Street SE, Atlanta, Georgia 30302, United States
| | - Tongzhong Ju
- Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10001 New Hampshire Avenue, Silver Spring, Maryland 20993, United States
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11
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Mende M, Bordoni V, Tsouka A, Loeffler FF, Delbianco M, Seeberger PH. Multivalent glycan arrays. Faraday Discuss 2020; 219:9-32. [PMID: 31298252 DOI: 10.1039/c9fd00080a] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Glycan microarrays have become a powerful technology to study biological processes, such as cell-cell interaction, inflammation, and infections. Yet, several challenges, especially in multivalent display, remain. In this introductory lecture we discuss the state-of-the-art glycan microarray technology, with emphasis on novel approaches to access collections of pure glycans and their immobilization on surfaces. Future directions to mimic the natural glycan presentation on an array format, as well as in situ generation of combinatorial glycan collections, are discussed.
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Affiliation(s)
- Marco Mende
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
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12
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Gao C, Wei M, McKitrick TR, McQuillan AM, Heimburg-Molinaro J, Cummings RD. Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins. Front Chem 2019; 7:833. [PMID: 31921763 PMCID: PMC6923789 DOI: 10.3389/fchem.2019.00833] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 11/15/2019] [Indexed: 12/15/2022] Open
Abstract
Glycans and glycan binding proteins (GBPs or lectins) are essential components in almost every aspect of immunology. Investigations of the interactions between glycans and GBPs have greatly advanced our understanding of the molecular basis of these fundamental immunological processes. In order to better study the glycan-GBP interactions, microscope glass slide-based glycan microarrays were conceived and proved to be an incredibly useful and successful tool. A variety of methods have been developed to better present the glycans so that they mimic natural presentations. Breakthroughs in chemical biology approaches have also made available glycans with sophisticated structures that were considered practically impossible just a few decade ago. Glycan microarrays provide a wealth of valuable information in immunological studies. They allow for discovery of detailed glycan binding preferences or novel binding epitopes of known endogenous immune receptors, which can potentially lead to the discovery of natural ligands that carry the glycans. Glycan microarrays also serve as a platform to discover new GBPs that are vital to the process of infection and invasion by microorganisms. This review summarizes the construction strategies and the immunological applications of glycan microarrays, particularly focused on those with the most comprehensive sets of glycan structures. We also review new methods and technologies that have evolved. We believe that glycan microarrays will continue to benefit the growing research community with various interests in the field of immunology.
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Affiliation(s)
| | | | | | | | | | - Richard D. Cummings
- Department of Surgery, National Center for Functional Glycomics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
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13
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Geissner A, Reinhardt A, Rademacher C, Johannssen T, Monteiro J, Lepenies B, Thépaut M, Fieschi F, Mrázková J, Wimmerova M, Schuhmacher F, Götze S, Grünstein D, Guo X, Hahm HS, Kandasamy J, Leonori D, Martin CE, Parameswarappa SG, Pasari S, Schlegel MK, Tanaka H, Xiao G, Yang Y, Pereira CL, Anish C, Seeberger PH. Microbe-focused glycan array screening platform. Proc Natl Acad Sci U S A 2019; 116:1958-1967. [PMID: 30670663 PMCID: PMC6369816 DOI: 10.1073/pnas.1800853116] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Interactions between glycans and glycan binding proteins are essential for numerous processes in all kingdoms of life. Glycan microarrays are an excellent tool to examine protein-glycan interactions. Here, we present a microbe-focused glycan microarray platform based on oligosaccharides obtained by chemical synthesis. Glycans were generated by combining different carbohydrate synthesis approaches including automated glycan assembly, solution-phase synthesis, and chemoenzymatic methods. The current library of more than 300 glycans is as diverse as the mammalian glycan array from the Consortium for Functional Glycomics and, due to its microbial focus, highly complementary. This glycan platform is essential for the characterization of various classes of glycan binding proteins. Applications of this glycan array platform are highlighted by the characterization of innate immune receptors and bacterial virulence factors as well as the analysis of human humoral immunity to pathogenic glycans.
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Affiliation(s)
- Andreas Geissner
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Anika Reinhardt
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Christoph Rademacher
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Timo Johannssen
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - João Monteiro
- Immunology Unit and Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
| | - Bernd Lepenies
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
- Immunology Unit and Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
| | - Michel Thépaut
- Université Grenoble Alpes, Institut de Biologie Structurale, F-38044 Grenoble, France
- CNRS, Institut de Biologie Structurale, F-38044 Grenoble, France
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, F-38044 Grenoble, France
| | - Franck Fieschi
- Université Grenoble Alpes, Institut de Biologie Structurale, F-38044 Grenoble, France
- CNRS, Institut de Biologie Structurale, F-38044 Grenoble, France
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, F-38044 Grenoble, France
| | - Jana Mrázková
- Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic
| | - Michaela Wimmerova
- Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic
| | - Frank Schuhmacher
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Sebastian Götze
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Dan Grünstein
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Xiaoqiang Guo
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Heung Sik Hahm
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | - Jeyakumar Kandasamy
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
| | - Daniele Leonori
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
| | - Christopher E Martin
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
| | | | - Sandip Pasari
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
| | - Mark K Schlegel
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
| | - Hidenori Tanaka
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
| | - Guozhi Xiao
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
| | - You Yang
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
| | - Claney L Pereira
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
| | - Chakkumkal Anish
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
| | - Peter H Seeberger
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany;
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
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14
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Braganza CD, Santoso KT, Dangerfield EM, La Flamme AC, Timmer MSM, Stocker BL. Evaluation of anti α-d-Glcp-(1→4)-α-d-Glcp (GAGA4) IgM antibodies as a biomarker for multiple sclerosis. RSC Adv 2018; 8:28086-28093. [PMID: 35542693 PMCID: PMC9084297 DOI: 10.1039/c8ra04897e] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 07/22/2018] [Indexed: 12/03/2022] Open
Abstract
The correct diagnosis of multiple sclerosis (MS) remains challenging due to the complex pathophysiological and clinical characteristics of the disease. Consequently, there has been immense interest in finding a non-invasive diagnostic test for MS. Recent studies found that serum anti-α-d-Glcp-(1→4)-α-d-Glcp (GAGA4) IgM antibodies were upregulated in MS patients, and this finding led to the development of a commercial diagnostic test (gMS® Dx test), although the test has poor selectivity and has not been independently validated. Herein, we developed an enzyme-linked immunosorbent assay (ELISA) to evaluate the use and reliability of several anti-glucose IgM antibodies, including those against GAGA4, as diagnostic biomarkers for MS. In contrast to previous studies, our results show that serum anti-GAGA4 IgM antibody levels are not significantly higher in MS patients, which could potentially explain the poor selectivity of the commercial test. Anti-glucose IgM antibodies are not upregulated in RRMS patients and thus are not a suitable biomarker for MS.![]()
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Affiliation(s)
- Chriselle D. Braganza
- School of Chemical and Physical Sciences
- Victoria University of Wellington
- Wellington 6140
- New Zealand
- Centre for Biodiscovery
| | - Kristiana T. Santoso
- School of Chemical and Physical Sciences
- Victoria University of Wellington
- Wellington 6140
- New Zealand
- Centre for Biodiscovery
| | - Emma M. Dangerfield
- School of Chemical and Physical Sciences
- Victoria University of Wellington
- Wellington 6140
- New Zealand
- Centre for Biodiscovery
| | - Anne C. La Flamme
- Centre for Biodiscovery
- Victoria University of Wellington
- Wellington 6140
- New Zealand
- Malaghan Institute of Medical Research
| | - Mattie S. M. Timmer
- School of Chemical and Physical Sciences
- Victoria University of Wellington
- Wellington 6140
- New Zealand
- Centre for Biodiscovery
| | - Bridget L. Stocker
- School of Chemical and Physical Sciences
- Victoria University of Wellington
- Wellington 6140
- New Zealand
- Centre for Biodiscovery
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15
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Arnold KB, Chung AW. Prospects from systems serology research. Immunology 2017; 153:279-289. [PMID: 29139548 PMCID: PMC5795183 DOI: 10.1111/imm.12861] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 11/02/2017] [Accepted: 11/04/2017] [Indexed: 12/28/2022] Open
Abstract
Antibodies are highly functional glycoproteins capable of providing immune protection through multiple mechanisms, including direct pathogen neutralization and the engagement of their Fc portions with surrounding effector immune cells that induce anti-pathogenic responses. Small modifications to multiple antibody biophysical features induced by vaccines can significantly alter functional immune outcomes, though it is difficult to predict which combinations confer protective immunity. In order to give insight into the highly complex and dynamic processes that drive an effective humoral immune response, here we discuss recent applications of 'Systems Serology', a new approach that uses data-driven (also called 'machine learning') computational analysis and high-throughput experimental data to infer networks of important antibody features associated with protective humoral immunity and/or Fc functional activity. This approach offers the ability to understand humoral immunity beyond single correlates of protection, assessing the relative importance of multiple biophysical modifications to antibody features with multivariate computational approaches. Systems Serology has the exciting potential to help identify novel correlates of protection from infection and may generate a more comprehensive understanding of the mechanisms behind protection, including key relationships between specific Fc functions and antibody biophysical features (e.g. antigen recognition, isotype, subclass and/or glycosylation events). Reviewed here are some of the experimental and computational technologies available for Systems Serology research and evidence that the application has broad relevance to multiple different infectious diseases including viruses, bacteria, fungi and parasites.
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Affiliation(s)
- Kelly B Arnold
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Amy W Chung
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Vic., Australia
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16
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ImmunoCAP cellulose displays cross-reactive carbohydrate determinant (CCD) epitopes and can cause false-positive test results in patients with high anti-CCD IgE antibody levels. J Allergy Clin Immunol 2017; 141:372-381.e3. [PMID: 28506851 DOI: 10.1016/j.jaci.2017.04.028] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 03/13/2017] [Accepted: 04/12/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Cross-reactive carbohydrate determinants (CCDs) in plants and insect venoms are a common cause of irrelevant positive test results during in vitro allergy diagnosis. We observed that some CCD-positive sera show nonspecific IgE binding even with CCD-free recombinant allergens when using the Phadia ImmunoCAP platform. OBJECTIVE We investigated whether cellulose used as an allergen carrier in ImmunoCAP harbors residual N-glycans, causing nonspecific background binding in CCD-positive sera. METHODS IgE binding to 6 samples of blank ImmunoCAPs coupled to either streptavidin (SA-CAP-1 or 2) or nonallergenic maltose-binding protein (MBP; MBP-CAP-1 to 4) and binding to a panel of 4 recombinant allergens were compared in CCD-positive sera before and after inhibition with a CCD inhibitor (MUXF3-human serum albumin). RESULTS Of 52 CCD-positive sera (bromelain, 1.01-59.6 kilounits of antigen per liter [kUA/L]) tested on SA-CAP-1, 35 (67%) showed IgE binding of greater than 0.35 kUA/L (0.41-4.22 kUA/L). Among those with anti-CCD IgE levels of greater than 7.0 kUA/L, 90% (26/29) were positive. IgE binding to SA-CAP-1 correlated with IgE binding to bromelain (r = 0.68) and was completely abolished by serum preincubation with the CCD inhibitor (n = 15). Binding scores with SA-CAP-2 and MBP-CAP-1 to MBP-CAP-4 were generally lower but strongly correlated with those of SA-CAP-1 and bromelain. IgE reactivity of 10 CCD-positive sera (14.0-52.5 kUA/L) with the recombinant allergens rPhl p 12, rFel d 1, rAra h 2, and rPru p 3 was positive to at least 1 allergen in 8 of 10 (0.36-1.63 kUA/L) and borderline in 2 of 10 (0.21-0.25 kUA/L). Binding correlated with antibody binding to bromelain (r = 0.61) and to all blank ImmunoCAPs (r > 0.90) and could be completely blocked by the CCD inhibitor. Overall, mean background binding to cellulose CCDs corresponded to 2% to 3% of the reactivity seen with bromelain. CONCLUSIONS Cellulose used as a solid-phase allergen carrier can contain varying amounts of CCDs sufficient to cause false-positive test results up to 2 kUA/L with nonglycosylated recombinant allergens in patients with high levels of anti-CCD IgE antibodies.
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17
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Jebali A, Nayeri EK, Roohana S, Aghaei S, Ghaffari M, Daliri K, Fuente G. Nano-carbohydrates: Synthesis and application in genetics, biotechnology, and medicine. Adv Colloid Interface Sci 2017; 240:1-14. [PMID: 27988019 DOI: 10.1016/j.cis.2016.11.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Revised: 11/03/2016] [Accepted: 11/04/2016] [Indexed: 01/08/2023]
Abstract
Combining nanoparticles with carbohydrate has triggered an exponential growth of research activities for the design of novel functional bionanomaterials, nano-carbohydrates. Recent advances in versatile synthesis of glycosylated nanoparticles have paved the way towards diverse biomedical applications. The accessibility of a wide variety of these structured nanosystems, in terms of shape, size, and organization around stable nanoparticles, has readily contributed to their development and application in nanomedicine. Glycosylated gold nanoparticles, glycosylated quantum dots, fullerenes, single-wall nanotubes, and self-assembled glyconanoparticles using amphiphilic glycopolymers or glycodendrimers have received considerable attention for their application in powerful imaging, therapeutic, and biodiagnostic devices. Recently, nano-carbohydrates were used for different types of microarrays to detect proteins and nucleic acids.
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Affiliation(s)
- Ali Jebali
- Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran
| | - Elham Khajeh Nayeri
- Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran; Department of Biology, Ashkezar Branch, Islamic Azad University, Ashkezar, Iran
| | - Sima Roohana
- Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran; Department of Biology, Ashkezar Branch, Islamic Azad University, Ashkezar, Iran
| | - Shiva Aghaei
- Department of Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Maede Ghaffari
- Department of Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Karim Daliri
- Department of Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Garcia Fuente
- Department of Nanobiotechnology, Institute of Advanced Tech, Barcelona, Spain.
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18
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19
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Liu Y, McBride R, Stoll M, Palma AS, Silva L, Agravat S, Aoki-Kinoshita KF, Campbell MP, Costello CE, Dell A, Haslam SM, Karlsson NG, Khoo KH, Kolarich D, Novotny MV, Packer NH, Ranzinger R, Rapp E, Rudd PM, Struwe WB, Tiemeyer M, Wells L, York WS, Zaia J, Kettner C, Paulson JC, Feizi T, Smith DF. The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting glycan microarray-based data. Glycobiology 2016; 27:280-284. [PMID: 27993942 PMCID: PMC5444268 DOI: 10.1093/glycob/cww118] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 11/14/2016] [Accepted: 11/21/2016] [Indexed: 11/12/2022] Open
Abstract
MIRAGE (Minimum Information Required for AGlycomics Experiment) is an initiative that was created by experts in the fields of glycobiology, glycoanalytics and glycoinformatics to produce guidelines for reporting results from the diverse types of experiments and analyses used in structural and functional studies of glycans in the scientific literature. As a sequel to the guidelines for sample preparation (Struwe et al. 2016, Glycobiology, 26:907–910) and mass spectrometry data (Kolarich et al. 2013, Mol. Cell Proteomics, 12:991–995), here we present the first version of guidelines intended to improve the standards for reporting data from glycan microarray analyses. For each of eight areas in the workflow of a glycan microarray experiment, we provide guidelines for the minimal information that should be provided in reporting results. We hope that the MIRAGE glycan microarray guidelines proposed here will gain broad acceptance by the community, and will facilitate interpretation and reproducibility of the glycan microarray results with implications in comparison of data from different laboratories and eventual deposition of glycan microarray data in international databases.
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Affiliation(s)
- Yan Liu
- Department of Medicine, Glycosciences Laboratory, Imperial College London, Du Cane Road, London W12 0NN, UK
| | - Ryan McBride
- Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
| | - Mark Stoll
- Department of Medicine, Glycosciences Laboratory, Imperial College London, Du Cane Road, London W12 0NN, UK
| | - Angelina S Palma
- Department of Medicine, Glycosciences Laboratory, Imperial College London, Du Cane Road, London W12 0NN, UK.,Department of Chemistry, UCIBIO@REQUIMTE, Faculty of Science and Technology, NOVA University of Lisbon, Caparica 2829-516, Portugal
| | - Lisete Silva
- Department of Medicine, Glycosciences Laboratory, Imperial College London, Du Cane Road, London W12 0NN, UK
| | - Sanjay Agravat
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Kiyoko F Aoki-Kinoshita
- Department of Science and Engineering for Sustainable Innovation, Faculty of Science and Engineering, Soka University, 1-236 Tangimachi, Hachioji, Tokyo 192-8577, Japan
| | - Matthew P Campbell
- Biomolecular Frontiers Research Centre, Macquarie University, Sydney, NSW 2109, Australia
| | - Catherine E Costello
- Department of Biochemistry, Center for Biomedical Mass Spectrometry, Boston University, School of Medicine, 670 Albany Street, Suite 504, Boston, MA 02118, USA
| | - Anne Dell
- Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK
| | - Stuart M Haslam
- Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK
| | - Niclas G Karlsson
- Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, PO Box 440, 405 30 Gothenburg, Sweden
| | - Kay-Hooi Khoo
- Institute of Biological Chemistry, Academia Sinica, 128, Academia Road Sec. 2, Nankang, Taipei 115, Taiwan
| | - Daniel Kolarich
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam 14424, Germany
| | - Milos V Novotny
- Department of Chemistry, Indiana University, 800 E. Kirkwood Avenue, Bloomington, IN 47405, USA
| | - Nicolle H Packer
- Biomolecular Frontiers Research Centre, Macquarie University, Sydney, NSW 2109, Australia
| | - Rene Ranzinger
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA
| | - Erdmann Rapp
- Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering, 39106 Magdeburg, Germany
| | - Pauline M Rudd
- NIBRT GlycoScience Group, NIBRT-National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co., Dublin, Ireland
| | - Weston B Struwe
- Department of Biochemistry, Glycobiology Institute, University of Oxford, Oxford OX1 3QU, UK
| | - Michael Tiemeyer
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA
| | - Lance Wells
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA
| | - William S York
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA
| | - Joseph Zaia
- Department of Biochemistry, Center for Biomedical Mass Spectrometry, Boston University, School of Medicine, 670 Albany Street, Suite 504, Boston, MA 02118, USA
| | - Carsten Kettner
- Beilstein-Institut, Trakehner Str. 7-9, 60487 Frankfurt am Main, Germany
| | - James C Paulson
- Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
| | - Ten Feizi
- Department of Medicine, Glycosciences Laboratory, Imperial College London, Du Cane Road, London W12 0NN, UK.,Department of Medicine, Glycosciences Laboratory, Imperial College London, Du Cane Road, London W12 0NN, UK
| | - David F Smith
- Emory Comprehensive Glycomics Core, Emory University School of Medicine, Atlanta, GA 30322, USA
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Zhang H, Wang B, Ma Z, Wei M, Liu J, Li D, Zhang H, Wang PG, Chen M. l-Rhamnose Enhances the Immunogenicity of Melanoma-Associated Antigen A3 for Stimulating Antitumor Immune Responses. Bioconjug Chem 2016; 27:1112-8. [DOI: 10.1021/acs.bioconjchem.6b00081] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Huajie Zhang
- National Glycoengineering Research Center, the State Key Laboratory of Microbial Technology and School of Life Science, Shandong University, Jinan, Shandong 250100, China
| | - Bin Wang
- National Glycoengineering Research Center, the State Key Laboratory of Microbial Technology and School of Life Science, Shandong University, Jinan, Shandong 250100, China
| | - Zhongrui Ma
- National Glycoengineering Research Center, the State Key Laboratory of Microbial Technology and School of Life Science, Shandong University, Jinan, Shandong 250100, China
| | - Mohui Wei
- Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, United States
| | - Jun Liu
- National Glycoengineering Research Center, the State Key Laboratory of Microbial Technology and School of Life Science, Shandong University, Jinan, Shandong 250100, China
| | - Dong Li
- Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China
| | - Houcheng Zhang
- National Glycoengineering Research Center, the State Key Laboratory of Microbial Technology and School of Life Science, Shandong University, Jinan, Shandong 250100, China
| | - Peng George Wang
- National Glycoengineering Research Center, the State Key Laboratory of Microbial Technology and School of Life Science, Shandong University, Jinan, Shandong 250100, China
- Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, United States
| | - Min Chen
- National Glycoengineering Research Center, the State Key Laboratory of Microbial Technology and School of Life Science, Shandong University, Jinan, Shandong 250100, China
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21
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Macrophage-Targeting Gene Delivery Using a Micelle Composed of Mannose-Modified Lipid with Triazole Ring and Dioleoyl Trimethylammonium Propane. BIOMED RESEARCH INTERNATIONAL 2015; 2015:350580. [PMID: 26509149 PMCID: PMC4609769 DOI: 10.1155/2015/350580] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Accepted: 05/28/2015] [Indexed: 01/08/2023]
Abstract
Gene carriers with cell specific ligand molecules are needed for the treatment of several diseases. Mannose is known to be recognized and incorporated into the cells through mannose recognition lectins that are exclusively expressed on macrophages. In this study, we synthesized two types of mannose-modified lipids with different stereoisomer (α-mannose and β-mannose). To make a complex with plasmid DNA (pDNA), termed “lipoplex,” we prepared a two-component micelle made from cationic lipid; dioleoyltrimethylammoniumpropane (DOTAP); and mannose-modified lipid (D/α-Man or D/β-Man). The prepared D/α-Man lipoplexes were able to bind to one of the α-mannose lectins concanavalin A (ConA) immobilized on gold substrate in the quartz-crystal microbalance sensor cell. D/β-Man lipoplexes did not show any frequency changes. These results indicate that the mannose residues were exposed on the lipoplexes, leading to not only the binding to ConA but also the prevention of nonspecific interactions with proteins. Both lipoplexes showed high transfection efficiencies to RAW264.7 cells which have several kinds of mannose lectins. This delivery system to macrophages may overcome the problems for gene therapy and may be used for the treatment of immune diseases involved in macrophages.
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22
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Narla SN, Nie H, Li Y, Sun XL. Multi-dimensional glycan microarrays with glyco-macroligands. Glycoconj J 2015; 32:483-95. [PMID: 25957565 DOI: 10.1007/s10719-015-9580-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/06/2015] [Accepted: 03/10/2015] [Indexed: 01/16/2023]
Abstract
Glycan microarray has become a powerful high-throughput tool for examining binding interactions of carbohydrates with the carbohydrate binding biomolecules like proteins, enzymes, antibodies etc. It has shown great potential for biomedical research and applications, such as antibody detection and profiling, vaccine development, biomarker discovery, and drug screening. Most glycan microarrays were made with monovalent glycans immobilized directly onto the array surface via either covalent or non-covalent bond, which afford a multivalent glycans in two dimensional (2D) displaying. A variety of glyco-macroligands have been developed to mimic multivalent carbohydrate-protein interactions for studying carbohydrate-protein interactions and biomedical research and applications. Recently, a number of glyco-macroligands have been explored for glycan microarray fabrication, in particular to mimick the three dimensional (3D) multivalent display of cell surface carbohydrates. This review highlights these recent developments of glyco-macroligand-based microarrays, predominantly, novel glycan microarrays with glyco-macroligands like glycodendrimers, glycopolymers, glycoliposomes, neoglycoproteins, and glyconanoparticles with the effort in controlling the density and orientation of glycans on the array surface, which facilitate both their binding specificity and affinity and thus the high performance of glycan microarrays.
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Affiliation(s)
- Satya Nandana Narla
- Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, 2121 Euclid Avenue, Cleveland, OH, 44115, USA
| | - Huan Nie
- Department of Life Science and Engineering, Harbin Institute of Technology, Harbin, China, 150001
| | - Yu Li
- Department of Life Science and Engineering, Harbin Institute of Technology, Harbin, China, 150001
| | - Xue-Long Sun
- Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, 2121 Euclid Avenue, Cleveland, OH, 44115, USA.
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23
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Long DE, Karmakar P, Wall KA, Sucheck SJ. Synthesis of α-L-rhamnosyl ceramide and evaluation of its binding with anti-rhamnose antibodies. Bioorg Med Chem 2014; 22:5279-89. [PMID: 25172148 DOI: 10.1016/j.bmc.2014.08.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Accepted: 08/02/2014] [Indexed: 11/28/2022]
Abstract
An α-L-rhamnosyl ceramide (1, α-L-RhaCer) has been prepared that was recognized by anti-L-rhamnose (anti-Rha) antibodies. During these studies we explored the use of an α-L-rhamnosyl thioglycoside and a trichloroacetimidate as a glycosyl donors. Subsequently, the acceptors desired for glycosylation, 3-O-benzoylazidosphingosine or 3-O-alloxycarbonylsphingosine, were prepared from D-xylose. The thioglycoside donor, 2,3,4-tri-O-acetyl-1-(4-tolyl)thio-α-L-rhamnopyranoside, and the trichloroacetimidate donor, 2,3,4-tri-O-acetyl-1-(2,2,2-trichloroethanimidate)-α-L-rhamnopyranoside, were synthesized in 50% and 78% yield overall, respectively. The synthesis of the glycosylation acceptor employed an addition-fragmentation olefination that was successfully carried out in 53% yield. With the successful synthesis of key intermediates, α-L-RhaCer (1) was prepared without any insurmountable obstacles. Anti-Rha antibodies were prepared in BALB/c mice by immunizing them with rhamnose-ovalbumin (Rha-Ova) with Sigma Adjuvant System (SAS) and the anti-L-Rha antibodies were isolated from the blood sera. Liposomes and EL4 tumor cells were used as model systems to demonstrate the ability of 1 to insert into a lipid bilayer. The interaction of the liposomes or the EL4 cells with α-L-RhaCer (1) and anti-Rha antibodies were investigated by fluorescence microscopy and flow cytometry, respectively, to confirm the ability of glycolipid 1 to be displayed on the tumor cell surface as well as the ability to be recognized by anti-Rha antibodies.
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Affiliation(s)
- David E Long
- Department of Chemistry, The University of Toledo, 2801 W. Bancroft Street, MS602, Toledo, OH 43606, United States
| | - Partha Karmakar
- Department of Chemistry, The University of Toledo, 2801 W. Bancroft Street, MS602, Toledo, OH 43606, United States
| | - Katherine A Wall
- Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 W. Bancroft Street, MS602, Toledo, OH 43606, United States.
| | - Steven J Sucheck
- Department of Chemistry, The University of Toledo, 2801 W. Bancroft Street, MS602, Toledo, OH 43606, United States.
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24
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Wang D, Bhat R, Sobel RA, Huang W, Wang LX, Olsson T, Steinman L. Uncovering cryptic glycan markers in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Drug Dev Res 2014; 75:172-88. [PMID: 24648292 DOI: 10.1002/ddr.21169] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Accepted: 02/10/2014] [Indexed: 01/18/2023]
Abstract
Using an integrated antigen microarray approach, we observed epitope-spreading of autoantibody responses to a variety of antigenic structures in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and in the serum of mice with experimental autoimmune encephalomyelitis (EAE). These included previously described protein- and lipid-based antigenic targets and newly discovered autoimmunogenic sugar moieties, notably, autoantibodies specific for the oligomannoses in both MS patient CSF and the sera of mice with EAE. These glycans are often masked by other sugar moieties and belong to a class of cryptic autoantigens. We further determined that these targets are highly expressed on multiple cell types in MS and EAE lesions. Co-immunization of SJL/J mice with a Man9-KLH conjugate at the time of EAE induction elicited highly significant levels of anti-Man9-cluster autoantibodies. Nevertheless, this anti-glycan autoantibody response was associated with a significantly reduced clinical severity of EAE. The potential of these cryptic glycan markers and targeting antibodies for diagnostic and therapeutic interventions of neurological disorders has yet to be explored.
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Affiliation(s)
- Denong Wang
- Tumor Glycomics Laboratory, SRI International Biosciences Division, Menlo Park, CA, 94025, USA
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25
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Prideaux L, Kamm MA, De Cruz P, van Langenberg DR, Ng SC, Dotan I. Inflammatory bowel disease serology in Asia and the West. World J Gastroenterol 2013; 19:6207-6213. [PMID: 24115818 PMCID: PMC3787351 DOI: 10.3748/wjg.v19.i37.6207] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Revised: 07/13/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To study serological antibodies in Caucasians and Asians, in health and inflammatory bowel disease (IBD), in Australia and Hong Kong (HK).
METHODS: Anti-glycan antibodies [anti-chitobioside (ACCA), anti-laminaribioside (ALCA)], and anti-mannobioside (AMCA), anti-Saccharomyces cervisiae (gASCA); and atypical perinuclear anti-neutrophil cytoplasmic antibody (pANCA) were tested in IBD patients, their unaffected relatives, and healthy controls in Australia and HK (China). Antibody status (positive or negative) and titre was compared between subjects of different geography, ethnicity and disease state.
RESULTS: Ninety subjects were evaluated: 21 Crohn’s disease (CD), 32 ulcerative colitis (UC), 29 healthy controls, and 8 IBD patient relatives. Forty eight subjects were Australian (29 Caucasian and 19 ethnic Han Chinese) and 42 were from HK (all Han Chinese). Caucasian CD patients had a significantly higher antibody prevalence of gASCA (67% vs 3%, P < 0.001), ALCA (44% vs 6%, P = 0.005), and AMCA (67% vs 15%, P = 0.002), whereas HK CD patients had a higher prevalence of only AMCA (58% vs 25%, P = 0.035), when compared with UC and healthy subjects in both countries. Caucasian CD had significantly higher gASCA prevalence (67% vs 0%, P < 0.001) and titre (median 59 vs 9, P = 0.002) than HK CD patients. Prevalence and titres of ALCA, ACCA and AMCA did not differ between CD in the two countries. Presence of at least one antibody was higher in Caucasian than HK CD patients (100% vs 58%, P = 0.045). pANCA did not differ between countries or ethnicity.
CONCLUSION: Serologic CD responses differ between HK Asian and Australian Caucasian patients. Different genetic, environmental or disease pathogenic factors may account for these differences.
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26
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Campbell CT, Llewellyn SR, Damberg T, Morgan IL, Robert-Guroff M, Gildersleeve JC. High-throughput profiling of anti-glycan humoral responses to SIV vaccination and challenge. PLoS One 2013; 8:e75302. [PMID: 24086502 PMCID: PMC3781036 DOI: 10.1371/journal.pone.0075302] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2013] [Accepted: 08/13/2013] [Indexed: 11/18/2022] Open
Abstract
Recent progress toward an HIV vaccine highlights both the potential of vaccines to end the AIDS pandemic and the need to boost efficacy by incorporating additional vaccine strategies. Although many aspects of the immune response can contribute to vaccine efficacy, the key factors have not been defined fully yet. A particular area that may yield new insights is anti-glycan immune responses, such as those against the glycan shield that HIV uses to evade the immune system. In this study, we used glycan microarray technology to evaluate anti-glycan antibody responses induced by SIV vaccination and infection in a non-human primate model of HIV infection. This comprehensive profiling of circulating anti-glycan antibodies found changes in anti-glycan antibody levels after both vaccination with the Ad5hr-SIV vaccine and SIV infection. Notably, SIV infection produced generalized declines in anti-glycan IgM antibodies in a number of animals. Additionally, some infected animals generated antibodies to the Tn antigen, which is a cryptic tumor-associated antigen exposed by premature termination of O-linked glycans; however, the Ad5hr-SIV vaccine did not induce anti-Tn IgG antibodies. Overall, this study demonstrates the potential contributions that glycan microarrays can make for HIV vaccine development.
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Affiliation(s)
- Christopher T. Campbell
- Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland, United States of America
| | - Sean R. Llewellyn
- Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland, United States of America
| | - Thorsten Damberg
- Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Ian L. Morgan
- Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Marjorie Robert-Guroff
- Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
- * E-mail: (JCG); (MR)
| | - Jeffrey C. Gildersleeve
- Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland, United States of America
- * E-mail: (JCG); (MR)
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Abstract
In the last decade, carbohydrate microarrays have been core technologies for analyzing carbohydrate-mediated recognition events in a high-throughput fashion. A number of methods have been exploited for immobilizing glycans on the solid surface in a microarray format. This microarray-based technology has been widely employed for rapid analysis of the glycan binding properties of lectins and antibodies, the quantitative measurements of glycan-protein interactions, detection of cells and pathogens, identification of disease-related anti-glycan antibodies for diagnosis, and fast assessment of substrate specificities of glycosyltransferases. This review covers the construction of carbohydrate microarrays, detection methods of carbohydrate microarrays and their applications in biological and biomedical research.
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Affiliation(s)
- Sungjin Park
- National Creative Research Initiative Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 120-749, Korea
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28
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Arrambide G, Espejo C, Yarden J, Fire E, Spector L, Dotan N, Dukler A, Rovira A, Montalban X, Tintore M. Serum biomarker gMS-Classifier2: predicting conversion to clinically definite multiple sclerosis. PLoS One 2013; 8:e59953. [PMID: 23555846 PMCID: PMC3610690 DOI: 10.1371/journal.pone.0059953] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2012] [Accepted: 02/20/2013] [Indexed: 12/28/2022] Open
Abstract
Background Anti-glycan antibodies can be found in autoimmune diseases. IgM against glycan P63 was identified in clinically isolated syndromes (CIS) and included in gMS-Classifier2, an algorithm designed with the aim of identifying patients at risk of a second demyelinating attack. Objective To determine the value of gMS-Classifier2 as an early and independent predictor of conversion to clinically definite multiple sclerosis (CDMS). Methods Data were prospectively acquired from a CIS cohort. gMS-Classifier2 was determined in patients first seen between 1995 and 2007 with ≥ two 200 µL serum aliquots (N = 249). The primary endpoint was time to conversion to CDMS at two years, the factor tested was gMS-Classifier2 status (positive/negative) or units; other exploratory time points were 5 years and total time of follow-up. Results Seventy-five patients (30.1%) were gMS-Classifier2 positive. Conversion to CDMS occurred in 31/75 (41.3%) of positive and 45/174 (25.9%) of negative patients (p = 0.017) at two years. Median time to CDMS was 37.8 months (95% CI 10.4–65.3) for positive and 83.9 months (95% CI 57.5–110.5) for negative patients. gMS-Classifier2 status predicted conversion to CDMS within two years of follow-up (HR = 1.8, 95% CI 1.1–2.8; p = 0.014). gMS-Classifier2 units were also independent predictors when tested with either Barkhof criteria and OCB (HR = 1.2, CI 1.0–1.5, p = 0.020) or with T2 lesions and OCB (HR = 1.3, CI 1.1–1.5, p = 0.008). Similar results were obtained at 5 years of follow-up. Discrimination measures showed a significant change in the area under the curve (ΔAUC) when adding gMS-Classifier2 to a model with either Barkhof criteria (ΔAUC 0.0415, p = 0.012) or number of T2 lesions (ΔAUC 0.0467, p = 0.009), but not when OCB were added to these models. Conclusions gMS-Classifier2 is an independent predictor of early conversion to CDMS and could be of clinical relevance, particularly in cases in which OCB are not available.
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Affiliation(s)
- Georgina Arrambide
- Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Carmen Espejo
- Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jennifer Yarden
- Department of Research and Development, Glycominds, Modi’in, Israel
| | - Ella Fire
- Department of Research and Development, Glycominds, Modi’in, Israel
| | - Larissa Spector
- Department of Research and Development, Glycominds, Modi’in, Israel
| | - Nir Dotan
- Department of Research and Development, Glycominds, Modi’in, Israel
| | - Avinoam Dukler
- Department of Research and Development, Glycominds, Simi Valley, California, United States of America
| | - Alex Rovira
- Magnetic Resonance Unit (IDI), Vall d’Hebron University Hospital, Barcelona, Spain
| | - Xavier Montalban
- Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mar Tintore
- Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
- * E-mail:
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29
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Tumor-associated glycans and their role in gynecological cancers: accelerating translational research by novel high-throughput approaches. Metabolites 2012; 2:913-39. [PMID: 24957768 PMCID: PMC3901231 DOI: 10.3390/metabo2040913] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Revised: 11/08/2012] [Accepted: 11/09/2012] [Indexed: 02/06/2023] Open
Abstract
Glycans are important partners in many biological processes, including carcinogenesis. The rapidly developing field of functional glycomics becomes one of the frontiers of biology and biomedicine. Aberrant glycosylation of proteins and lipids occurs commonly during malignant transformation and leads to the expression of specific tumor-associated glycans. The appearance of aberrant glycans on carcinoma cells is typically associated with grade, invasion, metastasis and overall poor prognosis. Cancer-associated carbohydrates are mostly located on the surface of cancer cells and are therefore potential diagnostic biomarkers. Currently, there is increasing interest in cancer-associated aberrant glycosylation, with growing numbers of characteristic cancer targets being detected every day. Breast and ovarian cancer are the most common and lethal malignancies in women, respectively, and potential glycan biomarkers hold promise for early detection and targeted therapies. However, the acceleration of research and comprehensive multi-target investigation of cancer-specific glycans could only be successfully achieved with the help of a combination of novel high-throughput glycomic approaches.
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30
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Prideaux L, De Cruz P, Ng SC, Kamm MA. Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis 2012; 18:1340-55. [PMID: 22069240 DOI: 10.1002/ibd.21903] [Citation(s) in RCA: 137] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Accepted: 08/25/2011] [Indexed: 12/13/2022]
Abstract
The diagnosis of inflammatory bowel disease (IBD) is traditionally based on a combination of clinical, endoscopic, histological, and radiological criteria. However, further testing is needed in cases of diagnostic uncertainty and in predicting disease course. This systematic review focuses on the potential for 10 serological antibodies to fill these roles: pANCA, ASCA, anti-OmpC, anti-CBir1, anti-I2, ALCA, ACCA, AMCA, anti-L, and anti-C. We discuss their prevalence in IBD and health; their role in disease diagnosis and risk stratification; their stability over time; their presence in unaffected relatives; their association with genetic variants; and differences across ethnic groups. Serological antibodies have some role in primary diagnosis and in differentiating between Crohn's disease and ulcerative colitis. In indeterminate colitis, preoperative measurement of serological antibodies can help to predict the likelihood of complications among patients undergoing pouch surgery. The combined presence and magnitude of a large panel of antibodies appear to be of value in predicting disease progression. There is currently insufficient evidence to recommend the use of antibody testing to predict responses to treatment or surgery in patients with IBD.
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Affiliation(s)
- Lani Prideaux
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Australia
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31
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Liang K, Chen Y. Elegant Chemistry to Directly Anchor Intact Saccharides on Solid Surfaces Used for the Fabrication of Bioactivity-Conserved Saccharide Microarrays. Bioconjug Chem 2012; 23:1300-8. [DOI: 10.1021/bc300142s] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Kai Liang
- Key Laboratory of
Analytical
Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
| | - Yi Chen
- Key Laboratory of
Analytical
Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
- Beijing National Laboratory for Molecular Science, Beijing 100190, China
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32
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Morvan F, Vidal S, Souteyrand E, Chevolot Y, Vasseur JJ. DNA glycoclusters and DNA-based carbohydrate microarrays: From design to applications. RSC Adv 2012. [DOI: 10.1039/c2ra21550k] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
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33
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Freedman MS, Metzig C, Kappos L, Polman CH, Edan G, Hartung HP, Miller DH, Montalban X, Yarden J, Spector L, Fire E, Dotan N, Schwenke S, Lanius V, Sandbrink R, Pohl C. Predictive nature of IgM anti-α-glucose serum biomarker for relapse activity and EDSS progression in CIS patients: a BENEFIT study analysis. Mult Scler 2011; 18:966-73. [PMID: 22183938 PMCID: PMC3546632 DOI: 10.1177/1352458511432327] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background: Higher serum levels of at least one of a panel of four α-glucose IgM antibodies (gMS-Classifier1) in clinically isolated syndrome (CIS) patients are associated with imminent early relapse within 2 years. Objective: The objective of this study was to determine the prognostic value of gMS-Classifier1 in a large study cohort of CIS patients. Methods: The BEtaseron® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) 5-year study was designed to evaluate the impact of early versus delayed interferon-β-1b (IFNβ-1b; Betaseron®) treatment in patients with a first event suggestive of multiple sclerosis (MS). Patients (n = 258, 61% of total) with a minimum of 2 ml baseline serum were eligible for the biomarker study. gMS-Classifier1 antibodies’ panel (anti-GAGA2, anti-GAGA3, anti-GAGA4 and anti-GAGA6) levels were measured blinded to clinical data. Subjects were classified as either ‘positive’ or ‘negative’ according to a classification rule. Results: gMS-Classifier1 was not predictive for the time to clinically definite MS or time to MS according to the revised McDonald’s criteria, but did significantly predict an increased risk for confirmed disability progression (log-rank test: p = 0.012). Conclusions: We could not confirm previous results that gMS-Classifier1 can predict early conversion to MS in CIS. However, raised titres of these antibodies may predict early disability progression in this patient population.
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Affiliation(s)
- M S Freedman
- Multiple Sclerosis Research Clinic, The Ottawa Hospital - General Campus, Ottawa, Ontario, Canada.
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Hsu CH, Hung SC, Wu CY, Wong CH. Toward automated oligosaccharide synthesis. Angew Chem Int Ed Engl 2011; 50:11872-923. [PMID: 22127846 DOI: 10.1002/anie.201100125] [Citation(s) in RCA: 208] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Indexed: 12/16/2022]
Abstract
Carbohydrates have been shown to play important roles in biological processes. The pace of development in carbohydrate research is, however, relatively slow due to the problems associated with the complexity of carbohydrate structures and the lack of general synthetic methods and tools available for the study of this class of biomolecules. Recent advances in synthesis have demonstrated that many of these problems can be circumvented. In this Review, we describe the methods developed to tackle the problems of carbohydrate-mediated biological processes, with particular focus on the issue related to the development of the automated synthesis of oligosaccharides. Further applications of carbohydrate microarrays and vaccines to human diseases are also highlighted.
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Affiliation(s)
- Che-Hsiung Hsu
- The Genomics Research Center, Academia Sinica, Taipei, Taiwan
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35
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Hsu CH, Hung SC, Wu CY, Wong CH. Auf dem Weg zur automatisierten Oligosaccharid- Synthese. Angew Chem Int Ed Engl 2011. [DOI: 10.1002/ange.201100125] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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36
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Abstract
In the last decade, glycan microarrays have revolutionized the analysis of the specificity of glycan-binding proteins (GBPs), providing information that simultaneously illuminates the biology mediated by them and decodes the informational content of the glycome. Numerous methods have emerged for arraying glycans in a "chip" format, and glycan libraries have been assembled that address the diversity of the human glycome. Such arrays have been successfully used for analysis of GBPs, which mediate mammalian biology, host-pathogen interactions, and immune recognition of glycans relevant to vaccine production and cancer antigens. This review covers the development of glycan microarrays and applications that have provided insights into the roles of mammalian and microbial GBPs.
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Affiliation(s)
- Cory D Rillahan
- Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA.
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37
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Abstract
Glycan microarrays are emerging as increasingly used screening tools with a high potential for unraveling protein-carbohydrate interactions: probing hundreds or even thousands of glycans in parallel, they provide the researcher with a vast amount of data in a short time-frame, while using relatively small amounts of analytes. Natural glycan microarrays focus on the glycans' repertoire of natural sources, including both well-defined structures as well as still-unknown ones. This article compares different natural glycan microarray strategies. Glycan probes may comprise oligosaccharides from glycoproteins as well as glycolipids and polysaccharides. Oligosaccharides may be purified from scarce biological samples that are of particular relevance for the carbohydrate-binding protein to be studied. We give an overview of strategies for glycan isolation, derivatization, fractionation, immobilization and structural characterization. Detection methods such as fluorescence analysis and surface plasmon resonance are summarized. The importance of glycan density and multivalency is discussed. Furthermore, some applications of natural glycan microarrays for studying lectin and antibody binding are presented.
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Affiliation(s)
- Emanuela Lonardi
- Biomolecular Mass Spectrometry Unit, Department of Parasitology, PO Box 9600, 2300 RC Leiden, The Netherlands
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38
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Sarkar S, Lombardo SA, Herner DN, Talan RS, Wall KA, Sucheck SJ. Synthesis of a Single-Molecule l-Rhamnose-Containing Three-Component Vaccine and Evaluation of Antigenicity in the Presence of Anti-l-Rhamnose Antibodies. J Am Chem Soc 2010; 132:17236-46. [PMID: 21080675 DOI: 10.1021/ja107029z] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Sourav Sarkar
- Department of Chemistry and Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 West Bancroft Street, Toledo, Ohio 43606, United States
| | - Steven A. Lombardo
- Department of Chemistry and Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 West Bancroft Street, Toledo, Ohio 43606, United States
| | - Danielle N. Herner
- Department of Chemistry and Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 West Bancroft Street, Toledo, Ohio 43606, United States
| | - Rommel S. Talan
- Department of Chemistry and Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 West Bancroft Street, Toledo, Ohio 43606, United States
| | - Katherine A. Wall
- Department of Chemistry and Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 West Bancroft Street, Toledo, Ohio 43606, United States
| | - Steven J. Sucheck
- Department of Chemistry and Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 West Bancroft Street, Toledo, Ohio 43606, United States
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Katrlík J, Svitel J, Gemeiner P, Kozár T, Tkac J. Glycan and lectin microarrays for glycomics and medicinal applications. Med Res Rev 2010; 30:394-418. [PMID: 20099267 DOI: 10.1002/med.20195] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Three different array formats to study a challenging field of glycomics are presented here, based on the use of a panel of immobilized glycan or lectins, and on in silico computational approach. Glycan and lectin arrays are routinely used in combination with other analytical tools to decipher a complex nature of glycan-mediated recognition responsible for signal transduction of a broad range of biological processes. Fundamental aspects of the glycan and lectin array technology are discussed, with the focus on the choice and availability of the biorecognition elements, fabrication protocols, and detection platforms involved. Moreover, practical applications of both technologies especially in the field of clinical diagnostics are provided. The future potential of a complementary in silico array technology to reveal details of the protein-glycan-binding profiles is discussed here.
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Affiliation(s)
- Jaroslav Katrlík
- Department of Glycobiotechnology, Center for Glycomics, Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovakia
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40
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Abstract
Glycan arrays have become a powerful tool for the high-throughput elucidation of interactions of different carbohydrate structures with a wide variety of biological targets, including antibodies, proteins, viruses and cells. This technique is especially suitable for glycomics studies, because arrays present carbohydrate ligands in a manner that mimics interactions at cell-cell interfaces. This review assesses the recent advances involving glycan arrays, including new methods for glycan-array fabrication, new platforms for novel biological information, and new perceptions of glycomics for improving the understanding of disease-related glycobiology. Furthermore, this review attempts to forecast trends in the development of glycan arrays and possible solutions for some remaining challenges to improve this new technology.
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Affiliation(s)
- Chi-Hui Liang
- The Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 115, Taiwan.
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41
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Malickova K, Lakatos PL, Bortlik M, Komarek V, Janatkova I, Lukas M. Anticarbohydrate antibodies as markers of inflammatory bowel disease in a Central European cohort. Eur J Gastroenterol Hepatol 2010; 22:144-150. [PMID: 19927001 DOI: 10.1097/meg.0b013e32832f5c7e] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The study discusses the role of antichitobioside carbohydrate antibody (ACCA), antilaminaribioside carbohydrate antibodies (ALCA), and antimannobioside carbohydrate antibodies (AMCA) in Central European patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS Twohundred and seventy-two serum samples were used - 116 Crohn's disease (CD), 84 ulcerative colitis, and 72 healthy control samples. All samples were evaluated using enzyme-linked immunosorbent assay for the following four anticarbohydrate assays: ACCA, ALCA, AMCA, and anti-Saccharomyces cerevisiae antibodies (gASCA). RESULTS gASCA antibodies showed the highest sensitivity (67%) for a CD diagnosis, followed by AMCA (31%), ACCA (27%), and ALCA (25%). Positivity of at least one of the four assays increased the overall sensitivity of antibody testing in CD up to 85.5%. Mean serum gASCA levels were significantly higher in CD patients who were younger at diagnosis and had a longer disease duration before blood sampling (P<0.001). In nonstricturing, nonpenetrating CD, serum gASCA levels were lower than in patients with stricturing and/or penetrating behavior (P<0.05). The strongest association of gASCA was found with ileocolonic CD and with upper gastrointestinal disease (P<0.001). No association between anticarbohydrate (AMCA, ACCA, and ALCA) antibodies and CD location, behavior, age at onset, and disease duration was found; however, that sample size of some of our subgroups was probably too small to make firm conclusions on associations with all CD phenotypes. None of the assessed anticarbohydrate assays was predictive of colonic CD in patients in whom the distinction between CD and ulcerative colitis is not obvious using routine diagnostic methods. There was no relationship between the presence or concentration of anticarbohydrate antibodies and the inflammation measured by C-reactive protein levels. CONCLUSION The use of a panel of anticarbohydrate antibodies may provide additional help in distinguishing IBD from non-IBD disease patterns. The addition of AMCA, ALCA, and ACCA assays as IBD serology markers improves the overall sensitivity of immunological examinations in IBD; however, anticarbohydrate assays are not helpful for predicting CD behavior.
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Affiliation(s)
- Karin Malickova
- Institute of Clinical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine of Charles University, Budapest, Hungary
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Oyelaran O, McShane LM, Dodd L, Gildersleeve JC. Profiling human serum antibodies with a carbohydrate antigen microarray. J Proteome Res 2009; 8:4301-10. [PMID: 19624168 DOI: 10.1021/pr900515y] [Citation(s) in RCA: 142] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Carbohydrate antigen arrays (glycan arrays) have been recently developed for the high-throughput analysis of carbohydrate macromolecule interactions. When profiling serum, information about experimental variability, interindividual biological variability, and intraindividual temporal variability is critical. In this report, we describe the characterization of a carbohydrate antigen array and assay for profiling human serum. Through optimization of assay conditions and development of a normalization strategy, we obtain highly reproducible results with a within-experiment coefficient of variation (CV) of 10.8% and an overall CV (across multiple batches of slides and days) of 28.5%. We also report antibody profiles for 48 human subjects and evaluate for the first time the effects of age, race, sex, geographic location, and blood type on antibody profiles for a large set of carbohydrate antigens. We found significant dependence on age and blood type of antibody levels for a variety of carbohydrates. Finally, we conducted a longitudinal study with a separate group of 7 serum donors to evaluate the variation in anti-carbohydrate antibody levels within an individual over a period ranging from 3 to 13 weeks and found that, for nearly all antigens on our array, antibody levels are generally stable over this period. The results presented here provide the most comprehensive evaluation of experimental and biological variation reported to date for a glycan array and have significant implications for studies involving human serum profiling.
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Affiliation(s)
- Oyindasola Oyelaran
- Laboratory of Medicinal Chemistry, National Cancer Institute, Frederick, MD 21702, USA
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Kosík O, Auburn RP, Russell S, Stratilová E, Garajová S, Hrmova M, Farkas V. Polysaccharide microarrays for high-throughput screening of transglycosylase activities in plant extracts. Glycoconj J 2009; 27:79-87. [PMID: 19953317 DOI: 10.1007/s10719-009-9271-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2009] [Revised: 09/25/2009] [Accepted: 11/04/2009] [Indexed: 10/20/2022]
Abstract
Polysaccharide transglycosylases catalyze disproportionation of polysaccharide molecules by cleaving glycosidic linkages in polysaccharide chains and transferring their cleaved portions to hydroxyl groups at the non-reducing ends of other polysaccharide or oligosaccharide molecules. In plant cell walls, transglycosylases have a potential to catalyze both cross-linking of polysaccharide molecules and grafting of newly arriving polysaccharide molecules into the cell wall structure during cell growth. Here we describe a polysaccharide microarray in form of a glycochip permitting simultaneous high-throughput monitoring of multiple transglycosylase activities in plant extracts. The glycochip, containing donor polysaccharides printed onto nitrocellulose-coated glass slides, was incubated with crude plant extracts, along with a series of fluorophore-labelled acceptor oligosaccharides. After removing unused labelled oligosaccharides by washing, fluorescence retained on the glycochip as a result of transglycosylase reaction was detected with a standard microarray scanner. The glycochip assay was used to detect transglycosylase activities in crude extracts from nasturtium (Tropaeolum majus) and mouse-ear cress (Arabidopsis thaliana). A number of previously unknown saccharide donor-acceptor pairs active in transglycosylation reactions that lead to the formation of homo- and hetero-glycosidic conjugates, were detected. Our data provide experimental support for the existence of diverse transglycosylase activities in crude plant extracts.
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Affiliation(s)
- Ondrej Kosík
- Institute of Chemistry, Centre for Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 84538, Bratislava, Slovakia
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Sun ZC, Wei Z, Wei KM. Preparation of aldehyde-, amino-, and hydrazide-functionalized polymer particles for direct immobilization of the sugars. J Appl Polym Sci 2009. [DOI: 10.1002/app.30887] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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45
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46
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Zhang J, Pourceau G, Meyer A, Vidal S, Praly JP, Souteyrand E, Vasseur JJ, Morvan F, Chevolot Y. Specific recognition of lectins by oligonucleotide glycoconjugates and sorting on a DNA microarray. Chem Commun (Camb) 2009:6795-7. [PMID: 19885482 DOI: 10.1039/b915132j] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Two glycoconjugates bearing different DNA tags are mixed in solution with lectins; both interact with their specific lectin and the resulting complexes are sorted, according to their DNA sequences, at the surface of micro-reactors bearing the immobilised complementary DNA sequences.
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Affiliation(s)
- Jing Zhang
- INL UMR5270 CNRS Ecole Centrale de Lyon, 36 avenue G. de Collongue, 69134 Ecully cedex, France
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Harris LG, Schofield WCE, Doores KJ, Davis BG, Badyal JPS. Rewritable glycochips. J Am Chem Soc 2009; 131:7755-61. [PMID: 19438244 DOI: 10.1021/ja901294r] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
We describe microarraying of carbohydrates for protein screening using either disulfide bridge or Schiff base imine immobilization chemistries on plasmachemical deposited functional nanolayers. The commonly observed issue of nonspecific background binding of proteins is overcome by spotting carbohydrates through a protein-resistant overlayer yielding spatially localized interaction with a reactive functional underlayer.
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Affiliation(s)
- L G Harris
- Department of Chemistry, Science Laboratories, Durham University, Durham DH1 3LE, UK
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Huflejt ME, Vuskovic M, Vasiliu D, Xu H, Obukhova P, Shilova N, Tuzikov A, Galanina O, Arun B, Lu K, Bovin N. Anti-carbohydrate antibodies of normal sera: findings, surprises and challenges. Mol Immunol 2009; 46:3037-49. [PMID: 19608278 DOI: 10.1016/j.molimm.2009.06.010] [Citation(s) in RCA: 152] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2009] [Accepted: 06/10/2009] [Indexed: 01/01/2023]
Abstract
We have used microchip format glycan array to characterize the individual carbohydrate recognition patterns by antibodies (Ab) in sera of 106 healthy donors. The glycan library included blood group antigens and other most frequent terminal oligosaccharides and their cores of mammalian N- and O-linked glycoproteins and glycolipids, tumor-associated carbohydrate antigens, and common components of bacterial/pathogenic polysaccharides and lipopolysaccharides, totally 205 glycans. The serum Ab interacted with at least 50 normal human glyco-motifs. Apart from expected blood group-, xeno- (heterophil) and infection-related binding activities, we observed a number of new and unexpected features. The surprising, relatively high antibody binding was found to the blood group P(1) and P(k) trisaccharides and H(type 2) trisaccharide. Novel and very high binding activities have been observed towards Galbeta1-3GlcNAc (Le(C)) related glycans, especially 3'-O-Su-Le(C), and towards 4'-O-sulfated lactosamine. Relatively high and uniform Ab binding to GalNAcalpha1-3Gal disaccharide demonstrated absence of correlation with fucosylated blood group A GalNAcalpha1-3(Fucalpha1-2)Gal antigen-similarly to well known relationship between Galalpha1-3Gal and true, fucosylated blood group B Galalpha1-3(Fucalpha1-2)Gal antigen. The binding intensity to Galalpha1-3Galbeta1-4GlcNAc xenoantigen was shown to be rather modest. Absence or very low Ab binding was found against oligosialic acid, sialooligosaccharides except SiaT(n), type 2 backbone glycans such as Le(y), and biantennary N-chain as well as its truncated forms, i.e. without terminal Sia, SiaGal, and SiaGalGlcNAc motifs. We have also found that Ab are capable of recognizing the short inner core typical for glycolipids (-Galbeta1-4Glc) and glycoproteins (-GalNAcalpha) as a fragment of bigger glycans.
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Affiliation(s)
- Margaret E Huflejt
- New York University School of Medicine, Dept. of Cardiothoracic Surgery, New York, NY 10016, USA
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Freedman MS, Laks J, Dotan N, Altstock RT, Dukler A, Sindic CJM. Anti-alpha-glucose-based glycan IgM antibodies predict relapse activity in multiple sclerosis after the first neurological event. Mult Scler 2009; 15:422-30. [PMID: 19324980 PMCID: PMC2850589 DOI: 10.1177/1352458508101944] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background There is no specific serum-based biomarker for the diagnosis or prognosis of
relapsing-remitting multiple sclerosis (RRMS). Objective We investigated whether levels of IgM antibodies to
Glc(α1,4)Glc(α) (GAGA4) or to a panel of four
glucose-based glycans could differentiate MS from other neurological
diseases (OND) or predict risk of early relapse following first presentation
(FP) of RRMS. Methods Retrospective analysis of 440 sera samples of three cohorts: A) FP-RRMS (n =
44), OND (n = 44); B) FP-RRMS (n = 167), OND (n = 85); and C) FP (n = 100).
Anti-GAGA4 IgM levels were measured by enzyme immunoassay in cohort-A and
cohort-B. Cohort-C IgM antibodies to glucosebased glycan panel were measured
by immunofluorescence. Results FP-RRMS had higher levels of anti-GAGA4 IgM than OND patients (cohort-A, P =
0.01; cohort-B, P = 0.0001). Sensitivity and specificity were 27% and 97%
for cohort-A; and 26% and 90% for cohort-B, respectively. In cohort-C, 58
patients experienced early relapse (<24 months), 31 had late
relapse (≥24 months), and 11 did not experience second attack
during follow-up. Kaplan– Meier curves demonstrated decrease in
time to next relapse for patients positive for the antibody panel (P = 0.02,
log rank). Conclusions Serum anti-GAGA4 IgM discerns FP-RRMS patients from OND patients. Higher
levels of serum anti-α-glucose IgM in FP patients predict
imminent early relapse.
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Affiliation(s)
- M S Freedman
- University of Ottawa, The Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6.
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Geetha M, Annamma KI, Mathai J, Appukuttan PS. Normal Human Plasma Anti-β-Glucoside Antibody Has Markedly Elevated IgA Content and Binds Fungal and Yeast Polysaccharides. Immunol Invest 2009; 36:73-83. [PMID: 17190651 DOI: 10.1080/08820130600745737] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Normal human plasma antibody that recognizes beta-linked glucoside moiety was purified by affinity chromatography on cellulose. The anti-beta-glucoside antibody had three times higher IgA to IgG ratio and substantially higher polymeric IgA content than total serum immunoglobulins. Cellobiose and other beta-glucosides were best inhibitors of its binding to polystyrene microwell-coated polysaccharides. In synthetic glycoproteins made by conjugating disaccharides to hemoglobin or bovine serum albumin, cellobiose, unlike lactose or maltose, was sugar-specifically recognized by the antibody. It also recognized polystyrene well-coated beta1-->3 linked glycans of Saccharomyces cerevisiae, Candida albicans and of barley in decreasing order of affinity. Its sugar-binding site could thus accommodate beta-glucoside with or without substitution at C4 and C3. High IgA content along with the capacity to bind common microbial and dietary antigens pointed to the immune inflammatory potential of the antibody.
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Affiliation(s)
- M Geetha
- Department of Biochemistry, Sree Chitra Thirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India
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