Article
Chemistry, Multidisciplinary
Vidya S. S. Shivatare, Po-Kai Chuang, Tzu-Hao Tseng, Yi-Fang Zeng, Han-Wen Huang, Gannedi Veeranjaneyulu, Han-Chung Wu, Chi-Huey Wong
Summary: A comprehensive structure-activity relationship study on antibody Fc-glycosylation was conducted using a chimeric anti-SSEA4 antibody chMC813-70 as a model. The α-2,6 sialylated biantennary complex type glycan was identified as the optimal Fc-glycan, which significantly enhanced antibody effector functions, including binding to different Fc receptors and ADCC.
CHEMICAL COMMUNICATIONS
(2023)
Review
Biotechnology & Applied Microbiology
Mikel Garcia-Alija, Berre van Moer, Diego E. Sastre, Tala Azzam, Jonathan J. Du, Beatriz Trastoy, Nico Callewaert, Eric J. Sundberg, Marcelo E. Guerin
Summary: Antibody-based drugs, including IgG monoclonal antibodies, are widely used for treating cancer, autoimmune, and infectious diseases. Different glycoforms attached to antibodies can affect their efficacy, stability, and effector functions. Therefore, various antibody engineering strategies have been developed to produce antibodies with tailored glycoforms.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Multidisciplinary Sciences
Helena Deris, Domagoj Kifer, Ana Cindric, Tea Petrovic, Ana Cvetko, Irena Trbojevic-Akmacic, Ivana Kolcic, Ozren Polasek, Louise Newson, Tim Spector, Cristina Menni, Gordan Lauc
Summary: Gonadal hormones affect the glycosylation of IgG, and the more proinflammatory IgG glycome composition might be one of the molecular mechanisms behind the increased proinflammatory phenotype in perimenopause.
Review
Immunology
Alessandra Zarantonello, Margot Revel, Anne Grunenwald, Lubka T. Roumenina
Summary: This article introduces the central effector molecule of the complement system, C3, and its various forms and fragments. It discusses the role of C3 in diseases and the process of C3 activation. The article also provides a detailed description of the interactions between C3a and opsonins with receptors, as well as the molecular architecture and functions of the receptors.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Yannic C. Bartsch, Deniz Cizmeci, Jaewon Kang, Tomer Zohar, Sivakumar Periasamy, Nickita Mehta, Jeroen Tolboom, Leslie Van der Fits, Jerry Sadoff, Christy Comeaux, Benoit Callendret, Alexander Bukreyev, Douglas A. Lauffenburger, Arangassery Rosemary Bastian, Galit Alter
Summary: RSV infection is a major cause of severe respiratory tract infection and death in infants and the elderly. This study found that protection against RSV infection is linked to opsonophagocytic functions driven by IgA and differentially glycosylated RSV-specific IgG profiles, indicating the importance of functional humoral immune response in preventing RSV.
Review
Immunology
Kristina Zlatina, Sebastian P. Galuska
Summary: This review discusses the impact of glycosylation on the function of antibodies, specifically Ig, and how changes in glycosylation affect their functionality. It also explores the functionality of IgG glycosylation in different physiological states, such as aging, lactation, and pathophysiological processes. Additionally, it points out the current knowledge about Ig glycosylation in farm animals and the potential contributions of new advancements in vaccination to animal welfare.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Michaela Seeling, Matthias Poehnl, Sibel Kara, Nathalie Horstmann, Carolina Riemer, Miriam Woehner, Chunguang Liang, Christin Brueckner, Patrick Eiring, Anja Werner, Markus Biburger, Leon Altmann, Martin Schneider, Lukas Amon, Christian H. K. Lehmann, Sooyeon Lee, Meik Kunz, Diana Dudziak, Georg Schett, Tobias Baeuerle, Anja Lux, Jan Tuckermann, Timo Voegtle, Bernhardt Nieswandt, Markus Sauer, Rainer A. Boeckmann, Falk Nimmerjahn
Summary: Immunoglobulin G (IgG) antibodies are major drivers of inflammation, but in pooled serum IgG (IVIg), they have immunomodulatory and anti-inflammatory activity. The mechanism behind this activity is unclear. The study found that IVIg sialylation inhibited joint inflammation in rheumatoid arthritis models, and the inhibition of osteoclastogenesis was independent of sialic acid. Instead, IVIg-dependent inhibition of osteoclastogenesis required the presence of receptors Dectin-1 or FcgRIIb. This research reveals a novel role of Dectin-1 as a co-inhibitory checkpoint for IgG-dependent inhibition of osteoclastogenesis.
Article
Biotechnology & Applied Microbiology
Qiong Wang, Tiexin Wang, Roushu Zhang, Shuang Yang, Kevin S. McFarland, Cheng-Yu Chung, Hongpeng Jia, Lai-Xi Wang, John F. Cipollo, Michael J. Betenbaugh
Summary: This study investigates the impact of N-glycan pattern on the quality and function of IgG antibodies, and explores the methods of glycoengineering and protein engineering to modify these effects. The results show that glycoengineering and protein engineering can alter the glycan composition and structure of antibodies, thereby affecting their effector functions such as cytotoxicity and cellular adhesion. Additionally, the study reveals that different glycan compositions and structures have different effects on the cytotoxicity and cellular adhesion of antibodies.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Review
Immunology
Andrea Cottignies-Calamarte, Daniela Tudor, Morgane Bomsel
Summary: Recent advances in therapeutic antibodies have greatly improved the treatment of drug-resistant cancers and autoimmune diseases. Fc-bioengineering has been widely used to enhance the efficacy and convenience of therapeutic antibodies, although IgG remains the most commercially available. However, interest in IgA is growing due to its enhanced binding to Fc receptors and potential synergistic effects with IgG.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Iwona Wojcik, David E. Schmidt, Lisa A. de Neef, Minke A. E. Rab, Bob Meek, Okke de Weerdt, Manfred Wuhrer, C. Ellen van der Schoot, Jaap J. Zwaginga, Masja de Haas, David Falck, Gestur Vidarsson
Summary: The spleen plays a crucial role in adaptive immune responses to viral infections and alloantigens by hosting a variety of immune cell populations. Splenectomy leads to an increase in IgG-Fc fucosylation, suggesting that the spleen may play a role in generating afucosylated IgG responses. Unexpectedly, ITP patients show a decrease in total IgG-Fc fucosylation compared to healthy controls, pointing to a potential role of the spleen in regulating afucosylated IgG responses.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Peter G. E. Kennedy, Michael Graner, Tiffany Pointon, Xiaomeng Li, Kayo Tanimoto, Kathryn Dennison, Gina Im, Anthony Fringuello, Wenbo Zhou, Arin Graner, Stefan Sillau, Timothy Vollmer, Xiaoli Yu
Summary: The study found that levels of sialylated IgG were lower in the cerebrospinal fluid of multiple sclerosis patients, while levels of galactosylated IgG were higher in the serum. These unique IgG glycosylation profiles may play a significant role in the pathogenesis of multiple sclerosis.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Bala Reddy Bheemareddy, Prakash Narayana Reddy, Kranthi Vemparala, Vijaya R. Dirisala
Summary: This study developed a simple and cost-effective approach to enhance antibody-dependent cellular cytotoxicity (ADCC) activity in anti-CD20 monoclonal antibodies by increasing afucosylation. The findings suggest that modulating afucosylation using osmolality can significantly improve the efficacy of immunotherapy.
JOURNAL OF GENETIC ENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Immunology
Dominic Paquin-Proulx, Bronwyn M. Gunn, Aljawharah Alrubayyi, Danielle V. Clark, Matthew Creegan, Dohoon Kim, Hannah Kibuuka, Monica Millard, Salim Wakabi, Leigh Anne Eller, Nelson L. Michael, Randal J. Schoepp, Matthew J. Hepburn, Lisa E. Hensley, Merlin L. Robb, Galit Alter, Michael A. Eller
Summary: This study found that in survivors of EBOV infection, antibodies mediating different effector functions and persistent inflammation may contribute to the development of long-term sequelae, particularly hearing loss.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hannah Bauer-Smith, Abigail S. L. Sudol, Stephen A. Beers, Max Crispin
Summary: Antibodies play an important role in immune recruitment or clearance of immune complexes through their interaction with cellular Fc receptors. The presence of endogenous immunoglobulin can affect the engagement of cellular receptors. This review examines the factors controlling serum IgG levels and discusses how endogenous IgG influences the functional activation thresholds of low- and high-affinity Fc receptors. Furthermore, it explores the potential of antibody engineering and pharmacological control to overcome physiological limitations and enhance antibody therapeutics.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2023)
Article
Immunology
William D. D. Tolbert, Neelakshi Gohain, Paul G. G. Kremer, Andrew P. P. Hederman, Dung N. N. Nguyen, Verna Van, Rebekah Sherburn, George K. K. Lewis, Andres Finzi, Justin Pollara, Margaret E. E. Ackerman, Adam W. W. Barb, Marzena Pazgier
Summary: Fc mediated effector functions of antibodies are crucial in immunotherapies and vaccine efficacy. The Ile/Val(158) polymorphism in Mm Fc gamma RIII and glycan composition variations affect the affinity of allelic variants, providing important insights for nonhuman primate studies and human effector cell studies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Sander J. van Tilburg, Bart C. Jacobs, Pleuni Ooijevaar-de Heer, Willem-Jan R. Fokkink, Ruth Huizinga, Gestur Vidarsson, Theo Rispens
Summary: This study developed novel ELISAs to specifically monitor the pharmacokinetics of IVIg, utilizing polymorphic determinants G1m(a), G1m(x), and G1m(f). The assays can discriminate between endogenous IgG and therapeutic polyclonal IgG, providing insights into the variability of IVIg pharmacokinetics.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Tamas Pongracz, Gestur Vidarsson, Manfred Wuhrer
Summary: Antibody glycosylation plays a critical role in COVID-19 infections, affecting the effectiveness and safety of immune responses. This review summarizes recent research on antibody glycosylation in COVID-19, evaluating research methods and the dynamics, effector functions, clinical utility, and regulation of glycosylation. Future research could explore other antibody classes, non-canonical antibody receptors, and the regulation of antibody glycosylation.
GLYCOCONJUGATE JOURNAL
(2022)
Article
Cell Biology
Thijs L. J. van Osch, Juulke Steuten, Jan Nouta, Carolien A. M. Koeleman, Arthur E. H. Bentlage, Sebastiaan Heidt, Arend Mulder, Jan Voorberg, S. Marieke van Ham, Manfred Wuhrer, Anja Ten Brinke, Gestur Vidarsson
Summary: Immune-mediated platelet refractoriness (PR) is a significant issue in platelet transfusion, mainly caused by alloantibodies against human leukocyte antigens (HLA). Variations in HLA-specific IgG responses have been observed between alloimmunized patients. This study found that different Fc glycosylation patterns did not affect phagocytosis of opsonized platelets by monocyte-derived human macrophages.
Article
Multidisciplinary Sciences
Maximilian Brinkhaus, Erwin Pannecoucke, Elvera J. van der Kooi, Arthur E. H. Bentlage, Ninotska I. L. Derksen, Julie Andries, Bianca Balbino, Magdalena Sips, Peter Ulrichts, Peter Verheesen, Hans de Haard, Theo Rispens, Savvas N. Savvides, Gestur Vidarsson
Summary: Disrupting the association between the Immunoglobulin G constant fragment (Fc) and the neonatal Fc receptor (FcRn) by engineered antibodies is a promising strategy to reduce autoantibody levels in autoimmune diseases. Here authors show that the variable fragment (Fab) of immunoglobulins could disturb the Fc-FcRn interaction, therefore the therapeutic effect of Fc-only fragments might surpass that of Fc-engineered antibodies with enhanced binding to FcRn.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Julie Van Coillie, Morten A. Schulz, Arthur E. H. Bentlage, Noortje de Haan, Zilu Ye, Dionne M. Geerdes, Wim J. E. van Esch, Lise Hafkenscheid, Rebecca L. Miller, Yoshiki Narimatsu, Sergey Y. Vakhrushev, Zhang Yang, Gestur Vidarsson, Henrik Clausen
Summary: Immunoglobulins G and their Fc gamma receptors play crucial roles in the immune system, and the N-glycan in IgG1 affects their interaction. This study genetically engineered N-glycan structures to investigate the role of N-glycosylation in IgG1:Fc gamma RIIIa binding. The findings demonstrate that afucosylated IgG1 binds with the highest affinity to oligomannose Fc gamma RIIIa.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Christoph Gstottner, Alexander Knaupp, Gestur Vidarsson, Dietmar Reusch, Tilman Schlothauer, Manfred Wuhrer, Elena Dominguez-Vega
Summary: The impact of antibody glycoforms on Fc gamma RIIa activation and immune responses was investigated using an affinity capillary electrophoresis-mass spectrometry approach. The results showed clear differences in binding between different glycoforms of antibodies, and the assay was also evaluated for different variants of the Fc gamma RIIa receptor. This method provides a fast and efficient way to establish the structure-function relationships of different antibody species.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Mikhail Volkov, Maximilian Brinkhaus, Karin A. van Schie, Albert Bondt, Theresa Kissel, Elvera J. van der Kooi, Arthur E. H. Bentlage, Carolien A. M. Koeleman, Steven W. de Taeye, Ninotska I. Derksen, Radboud J. E. M. Dolhain, Ute Braig-Scherer, Tom W. J. Huizinga, Manfred Wuhrer, Rene E. M. Toes, Gestur Vidarsson, Diane van der Woude
Summary: Glycosylation in the Fc and Fab regions of antibodies can affect their function and binding. Fab glycans negatively impact the interaction between IgG and hFcRn and reduce the transport of IgG across the placenta. Fab-glycosylated antibodies are frequently associated with autoimmune and malignant disorders and may have potential harmful effects.
JOURNAL OF IMMUNOLOGY
(2023)
Correction
Immunology
Angela I. Schriek, Marlies M. van Haaren, Meliawati Poniman, Gillian Dekkers, Arthur E. H. Bentlage, Marloes Grobben, Gestur Vidarsson, Rogier W. Sanders, Theo Verrips, Teunis B. H. Geijtenbeek, Raimond Heukers, Neeltje A. Kootstra, Steven W. de Taeye, Marit J. van Gils
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Nienke Oskam, Timon Damelang, Marij Streutker, Pleuni Ooijevaar-de Heer, Jan Nouta, Carolien Koeleman, Julie Van Coillie, Manfred Wuhrer, Gestur Vidarsson, Theo Rispens
Summary: Of the four human IgG subclasses, IgG4 is the least inflammatory due to poor activation of the complement system. However, in certain diseases, IgG4 antibodies have been linked to complement consumption and deposition. This study investigated the ability of IgG4 to activate complement and found that it can only do so at high antigen and antibody concentrations via the classical pathway. Glycosylation and Fab arm exchange influenced complement activation, with reduced Fc galactosylation diminishing activation. These findings suggest that IgG4-mediated complement activation in pathology is possible but unlikely.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Julie Van Coillie, Tamas Pongracz, Johann Rahmoeller, Hung-Jen Chen, Chiara Elisabeth Geyer, Lonneke A. van Vught, Jana Sophia Buhre, Tonci Sustic, Thijs Luc Junior van Osch, Maurice Steenhuis, Willianne Hoepel, Wenjun Wang, Anne Sophie Lixenfeld, Jan Nouta, Sofie Keijzer, Federica Linty, Remco Visser, Mads Delbo Larsen, Emily Lara Martin, Inga Kuensting, Selina Lehrian, Vera von Kopylow, Carsten Kern, Hanna Bele Lunding, Menno de Winther, Niels van Mourik, Theo Rispens, Tobias Graf, Marleen Adriana Slim, Rene Peter Minnaar, Marije Kristianne Bomers, Jonne Jochum Sikkens, Alexander P. J. Vlaar, C. Ellen van der Schoot, Jeroen den Dunnen, Manfred Wuhrer, Marc Ehlers, Gestur Vidarsson
Summary: The BNT162b2 mRNA vaccine induces transient afucosylated anti-S IgG1 responses in naive individuals, but not in antigen-experienced ones. Further studies are needed to determine the clinical context in which potent afucosylated responses would be preferred.
Article
Immunology
Esther C. W. de Boer, Astrid J. F. Thielen, Jeroen D. Langereis, Angela Kamp, Mieke C. Brouwer, Nienke Oskam, Marlieke L. Jongsma, April J. Baral, Robbert M. Spaapen, Sacha Zeerleder, Gestur Vidarsson, Theo Rispens, Diana Wouters, Richard B. Pouw, Ilse Jongerius
Summary: This study investigated the role of the alternative pathway (AP) in antibody-mediated complement activation. The results show that the AP amplification loop is redundant when efficient classical pathway (CP) activation takes place. The role of the AP may become significant when CP activation is insufficient, but this depends on antibody levels and subclasses.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2023)
Review
Immunology
Falk Nimmerjahn, Gestur Vidarsson, Mark S. Cragg
Summary: Humoral immune responses generate polyclonal antibodies with varied isotypes, epitope specificity, and affinity. Posttranslational modifications in antibody variable and constant domains can modify antigen specificity and antibody Fc-dependent functions. Understanding the impact of these modifications on antibody function is still limited, but it has implications for therapeutic antibody development. This Review provides insights into how IgG subclass and posttranslational modifications influence antibody activity and discusses their implications in designing therapeutic antibodies for different clinical indications.
Article
Multidisciplinary Sciences
Julie Van Coillie, Tamas Pongracz, Tonci Sustic, Wenjun Wang, Jan Nouta, Mathieu Le Gars, Sofie Keijzer, Federica Linty, Olvi Cristianawati, Jim B. D. Keijser, Remco Visser, Lonneke A. van Vught, Marleen A. Slim, Niels van Mourik, Merel J. Smit, Adam Sander, David E. Schmidt, Maurice Steenhuis, Theo Rispens, Morten A. Nielsen, Benjamin G. Mordmueller, Alexander P. J. Vlaar, C. Ellen van der Schoot, Ramon Roozendaal, Manfred Wuhrer, Gestur Vidarsson
Summary: In this study, the glycosylation profiles of anti-S IgG1 Fc in response to mRNA, adenoviral, and protein-based COVID-19 vaccines were compared using mass spectrometry (MS). The results showed variations in the glycosylation patterns between different vaccine platforms and individuals, but overall, vaccine-induced anti-S IgG glycosylation was dynamic with marked overlaps.
Article
Immunology
Kelly A. Dingess, Max Hoek, Danique M. H. van Rijswijk, Sem Tamara, Maurits A. den Boer, Tim Veth, Mirjam J. A. Damen, Arjan Barendregt, Michelle Romijn, Hannah G. Juncker, Britt J. van Keulen, Gestur Vidarsson, Johannes B. van Goudoever, Albert Bondt, Albert J. R. Heck
Summary: The most abundant immunoglobulin in the human body is IgA and it is found in high concentrations in mucosal lining and biofluids like milk. The structure and clonal repertoire of IgA1-containing molecular assemblies were analyzed using mass spectrometry-based approach in serum and milk from three donors. The results showed that serum IgA1 consists of two distinct structural populations, monomeric IgA1 and dimeric J-chain coupled IgA1, while IgA1 in milk is present only as secretory IgA (SIgA) with various assemblies. The IgA1-Fab repertoires in serum and milk were also found to be different.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Immunology
Nienke Oskam, Pleuni Ooijevaar-de Heer, Ninotska I. L. Derksen, Simone Kruithof, Steven W. de Taeye, Gestur Vidarsson, Sanne Reijm, Theresa Kissel, Rene E. M. Toes, Theo Rispens
Summary: This study systematically investigated human IgM-mediated complement activation and found that hexameric IgM outperformed pentameric IgM and IgG1 in complement activation at low antigen densities, highlighting the importance of IgM in immunity.
JOURNAL OF IMMUNOLOGY
(2022)