Article
Immunology
Patricia S. Grace, Sepideh Dolatshahi, Lenette L. Lu, Adam Cain, Fabrizio Palmieri, Linda Petrone, Sarah M. Fortune, Tom H. M. Ottenhoff, Douglas A. Lauffenburger, Delia Goletti, Simone A. Joosten, Galit Alter
Summary: This study compared the serum antibody features at different stages of tuberculosis and identified two novel TB-specific antibody changes that track with the resolution of tuberculosis, providing key insights for guiding TB therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Evgenij Fiskin, Caleb A. Lareau, Leif S. Ludwig, Gokcen Eraslan, Feimei Liu, Aaron M. Ring, Ramnik J. Xavier, Aviv Regev
Summary: The study introduces a novel method called PHAGE-ATAC for simultaneous single-cell measurements of protein levels and chromatin accessibility profiles, using mitochondrial DNA-based clonal tracing. PHAGE-ATAC is utilized for multimodal analysis in primary human immune cells, sample multiplexing, intracellular protein analysis, and detection of SARS-CoV-2 spike protein. Additionally, a synthetic high-complexity phage library is constructed for selection of antigen-specific nanobodies, enabling protein detection, cell characterization, and screening with single-cell genomics.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hong-Yang Chuang, Chiu-Chen Huang, Ting-Chun Hung, Lin -Ya Huang, Chih-Wei Chiu, Kuo-Ching Chu, Jung-Yu Liao, Tsai-Hong You, Chung-Yi Wu, Ping Chao, Sachin S. Shivatare, Yi-Fang Zeng, Charng-Sheng Tsai, Nan-Horng Lin, Chung-Yi Wu
Summary: Chemoenzymatic remodeled monoclonal antibodies with defined glycan structure at the Fc domain show improved biological activities and safety profiles; immobilizing enzymes on magnetic beads efficiently generates homogeneous antibody glycoforms without additional purification steps.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Analytical
Mathieu Lamarre, Thomas Tremblay, Marc-Antoine Bansept, Karine Robitaille, Vincent Fradet, Denis Giguere, Denis Boudreau
Summary: In this study, a sensor immobilized with Tn antigen on a surface coated with polydopamine/polyethylene oxide showed high reliability and sensitivity in prostate cancer diagnostics. Detection limits of anti-Tn antibodies were validated in different concentration ranges and successfully used to discriminate blood serum samples from prostate cancer patients and cancer-free individuals.
Review
Medicine, General & Internal
Maria Arguello Marina, Montserrat Lopez Rubio, Lucia Castilla Garcia
Summary: Autoimmune haemolytic anaemias (AIHA) are acquired haematological disorders caused by autoantibodies against erythrocyte antigens, and they can be classified into primary and secondary according to the aetiology, and into warm antibody AIHA (w-AIHA) and cold antibody AIHA (c-AIHA) based on the type of antibody and reaction temperature. Glucocorticoid therapy is the main treatment for w-AIHA, and recent studies have shown that the early addition of rituximab has good results. Primary c-AIHA is mainly treated with rituximab, alone or in combination with chemotherapy. New drugs such as Syk inhibitors, anti-FcRn Ig, and complement inhibitors are being developed and will expand the therapeutic arsenal, especially for refractory or relapsed cases.
Article
Biochemistry & Molecular Biology
Thibault J. Harmand, Novalia Pishesha, Fabian B. H. Rehm, Weiyi Ma, William B. Pinney, Yushu J. Xie, Hidde L. Ploegh
Summary: RBCs can serve as carriers for drugs and proteins in the vascular system, with the potential to induce immune tolerance to foreign components. A new method allows direct conjugation of peptides and proteins onto RBCs with retention of their properties and potential for targeting cancer cells. This approach provides an appealing alternative to current RBC engineering methods.
ACS CHEMICAL BIOLOGY
(2021)
Review
Immunology
Gabriel Osborn, Chara Stavraka, Rebecca Adams, Ahmad Sayasneh, Sharmistha Ghosh, Ana Montes, Katie E. Lacy, Rebecca Kristeleit, James Spicer, Debra H. Josephs, James N. Arnold, Sophia N. Karagiannis
Summary: This review discusses the role of tumor-associated macrophages (TAMs) in the ovarian cancer tumor microenvironment (TME) and the emerging strategies that target the contributions of these cells in tumor progression through the rational design of monoclonal antibodies (mAbs).
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2022)
Article
Immunology
Ebene R. Haycroft, Timon Damelang, Ester Lopez, Mark A. Rodgers, Bruce D. Wines, Mark Hogarth, Cassaundra L. Ameel, Stephen J. Kent, Charles A. Scanga, Shelby L. O'Connor, Amy W. Chung
Summary: This study used a macaque model of tuberculosis and HIV co-infection to investigate the humoral responses. They found that antibody responses to tuberculosis were impaired during HIV co-infection. The study suggests that humoral immunity and antibody glycosylation may play a role in the control and progression of tuberculosis.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Yuanjun Wu, Yong Wu, Yanli Ji, Jiajie Liang, Ziyi He, Yanhui Liu, Li Tang, Ganping Guo
Summary: This report describes a case of drug-induced immune haemolytic anaemia caused by cefoperazone-dependent antibodies, leading to fatal haemolytic anaemia and renal function impairment in a 59-year-old man. The presence of cefoperazone-dependent IgM and IgG antibodies, as well as positive results for anti-IgG and anti-C3d direct antiglobulin test, suggests that cefoperazone can activate complement and promote haemolysis through immunocomplex formation and complement activation. Discontinuation of cefoperazone treatment resulted in negative DAT results, indicating resolution of the haemolytic anaemia.
FRONTIERS IN MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Chang Gao, Qingyan Chen, Xinxin Hao, Qiushi Wang
Summary: This review examines the importance of establishing immune balance between the mother and fetus during gestation, with a focus on the role of the placenta in immune tolerance. It explores the immunomodulation of antibody glycosylation during placental transfer and its impact on fetal health. The review also investigates factors influencing antibody transfer efficiency and discusses the effects of glycosylation patterns on antibody functionality.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Medicine, General & Internal
Aditya Samitinjay, Arjun Ramavath, Sai Charan Kulakarni, Rakesh Biswas
Summary: Autoimmune disorders can be common manifestations of immunodeficiency syndromes. This case report highlights the challenges faced by a teenage woman with a history of recurring sinopulmonary tract infections, presenting with anemia, jaundice, fatigue, and growth retardation. Feasible solutions to address these challenges are also proposed.
Article
Chemistry, Analytical
Cuiyan Cao, Long Yu, Xiuli Zhang, Xuefang Dong, Jingli Yuan, Xinmiao Liang
Summary: The calibration strategy using a library of glycopeptide standards significantly improved the accuracy and precision of Fc-glycosylation analysis of mAbs, especially when coupled with HILIC separation. Transferability of the calibrated quantitation across different instruments and laboratories was also enhanced, indicating its utility for Fc-glycosylation analysis of IgG1-type mAbs with multiple glycosylation sites.
ANALYTICA CHIMICA ACTA
(2021)
Review
Medicine, General & Internal
Anthony Pak-yin Liu, Daniel K. L. Cheuk
Summary: The study compared the use of rituximab and glucocorticoids versus glucocorticoids alone in treating newly diagnosed warm AIHA patients, suggesting that combination therapy may increase the rate of complete hematologic response.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
Article
Oncology
Sayed Shahabuddin Hoseini, Mallika Vadlamudi, Madelyn Espinosa-Cotton, Hoa Tran, Yi Feng, Hong-Fen Guo, Hong Xu, Irene Cheung, Nai-Kong Cheung
Summary: This study presented data on three bispecific antibodies against the CD33 IgV and IgC domains, showing their effect on AML cell lines through in vitro binding and cytotoxicity assays. The findings support further clinical development of these BsAbs for potential first-in-human phase I clinical trial.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemical Research Methods
Baubek Spanov, Bas Baartmans, Oladapo Olaleye, Simone Nicolardi, Natalia Govorukhina, Manfred Wuhrer, Nico C. van de Merbel, Rainer Bischoff
Summary: We have developed a method using pH gradient cation-exchange chromatography to reveal the charge heterogeneity of stressed trastuzumab at the subunit level. This approach can be used for charge variant analysis of therapeutic antibodies with two or more modification sites in the Fab region.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Steffen Lippold, Michaela Hook, Christian Spick, Alexander Knaupp, Kevin Whang, Fabian Ruperti, Lance Cadang, Nisana Andersen, Annette Vogt, Michael Grote, Dietmar Reusch, Markus Haberger, Feng Yang, Tilman Schlothauer
Summary: T-cell engaging bispecific antibodies (TCBs) targeting CD3 and tumor-specific antigens show great promise as therapeutics. In this study, we developed a novel method using functional CD3 target affinity chromatography (AC) coupled with online mass spectrometry (MS) to separate and identify critical modified proteoforms of TCBs. This method enables the functional distinction of important modifications and the evaluation of product-related variants, streamlining the integration of functional and structural characterizations of therapeutic CD3 targeting TCBs.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jing Zhang, Gerard van Der Zon, Jin Ma, Hailiang Mei, Birol Cabukusta, Cedrick C. Agaser, Katarina Madunic, Manfred Wuhrer, Tao Zhang, Peter ten Dijke
Summary: Epithelial-mesenchymal transition (EMT) is important in cancer cell metastasis. The abundance of glycosphingolipids (GSLs), specifically ganglioside subtypes, decreases during TGF-beta-induced EMT. Inhibition of UDP-glucose ceramide glucosyltransferase (UGCG), the enzyme responsible for GSL biosynthesis, promotes TGF-beta signaling and EMT. ST3GAL5-synthesized a-series gangliosides inhibit TGF-beta signaling and EMT in lung cancer cells.
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)
Article
Biochemistry & Molecular Biology
Di Wang, Valeriia Kuzyk, Katarina Madunic, Tao Zhang, Oleg A. Mayboroda, Manfred Wuhrer, Guinevere S. M. Lageveen-Kammeijer
Summary: Colorectal cancer (CRC) is a common and deadly type of cancer. Studying the N-glycosylation of CRC cell lines can help identify potential therapeutic and diagnostic targets. The study found a diverse range of N-glycans among the examined CRC cell lines and discovered similarities between different platforms used for analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Agriculture, Multidisciplinary
Rui-Rui Guo, Guinevere S. M. Lageveen-Kammeijer, Wenjun Wang, Hans Dalebout, Wangang Zhang, Manfred Wuhrer, Li Liu, Bram Heijs, Josef Voglmeir
Summary: Severe allergic reactions to certain types of meat have been observed in areas with ticks, due to an immune response to a carbohydrate antigen called alpha-Gal. The presence and distribution of alpha-Gal-modified N-glycans in different meats were studied, and it was found that these modified glycans were abundant in beef, mutton, and pork, mainly present in fibroconnective tissue. This study contributes to a better understanding of the glycosylation biology of meat and provides guidance for processed meat products.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemical Research Methods
Alan B. Moran, Elena Dominguez-Vega, Manfred Wuhrer, Guinevere S. M. Lageveen-Kammeijer
Summary: Intact protein analysis by mass spectrometry is important for assessing post-translational modifications and biotransformation. The lack of consensus on the best practice for data processing and unfit data processing tools make analysis of intact proteins laborious. This study investigated a software-assisted workflow for streamlined intact protein data processing and quantification. The results showed comparable quantification to manually performed quantification, demonstrating the efficiency of the presented workflow.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Immunology
Paulina Kaplonek, Deniz Cizmeci, Gaurav Kwatra, Alane Izu, Jessica Shih-Lu Lee, Harry L. Bertera, Stephanie Fischinger, Colin Mann, Fatima Amanat, Wenjun Wang, Anthonet L. Koen, Lee Fairlie, Clare L. Cutland, Khatija Ahmed, Keertan Dheda, Shaun L. Barnabas, Qasim Ebrahim Bhorat, Carmen Briner, Florian Krammer, Erica Ollman Saphire, Sarah C. Gilbert, Teresa Lambe, Andrew J. Pollard, Marta Nunes, Manfred Wuhrer, Douglas A. Lauffenburger, Shabir A. Madhi, Galit Alter
Summary: Despite the success of COVID-19 vaccines, breakthrough infections can occur due to SARS-CoV-2 variants. The immune mediators of protection in humans are still unknown. A study on ChAdOx1 nCoV-19 (AZD1222) vaccine recipients in South Africa found different Fc-receptor-binding antibodies among different groups. Individuals who resisted COVID-19 exclusively had Fc gamma R3B-binding antibodies, while those who experienced breakthrough had enhanced IgA and IgG3 with enriched Fc gamma R2B binding. Antibodies unable to bind to Fc gamma R3B led to immune complex clearance and inflammation. The differential antibody binding to Fc gamma R3B was associated with Fc-glycosylation differences in SARS-CoV-2-specific antibodies.
Article
Biochemical Research Methods
Florent Clerc, Karli R. Reiding, Noortje de Haan, Carolien A. M. Koeleman, Agnes L. Hipgrave Ederveen, Natalia Manetti, Viktoria Dotz, Vito Annese, Manfred Wuhrer
Summary: This study investigates the associations of immunoglobulin A1 and A2 glycosylation with inflammatory bowel diseases (IBD). Differences in IgA O- and N-glycosylation between patient groups were found to be associated with the diseases, and a statistical model was constructed to predict the disease group of the patients. These findings contribute to the development of noninvasive biomarkers for IBD and improvement in patient care.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Immunology
Zoltan Szittner, Arthur E. H. Bentlage, A. Robin Temming, David E. Schmidt, Remco Visser, Suzanne Lissenberg-Thunnissen, Juk Yee Mok, Wim J. E. van Esch, Myrthe E. Sonneveld, Erik L. de Graaf, Manfred Wuhrer, Leendert Porcelijn, Masja de Haas, C. Ellen van der Schoot, Gestur Vidarsson
Summary: The core fucosylation in anti-HPA-1a IgG greatly influences its binding to leukocyte IgG-Fc receptors IIIa/b. A cellular surface plasmon resonance imaging technique was developed to quantify the biological activity of IgG antibodies targeting cells.
FRONTIERS IN IMMUNOLOGY
(2023)
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
Gastroenterology & Hepatology
Archana Shubhakar, Bas C. Jansen, Alex T. Adams, Karli R. Reiding, Nicholas T. Ventham, Rahul Kalla, Daniel Bergemalm, Paulina A. Urbanowicz, Richard A. Gardner, Manfred IBD BIOM Consortium, Manfred Wuhrer, Jonas Halfvarson, Jack Satsangi, Daryl L. Fernandes, Daniel I. R. Spencer
Summary: This study investigated a composite serum N-glycomic biomarker to predict future disease course in newly diagnosed IBD patients. The biomarker showed a predictive capacity for treatment escalation in both the discovery and replication cohorts of patients.
JOURNAL OF CROHNS & COLITIS
(2023)