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
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)
Article
Biochemical Research Methods
K. Madunic, Y. M. C. A. Luijkx, O. A. Mayboroda, G. M. C. Janssen, P. A. van Veelen, K. Strijbis, T. Wennekes, G. S. M. Lageveen-Kammeijer, M. Wuhrer
Summary: This study identified specific mucin O-glycans that mark butyrate-induced epithelial differentiation of the intestinal cell line CaCo-2 using porous graphitized carbon nano-liquid chromatography with electrospray ionization tandem mass spectrometry. The results showed that the fully differentiated butyrate-stimulated cells have a higher expression of sialylated O-glycan structures, while fucosylation is downregulated during differentiation. These findings provide insights into the dynamic O-glycosylation patterns in the gut and their functional role in gut-microbiota homeostasis and dysbiosis.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Review
Rheumatology
Theresa Kissel, Rene E. M. Toes, Thomas W. J. Huizinga, Manfred Wuhrer
Summary: Glycosylation is a common modification that affects protein stability and interactions. It plays a significant role in rheumatic diseases, influencing inflammatory processes and disease progression. Understanding the impact of glycosylation on plasma proteins, cells, and tissues opens up potential interventions for the treatment of these diseases.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Chemistry, Analytical
Guusje van Schaick, Elena Dominguez-Vega, Jerome Castel, Manfred Wuhrer, Oscar Hernandez-Alba, Sarah Cianferani
Summary: Post-translational modifications (PTMs) increase protein structural heterogeneity and can alter conformation and biological functions. Monitoring PTMs is crucial for therapeutic products like monoclonal antibodies (mAbs). Cation-exchange chromatography (CEX) with native mass spectrometry is valuable for characterizing mAb charge variants, but cannot explore protein conformation. To address this, we combined CEX separation with collision-induced unfolding (CIU) experiments to monitor conformational differences without compromising CEX resolution. This strategy enabled in-depth characterization of mAb glycoforms and linking conformational changes to resistance against gas-phase unfolding charge variants.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Constantin Blochl, Di Wang, Oleg A. Mayboroda, Guinevere S. M. Lageveen-Kammeijer, Manfred Wuhrer
Summary: In this study, a meta-omics approach was used to investigate the glycomic landscape of AML. Specific glycosyltransferases and transcription factors associated with glycan phenotypes were identified. The study also found distinct glycomic features in subtypes M5 and M6 of AML, as well as similar gene expression patterns and regulatory networks in primary AML cells.
CELL AND BIOSCIENCE
(2023)
Article
Cell Biology
Ruiyao Xu, Xianxian Wang, Sadia Safi, Nico Braunegger, Agnes Hipgrave Ederveen, Michelle Rottmann, Joachim Wittbrodt, Manfred Wuhrer, Janine Wesslowski, Gary Davidson
Summary: Reception of Wnt signals is mediated by Frizzled receptors and a co-receptor LRP6 or LRP5. Precise control of receptor activation is crucial to regulate Wnt/beta-catenin signaling for proper cellular function. A glycosyltransferase B3GnT2-like has been identified to modify LRP6 and enhance Wnt/beta-catenin signaling. This study highlights the importance of LRP6 as a regulatory hub in Wnt signaling and provides insight into the selective targeting of a signaling pathway component by a specific glycosyltransferase.
Article
Biochemistry & Molecular Biology
Alan B. Moran, Georgia Elgood-Hunt, Yuri E. M. van der Burgt, Manfred Wuhrer, Wilma E. Mesker, Rob A. E. M. Tollenaar, Daniel I. R. Spencer, Guinevere S. M. Lageveen-Kammeijer
Summary: A newly developed analytical strategy was used to analyze the N-glycome of colorectal cancer (CRC) patients before and after surgery. The strategy involved fluorescent labeling and specific derivatization techniques, allowing for efficient separation and detection. The results showed changes in N-glycan structures, which may have implications for CRC classification and clinical data analysis. This strategy can be used to monitor patient profiles during and after clinical events and warrants further investigation.
Article
Chemistry, Analytical
Guusje van Schaick, Manfred Wuhrer, Elena Dominguez-Vega
Summary: Proteins undergo various post-translational modifications (PTMs) which can affect their stability and activity. Native separation techniques coupled with mass spectrometry (MS) have proven to be a powerful tool for investigating the structure-function relationship of PTMs. In this study, the researchers explored the use of dopant-enriched nitrogen gas to improve the nano-electrospray ionization (nano-ESI)-MS of native proteins, particularly glycoproteins. They found that the use of DEN gas resulted in lower charge states and less adduct formation, leading to improved ionization efficiency and spectral quality for highly glycosylated proteins.
ANALYTICA CHIMICA ACTA
(2023)
Article
Endocrinology & Metabolism
Elham Memarian, Ralph Heijmans, Roderick C. Slieker, Adriana Sierra, Olga Gornik, Joline W. J. Beulens, Maja Hanic, Petra Elders, Julio Pascual, Eric Sijbrands, Gordan Lauc, Viktoria Dotz, Clara Barrios, Leen M. 't Hart, Manfred Wuhrer, Mandy van Hoek
Summary: Inflammation plays an important role in the development of type 2 diabetes complications, and the N-glycosylation of IgG affects its role in inflammation. This study found that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes.
DIABETES-METABOLISM RESEARCH AND REVIEWS
(2023)
Article
Chemistry, Applied
Guusje van Schaick, Sanne Pot, Olaf Schouten, Joost den Hartog, Michiel Akeroyd, Rob van der Hoeven, Wim Bijleveld, Nicolas Abello, Manfred Wuhrer, Maurien Olsthoorn, Elena Dominguez-Vega
Summary: Protein glycation is a natural process in industrial enzymes and its impact on enzyme performance is unpredictable. A boronate affinity chromatography method was developed to analyze the influence of glycation on enzyme activity and stability. The results showed that glycation did not affect the performance of the lipase.
Article
Biochemistry & Molecular Biology
Annemieke Naber, Daniel Demus, Roderick Slieker, Simone Nicolardi, Joline W. J. Beulens, Petra J. M. Elders, Aloysius G. Lieverse, Eric J. G. Sijbrands, Leen M. 't Hart, Manfred Wuhrer, Mandy van Hoek
Summary: This study aimed to investigate the impact of apo-CIII glycosylation on lipid traits and type 2 diabetes prevalence. The researchers conducted a GWAS on different apo-CIII proteoforms and identified genetic loci associated with glycosylation and its relation to lipids and diabetes. The study confirmed the significant role of GALNT2 gene in apo-CIII O-glycosylation and its association with lipid parameters. Additionally, the IFT172/NRBP1 region was found to be involved in apo-CIII sialylation and hypertriglyceridemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Oleg A. Mayboroda, Guinevere S. M. Lageveen-Kammeijer, Manfred Wuhrer, Radboud J. E. M. Dolhain
Summary: Rheumatoid arthritis (RA) is a prevalent autoimmune disease affecting joints and other organs. Glycosylation changes in immunoglobulin G (IgG) and immunoglobulin A (IgA) have been found in RA patients, which can be used as biomarkers to differentiate patients and predict disease activity.
Article
Immunology
Jana Sophia Buhre, Tamas Pongracz, Inga Kuensting, Anne S. S. Lixenfeld, Wenjun Wang, Jan Nouta, Selina Lehrian, Franziska Schmelter, Hanna B. B. Lunding, Lara Duehring, Carsten Kern, Janina Petry, Emily L. L. Martin, Bandik Foeh, Moritz Steinhaus, Vera von Kopylow, Christian Sina, Tobias Graf, Johann Rahmoeller, Manfred Wuhrer, Marc Ehlers
Summary: This study investigated the long-term antibody response to new mRNA-containing lipid nanoparticle vaccines and adenovirus-based vaccines. The study found that the antibody levels induced by mRNA vaccines decreased over time, while the levels induced by adenovirus-based vaccines remained stable. mRNA vaccines also induced a long-term IgG4 antibody response, which may affect long-term efficacy. These findings have potential implications for the long-term effectiveness of these novel vaccines.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Engineering, Multidisciplinary
Wei Wang, Tao Zhang, Jan Nouta, Peter A. van Veelen, Noortje de Haan, Theo M. de Reijke, Manfred Wuhrer, Guinevere S. M. Lageveen-Kammeijer
Summary: This research confirms for the first time the presence of Kdn on the glycans of human prostate-specific antigen (PSA) and suggests its potential relevance to prostate cancer. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of Kdn in humans.
