Article
Biochemistry & Molecular Biology
Gilles Thibault, Gilles Paintaud, Hsueh Cheng Sung, Laurie Lajoie, Edouard Louis, Celine Desvignes, Herve Watier, Valerie Gouilleux-Gruart, David Ternant
Summary: Fc gamma RIIA/CD32A is expressed on platelets and some endothelial cells, playing a role in binding IgG antibodies, which may contribute to their elimination. Platelet Fc gamma RIIA's affinity for different IgG subclasses influences the clearance of antibodies like infliximab.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Alessia Gravina, Grigol Tediashvili, Raja Rajalingam, Zoe Quandt, Chad Deisenroth, Sonja Schrepfer, Tobias Deuse
Summary: Engineered overexpression of CD64 protects cells from antibody-mediated killing, enhancing the efficacy of allogeneic cell therapeutics for cancer therapy or regenerative medicine.
NATURE BIOTECHNOLOGY
(2023)
Article
Neurosciences
Evan C. Rosenberg, Simon Chamberland, Michael Bazelot, Erica R. Nebet, Xiaohan Wang, Sam McKenzie, Swati Jain, Stuart Greenhill, Max Wilson, Nicole Marley, Alejandro Salah, Shanice Bailey, Pabitra Hriday Patra, Rebecca Rose, Nicolas Chenouard, Simon(e) D. Sun, Drew Jones, Gyorgy Buzsaki, Orrin Devinsky, Gavin Woodhall, Helen E. Scharfman, Benjamin J. Whalley, Richard W. Tsien
Summary: CBD reduces seizures in pediatric epilepsies, possibly by blocking the effects of LPI at synapses and reducing hyperexcitability.
Article
Chemistry, Multidisciplinary
Fan Liu, Li Zhang, Si Su, Yehong Fang, Xiang-sha Yin, Huan Cui, Jianru Sun, Yikuan Xie, Chao Ma
Summary: Neuropathic pain is difficult to treat and its mechanisms are not well understood. This study shows that neuronal Fc gamma RI plays an important role in neuropathic pain.
Article
Medicine, General & Internal
Joerg Hoffmann, Rojin Etati, Cornelia Brendel, Andreas Neubauer, Elisabeth Mack
Summary: Hyperinflammation through neutrophil granulocytes contributes to disease severity in COVID-19 pneumonia and promotes acute lung failure. Understanding the dysregulations within the myeloid cell compartment may help to improve therapies for severe COVID-19 infection.
Article
Oncology
Hallie M. Hintz, Kristin M. Snyder, Jianming Wu, Robert Hullsiek, James D. Dahlvang, Geoffrey T. Hart, Bruce Walcheck, Aaron M. LeBeau
Summary: The study engineered NK cells to express CD64 and bind antibodies for tumor targeting in mCRPC, showing enhanced cytotoxicity through ADCC. Targeting prostate tumor antigen TROP2 and fibroblast marker FAP, the combination approach demonstrated significantly higher cytotoxicity compared to single mAbs and NK cells alone, suggesting a potential immunotherapy for mCRPC.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Cell Biology
Christopher Beneduce, Stephanie Nguyen, Nathaniel Washburn, John Schaeck, Robin Meccariello, Kimberly Holte, Daniel Ortiz, Anthony M. Manning, Carlos J. Bosques, Elma Kurtagic
Summary: Fc glycosylation is crucial for antibody activity, and Fc sialylation is important for anti-inflammatory effects of IgGs. However, in vitro models using monomeric forms of antibodies have limited ability to determine the structure-activity relationship of Fc glycosylation. To overcome this, we utilized Fc-containing molecules displayed in monovalent and multivalent forms, and found that sialic acid mediates the phosphorylation of Fc?RIIb when IgG-Fc is displayed in a multivalent manner. This study provides new insights into the impact of Fc sialylation on immune cell signaling and characterization of anti-inflammatory activity of Fc-containing therapeutics.
Article
Immunology
Robert Hullsiek, Yunfang Li, Kristin M. Snyder, Sam Wang, Da Di, Antonella Borgatti, Chae Lee, Peter F. Moore, Cong Zhu, Chiara Fattori, Jaime F. Modiano, Jianming Wu, Bruce Walcheck
Summary: Researchers have cloned canine CD16A and CD64 and generated specific monoclonal antibodies. They have reported for the first time the expression patterns of these Fc gamma receptors on dog peripheral blood leukocytes. These findings pave the way for developing engineered canine NK cells or T cells with high affinity recombinant canine CD64 to enhance antibody-dependent cell-mediated cytotoxicity (ADCC).
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Celine Monnet, Emilie Jacque, Christophe de Romeuf, Alexandre Fontayne, Toufik Abache, Nathalie Fournier, Gilles Dupont, Delphine Derache, Anais Engrand, Aurelie Bauduin, Aurelie Terrier, Alexander Seifert, Cecile Beghin, Alain Longue, Nicholas Masiello, Laetitia Danino, Michel Nogre, Anais Raia, Frederic Dhainaut, Louis Fauconnier, Dieudonnee Togbe, Carmen Reitinger, Falk Nimmerjahn, Wil Stevens, Sami Chtourou, Philippe Mondon
Summary: Recently developed novel molecules targeting FcRn and/or Fc gamma R receptors show promising potential in treating IgG-dependent autoimmune pathologies. One of these molecules, LFBD192, engineered for optimal binding to both human and mouse Fc receptors, demonstrates superior efficacy compared to existing treatments like IVIg and FcRn blockers, and has been validated in vitro and in mouse models of autoimmune disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Isabell Lang, Olena Zaitseva, Harald Wajant
Summary: Inhibitory targeting of the CD40L-CD40 system is a promising therapeutic option in organ transplantation and autoimmune diseases. Lack of Fc gamma receptor (Fc gamma R)-binding is crucial for the development of safe inhibitory antibodies targeting CD40L or CD40. Recent clinical studies have shown that blocking CD40 antibodies not interacting with Fc gamma Rs are well tolerated and have initial clinical efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Eda Capkin, Asli Kutlu, Meral Yuce
Summary: This study investigates the potential of repurposing Fc gamma RI as an analytical ligand molecule for monoclonal antibody-based biosensing. It demonstrates successful site-oriented antibody capture and real-time detection of the corresponding analyte molecule. The findings suggest that Fc gamma RI has the potential to serve as a universal ligand molecule with excellent selectivity and low nanomolar range affinity. However, surface stability and sensing response can be further improved, and further studies are required to assess its performance with different monoclonal antibodies.
Article
Immunology
Daniel L. Seiler, Katja H. Kaehler, Marie Kleingarn, Christian D. Sadik, Katja Bieber, Joerg Koehl, Ralf J. Ludwig, Christian M. Karsten
Summary: This study demonstrates the important role of C5aR2 in regulating the activation and function of neutrophils in response to C5a, and its potential impact on the expression of Fc gamma receptors and CD11b. These findings highlight the significance of C5aR2 in the pathogenesis of neutrophil-mediated autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Itziar Ibarlucea-Benitez, Polina Weitzenfeld, Patrick Smith, Jeffrey Ravetch
Summary: Targeting myeloid receptors Siglec-7 and Siglec-9 shows therapeutic potential in enhancing antitumor immunity, although their effectiveness is influenced by the tumor microenvironment. Development of Fc engineered blocking antibodies against Siglec-7 and Siglec-9 significantly reduces tumor burden, demonstrating their potential as immunotherapy targets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Bettina Groetsch, Elisabeth Schachtschabel, Philipp Tripal, Benjamin Schmid, Ana-Suncana Smith, Georg Schett, Aline Bozec
Summary: The differentiation and activity of osteoclasts are co-influenced by Fc gamma R and IFN gamma R signaling pathways, depending on the differentiation state of osteoclasts. The different stages may reflect distinct situations in rheumatoid arthritis (RA).
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Alistair Noble, Basudev Paudyal, John C. Schwartz, William Mwangi, Danish Munir, Elma Tchilian, John A. Hammond, Simon P. Graham
Summary: Cattle possess three IgG subclasses with different functionalities, which differ from those described in humans, mice, or pigs. This has important implications for the development of vaccines and therapeutic antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Marlene Schwarzfischer, Anna Niechcial, Kristina Handler, Yasser Morsy, Marcin Wawrzyniak, Andrea S. Laimbacher, Kirstin Atrott, Roberto Manzini, Katharina Baebler, Larissa Hering, Egle Katkeviciute, Janine Hafliger, Silvia Lang, Maja E. Keller, Jerome Woodtli, Lisa Eisenbeiss, Thomas Kraemer, Elisabeth M. Schraner, Mahesa Wiesendanger, Sebastian Zeissig, Gerhard Rogler, Andreas E. Moor, Michael Scharl, Marianne R. Spalinger
Summary: This study investigates the interaction between the PTPN22 gene variation and food-grade titanium dioxide nanoparticles in the pathogenesis of inflammatory bowel disease (IBD). The results show that the ingestion of titanium dioxide nanoparticles makes mice carrying the PTPN22 variation susceptible to IBD and triggers severe intestinal inflammation. This demonstrates that environmental factors can interact with genetic risk variants and reverse a protective mechanism into a disease-promoting effect.
Article
Cell Biology
Daniela Lenggenhager, Jonas Grossmann, Jerome Gouttenoire, Christine Sempoux, Achim Weber
Summary: Immunohistochemistry for HEV ORF2 protein is a useful tool for tissue-based diagnosis of hepatitis E. However, we report an unexpected immunoreactivity of the HEV ORF2 antibody to CMV proteins. The staining pattern of CMV-infected cells is limited to the nucleus, in contrast to the cytoplasmic and occasional canalicular positivity observed in hepatitis E.
Article
Biochemistry & Molecular Biology
Laura J. Smith, Magdalena M. Bolsinger, Kai-Yin Chau, Matthew E. Gegg, Anthony H. Schapira
Summary: Sequence variants or mutations in the GBA gene are the most important risk factor for Parkinson's disease. This study characterizes the effects of the E326K variant in human cells and finds that it behaves differently compared to other common GBA mutations. However, lipid imbalance and alpha-synuclein pathology are still observed.
HUMAN MOLECULAR GENETICS
(2023)
Article
Gastroenterology & Hepatology
Joana Torres, Maria Chaparro, Mette Julsgaard, Konstantinos Katsanos, Zuzana Zelinkova, Manasi Agrawal, Sandro Ardizzone, Marjo Campmans-Kuijpers, Gabriele Dragoni, Marc Ferrante, Gionata Fiorino, Emma Flanagan, Catarina Frias Gomes, Ailsa Hart, Charlotte Rose Hedin, Pascal Juillerat, Annemarie Mulders, Par Myrelid, Aoibhlinn O'Toole, Pauline Riviere, Michael Scharl, Christian Philipp Selinger, Elena Sonnenberg, Murat Toruner, Jantien Wieringa, C. Janneke Van der Woude
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Cell Biology
Simon Haefliger, Juergen Hench, Colm J. O'Rourke, Nathalie Meyer-Schaller, Sarp Uzun, Joan Saldarriaga, Achim Weber, Luca Mazzucchelli, Philip Jermann, Stephan Frank, Jesper B. Andersen, Luigi Terracciano, Christine Sempoux, Matthias S. Matter
Summary: This study analyzed the genetic and epigenetic alterations of hepatocellular adenomas (HCA) with atypical morphological features, and found differences with hepatocellular carcinoma (HCC) or HCA without atypical morphology. Therefore, targeted sequencing and/or combined methylation/copy number profiling should be performed to differentiate between HCC and HCA when diagnosis is difficult.
Article
Gastroenterology & Hepatology
Janine Hafliger, Marlene Schwarzfischer, Kirstin Atrott, Claudia Stanzel, Yasser Morsy, Marcin Wawrzyniak, Silvia Lang, Tomas Valenta, Konrad Basler, Gerhard Rogler, Michael Scharl, Marianne R. Spalinger
Summary: The loss of GP96 in the adult mice intestine leads to the degeneration of the stem cell niche, the eradication of the epithelial layer, and ultimately death. This is due to defects in Wnt and Notch signaling, as well as massive induction of endoplasmic reticulum stress. GP96 also plays a critical role in regulating the renewal and differentiation of intestinal stem cells.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Clinical Neurology
Tom Foltynie, Sonia Gandhi, Cristina Gonzalez-Robles, Marie-Louise Zeissler, Georgia Mills, Roger Barker, James Carpenter, Anette Schrag, Anthony Schapira, Oliver Bandmann, Stephen Mullin, Joy Duffen, Kevin McFarthing, Jeremy Chataway, Mahesh Parmar, Camille Carroll
Summary: Multi-arm, multi-stage platform designs have improved the efficiency of clinical trials in the field of oncology. Foltynie et al. discuss the challenges and considerations of using this approach to assess potential disease-modifying treatments in progressive neurological conditions such as Parkinson's disease.
Article
Medicine, General & Internal
Audrey Kovatsch, Hanna Honcharova-Biletska, Daniel Segna, Klaus Steigmiller, Sena Bluemel, Rudolf A. Deibel, Tobias Kuehlewindt, Georg Leinenkugel, Sandra Mueller, Eva Furrer, Khoschy Schawkat, Caecilia S. Reiner, Achim Weber, Beat Muellhaupt, Michael Scharl, Christoph Gubler, Christoph Juengst
Summary: This study evaluated the diagnostic accuracy of 2D-SWE assessed by the Canon Aplio i800 ultrasound system in liver fibrosis and compared it with traditional liver histology and transient elastography (TE). The results showed that 2D-SWE had good to excellent performance in diagnosing significant fibrosis, severe fibrosis, and cirrhosis, and its accuracy was comparable to TE. Therefore, the 2D-SWE system has a promising potential in the diagnostic workup of chronic liver disease.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Gastroenterology & Hepatology
Anna Niechcial, Marlene Schwarzfischer, Marcin Wawrzyniak, Kirstin Atrott, Andrea Laimbacher, Yasser Morsy, Egle Katkeviciute, Janine Hafliger, Patrick Westermann, Cezmi A. Akdis, Michael Scharl, Marianne R. Spalinger
Summary: The study found that the polyamine spermidine can reduce intestinal inflammation by promoting the production of anti-inflammatory macrophages, maintaining a healthy gut microbiome, and preserving the integrity of the intestinal barrier, suggesting its potential therapeutic role in inflammatory bowel disease.
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Veterinary Sciences
Marianne Spalinger, Marlene Schwarzfischer, Anna Niechcial, Kirstin Atrott, Andrea Laimbacher, Paulin Jirkof, Michael Scharl
Summary: The use of analgesics in DSS-induced colitis models is currently discouraged due to potential interactions. However, this study found that tramadol and paracetamol can be viable options without interfering with colitis severity. Tramadol had minor effects on colitis, while paracetamol improved overall appearance. Metamizole, on the other hand, significantly reduced water uptake and caused weight loss.
LABORATORY ANIMALS
(2023)
Article
Clinical Neurology
Cornelis Blauwendraat, Nahid Tayebi, Elizabeth Geena Woo, Grisel Lopez, Luca Fierro, Marco Toffoli, Naomi Limbachiya, Derralynn Hughes, Vanessa Pitz, Dhairya Patel, Dan Vitale, Mathew J. Koretsky, Dena Hernandez, Raquel Real, Roy N. Alcalay, Mike A. Nalls, Huw R. Morris, Anthony H. V. Schapira, Manisha Balwani, Ellen Sidransky
Summary: This study found that PD patients with GD1 have a higher genetic risk score, suggesting that common risk variants may affect underlying biological pathways.
MOVEMENT DISORDERS
(2023)
Article
Gastroenterology & Hepatology
Daniel Schweckendiek, Dagmar Pauli, Michael Scharl
Summary: Eating disorders, including anorexia nervosa, bulimia nervosa, binge eating disorder, and avoidant restrictive food intake disorder, are potentially life-threatening with severe psychiatric and somatic comorbidities. The number of patients is expected to increase significantly in the post COVID-19 pandemic era. This article focuses on the gastroenterologic aspects and complications of eating disorders, rather than the psychiatric treatment. The role of gastroenterologists in managing these complications is crucial.
ZEITSCHRIFT FUR GASTROENTEROLOGIE
(2023)
Letter
Clinical Neurology
Marco Toffoli, Anthony H. V. Schapira, Christos Proukakis
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Siegfried Karl Wagner, David Romero-Bascones, Mario Cortina-Borja, Dominic J. Williamson, Robbert R. Struyven, Yukun Zhou, Salil Patel, Rimona S. Weil, Chrystalina A. Antoniades, Eric J. Topol, Edward Korot, Paul J. Foster, Konstantinos Balaskas, Unai Ayala, Maitane Barrenechea, Inigo Gabilondo, Anthony H. V. Schapira, Anthony P. Khawaja, Praveen J. Patel, Jugnoo S. Rahi, Alastair K. Denniston, Axel Petzold, Pearse Andrew Keane
Summary: Individuals with Parkinson's disease (PD) exhibit reduced thickness of the inner nuclear layer (INL) and ganglion cell-inner plexiform layer (GCIPL) of the retina. Changes in these layers occurring several years before clinical presentation highlight a potential role for retinal imaging in stratifying PD risk.
Article
Clinical Neurology
Cornelis Blauwendraat, Nahid Tayebi, Elizabeth Geena Woo, Grisel Lopez, Luca Fierro, Marco Toffoli, Naomi Limbachiya, Derralynn Hughes, Vanessa Pitz, Dhairya Patel, Dan Vitale, Mathew J. Koretsky, Dena Hernandez, Raquel Real, Roy N. Alcalay, Mike A. Nalls, Huw R. Morris, Anthony H. V. Schapira, Manisha Balwani, Ellen Sidransky
Summary: This study investigated the contribution of PD risk variants to risk for PD in patients with GD1. The results showed that patients with GD1 who developed PD had a significantly higher PD genetic risk score than those without PD. This suggests that common risk variants may affect underlying biological pathways.
MOVEMENT DISORDERS
(2023)