Article
Hematology
Billy Michael Chelliah Jebaraj, Annika Mueller, Rashmi Priyadharshini Dheenadayalan, Sascha Endres, Philipp M. Roessner, Felix Seyfried, Claudia Walliser, Martin Wist, Jialei Qi, Eugen Tausch, Daniel Mertens, Judith A. Fox, Klaus-Michael Debatin, Luder Hinrich Meyer, Pietro Taverna, Martina Seiffert, Peter Gierschik, Stephan Stilgenbauer
Summary: Vecabrutinib, a noncovalent BTK inhibitor, may be effective in treating C481S BTK mutant CLL while preserving the T-cell immunomodulatory function of ibrutinib.
Article
Medicine, Research & Experimental
Julia Zinngrebe, Barbara Moepps, Thomas Monecke, Peter Gierschik, Ferdinand Schlichtig, Thomas F. E. Barth, Gudrun Strauss, Elena Boldrin, Carsten Posovszky, Ansgar Schulz, Ortraud Beringer, Eva Rieser, Eva-Maria Jacobsen, Myriam Ricarda Lorenz, Klaus Schwarz, Ulrich Pannicke, Henning Walczak, Dierk Niessing, Catharina Schuetz, Pamela Fischer-Posovszky, Klaus-Michael Debatin
Summary: This article describes an atypical clinical manifestation of OTULIN-related autoinflammatory syndrome (ORAS) caused by new compound heterozygous variants (c.258G>A (p.M86I)/c.500G>C (p.W167S)) in the OTULIN gene. The study found that these variants compromised the binding of OTULIN to linear ubiquitin, leading to the development of the disease.
EMBO MOLECULAR MEDICINE
(2022)
Article
Immunology
Akua A. Karikari, Rhonda L. McFleder, Eliana Ribechini, Robert Blum, Valentin Bruttel, Susanne Knorr, Mona Gehmeyr, Jens Volkmann, Jonathan M. Brotchie, Fadhil Ahsan, Beatrice Haack, Camelia-Maria Monoranu, Ursula Keber, Rima Yeghiazaryan, Axel Pagenstecher, Tobias Heckel, Thorsten Bischler, Joerg Wischhusen, James B. Koprich, Manfred B. Lutz, Chi Wang Ip
Summary: The study confirms that alpha-synuclein-specific T cell responses can cause dopaminergic neurodegeneration and contribute to the pathogenesis of Parkinson's disease (PD) in a mouse model.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Immunology
Laura Cyran, Julia Serfling, Luisa Kirschner, Hartmann Raifer, Michael Lohoff, Heike M. Hermanns, Andreas Kerstan, Jochen Bodem, Manfred B. Lutz
Summary: FL10 selectively promotes the development and survival of cDC2 subset in bone marrow cells, which exhibit unique characteristics in the expression of transcription factors and immune response compared to other cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Monika Kustermann, Prasad Dasari, Ingrid Knape, Emma Keltsch, Jianing Liu, Silvia Pfluger, Wolfram Osen, Karlheinz Holzmann, Markus Huber-Lang, Klaus-Michael Debatin, Gudrun Strauss
Summary: Immune reactions after trauma lead to an imbalanced immunohomeostasis and immunosuppression, increasing susceptibility to secondary infections. The immunomodulatory capacity of myeloid-derived suppressor cells (MDSCs) after trauma is not well-defined. However, studies have shown that therapeutic MDSC treatment can improve post-traumatic T-cell functions and enhance the ability to respond to secondary antigen challenges.
JOURNAL OF INNATE IMMUNITY
(2023)
Article
Multidisciplinary Sciences
Eva-Maria Jacobsen, Dorit Fabricius, Magdalena Class, Fernando Topfstedt, Raquel Lorenzetti, Iga Janowska, Franziska Schmidt, Julian Staniek, Maria Zernickel, Thomas Stamminger, Andrea N. Dietz, Angela Zellmer, Manuel Hecht, Peter Rauch, Carmen Blum, Carolin Ludwig, Bernd Jahrsdoerfer, Hubert Schrezenmeier, Maximilian Heeg, Benjamin Mayer, Alina Seidel, Ruediger Gross, Jan Muench, Frank Kirchhoff, Sebastian F. N. Bode, Gudrun Strauss, Hanna Renk, Roland Elling, Maximillian Stich, Reinhard E. Voll, Burkhard Toenshof, Axel R. Franz, Philipp Henneke, Klaus-Michael Debatin, Marta Rizzi, Ales Janda
Summary: The severity and immune response of SARS-CoV-2 infection differ in adults and children. Children show a plasmablast-driven initial response, enhanced specific antibody response, and lower but detectable specific B and T cell responses compared to their parents. After one year, children exhibit an increase in S1-specific IgA class switch and enhanced T cell maturation.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Ilio Vitale, Federico Pietrocola, Emma Guilbaud, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Massimiliano Agostini, Patrizia Agostinis, Emad S. Alnemri, Lucia Altucci, Ivano Amelio, David W. Andrews, Rami Aqeilan, Eli Arama, Eric H. Baehrecke, Siddharth Balachandran, Daniele Bano, Nickolai A. Barlev, Jiri Bartek, Nicolas G. Bazan, Christoph Becker, Francesca Bernassola, Mathieu J. M. Bertrand, Marco E. Bianchi, Mikhail V. Blagosklonny, J. Magarian Blander, Giovanni Blandino, Klas Blomgren, Christoph Borner, Carl D. Bortner, Pierluigi Bove, Patricia Boya, Catherine Brenner, Petr Broz, Thomas Brunner, Rune Busk Damgaard, George A. Calin, Michelangelo Campanella, Eleonora Candi, Michele Carbone, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K-M Chan, Guo-Qiang Chen, Quan Chen, Youhai H. Chen, Emily H. Cheng, Jerry E. Chipuk, John A. Cidlowski, Aaron Ciechanover, Gennaro Ciliberto, Marcus Conrad, Juan R. Cubillos-Ruiz, Peter E. Czabotar, Vincenzo D'Angiolella, Mads Daugaard, Ted M. Dawson, Valina L. Dawson, Ruggero De Maria, Bart De Strooper, Klaus-Michael Debatin, Ralph J. Deberardinis, Alexei Degterev, Giannino Del Sal, Mohanish Deshmukh, Francesco Di Virgilio, Marc Diederich, Scott J. Dixon, Brian D. Dynlacht, Wafik S. El-Deiry, John W. Elrod, Kurt Engeland, Gian Maria Fimia, Claudia Galassi, Carlo Ganini, Ana J. Garcia-Saez, Abhishek D. Garg, Carmen Garrido, Evripidis Gavathiotis, Motti Gerlic, Sourav Ghosh, Douglas R. Green, Lloyd A. Greene, Hinrich Gronemeyer, Georg Haecker, Gyorgy Hajnoczky, J. Marie Hardwick, Ygal Haupt, Sudan He, David M. Heery, Michael O. Hengartner, Claudio Hetz, David A. Hildeman, Hidenori Ichijo, Satoshi Inoue, Marja Jaeaettelae, Ana Janic, Bertrand Joseph, Philipp J. Jost, Thirumala-Devi Kanneganti, Michael Karin, Hamid Kashkar, Thomas Kaufmann, Gemma L. Kelly, Oliver Kepp, Adi Kimchi, Richard N. Kitsis, Daniel J. Klionsky, Ruth Kluck, Dmitri Krysko, Dagmar Kulms, Sharad Kumar, Sergio Lavandero, Inna N. Lavrik, John J. Lemasters, Gianmaria Liccardi, Andreas Linkermann, Stuart A. Lipton, Richard A. Lockshin, Carlos Lopez-Otin, Tom Luedde, Marion MacFarlane, Frank Madeo, Walter Malorni, Gwenola Manic, Roberto Mantovani, Saverio Marchi, Jean-Christophe Marine, Seamus J. Martin, Jean-Claude Martinou, Pier G. Mastroberardino, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Gerry Melino, Sonia Melino, Edward A. Miao, Ute M. Moll, Cristina Munoz-Pinedo, Daniel J. Murphy, Maria Victoria Niklison-Chirou, Flavia Novelli, Gabriel Nunez, Andrew Oberst, Dimitry Ofengeim, Joseph T. Opferman, Moshe Oren, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M. Penninger, Francesca Pentimalli, David M. Pereira, Shazib Pervaiz, Marcus E. Peter, Paolo Pinton, Giovanni Porta, Jochen H. M. Prehn, Hamsa Puthalakath, Gabriel A. Rabinovich, Krishnaraj Rajalingam, Kodi S. Ravichandran, Markus Rehm, Jean-Ehrland Ricci, Rosario Rizzuto, Nirmal Robinson, Cecilia M. P. Rodrigues, Barak Rotblat, Carla Rothlin, David C. Rubinsztein, Thomas Rudel, Alessandro Rufini, Kevin M. Ryan, Kristopher A. Sarosiek, Akira Sawa, Emre Sayan, Kate Schroder, Luca Scorrano, Federico Sesti, Feng Shao, Yufang Shi, Giuseppe S. Sica, John Silke, Hans-Uwe Simon, Antonella Sistigu, Anastasis Stephanou, Brent R. Stockwell, Flavie Strapazzon, Andreas Strasser, Liming Sun, Erwei Sun, Qiang Sun, Gyorgy Szabadkai, Stephen W. G. Tait, Daolin Tang, Nektarios Tavernarakis, Carol M. Troy, Boris Turk, Nicoletta Urbano, Peter Vandenabeele, Tom Vanden Berghe, Matthew G. Vander Heiden, Jacqueline L. Vanderluit, Alexei Verkhratsky, Andreas Villunger, Silvia von Karstedt, Anne K. Voss, Karen H. Vousden, Domagoj Vucic, Daniela Vuri, Erwin F. Wagner, Henning Walczak, David Wallach, Ruoning Wang, Ying Wang, Achim Weber, Will Wood, Takahiro Yamazaki, Huang-Tian Yang, Zahra Zakeri, Joanna E. Zawacka-Pankau, Lin Zhang, Haibing Zhang, Boris Zhivotovsky, Wenzhao Zhou, Mauro Piacentini, Guido Kroemer, Lorenzo Galluzzi
Summary: Apoptosis is a regulated cell death process involving caspase family proteases. Inhibiting or delaying apoptosis experimentally through pharmacological and genetic strategies has demonstrated its importance in embryonic development, tissue homeostasis, and the pathogenesis of various human disorders. Defects in apoptotic cell death machinery impair development and promote oncogenesis, while inappropriate activation of apoptosis contributes to cell loss and tissue damage in neurological, cardiovascular, renal, hepatic, infectious, neoplastic, and inflammatory conditions.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Hematology
Amadeus T. Heinz, Friso G. J. Calkoen, Alexander Derbich, Lea Miltner, Christian Seitz, Michaela Doering, Christiane Braun, Daniel Atar, Michael Schumm, Florian Heubach, Anne- Marie Arendt, Ansgar Schulz, Friedhelm R. Schuster, Roland Meisel, Brigitte Strahm, Juergen Finke, Beatrice Heineking, Susanne Stetter, Gerda Silling, Daniel Stachel, Bernd Gruhn, Klaus-Michael Debatin, Juergen Foell, Johannes H. Schulte, Wilhelm Woessmann, Christine Mauz-Koerholz, Johanna Tischer, Tobias Feuchtinger, Rupert Handgretinger, Peter Lang
Summary: Therapy-resistant viral reactivations after hematopoietic stem cell transplantation can be effectively reduced by adoptive cellular therapy with virus-specific T cells. In this study, the in-house production of virus-specific T cells in a closed system was successful and showed favorable safety profile and efficacy in 26 patients.
Article
Medicine, General & Internal
Jan-Bernd Funcke, Barbara Moepps, Julian Roos, Julia von Schnurbein, Kenneth Verstraete, Elke Froehlich-Reiterer, Katja Kohlsdorf, Adriana Nunziata, Stephanie Brandt, Alexandra Tsirigotaki, Ann Dansercoer, Elisabeth Suppan, Basma Haris, Klaus-Michael Debatin, Savvas N. Savvides, I. Sadaf Farooqi, Khalid Hussain, Peter Gierschik, Pamela Fischer-Posovszky, Martin Wabitsch
Summary: This article describes two novel homozygous leptin variants that caused intense hyperphagia, severe obesity, and high leptin levels in two unrelated children. These variants bind to the leptin receptor but have marginal signaling. In the presence of nonvariant leptin, they act as competitive antagonists. High-dose recombinant leptin treatment was initiated and gradually reduced, resulting in near-normal weight for both patients. Antidrug antibodies developed in the patients, but did not appear to affect efficacy. No severe adverse events were observed.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Pediatrics
Alina Seidel, Eva-Maria Jacobsen, Dorit Fabricius, Magdalena Class, Maria Zernickel, Carmen Blum, Carina Conzelmann, Tatjana Weil, Ruediger Gross, Sebastian F. N. Bode, Hanna Renk, Roland Elling, Maximillian Stich, Frank Kirchhoff, Klaus-Michael Debatin, Jan Muench, Ales Janda
Summary: This study investigated the serum neutralization capacity and T cell memory responses of 36 seropositive adults and 34 children approximately one year after infection with the ancestral Wuhan strain of SARS-CoV-2. The results showed that a high percentage of both adults and children retained neutralizing activity against the SARS-CoV-2 Wuhan strain, although the neutralization effect against the Omicron BA.1 variant was lower. Additionally, specific T cell memory responses against the Wuhan strain and the BA.1 variant were detected in both adults and children.
FRONTIERS IN PEDIATRICS
(2023)
Correction
Oncology
N. Gassler, C. Zhang, T. Wenger, P. A. Schnabel, H. Dienemann, K-M Debatin, J. Mattern, I. Herr
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Vladimir G. Magalhaes, Soeren Lukassen, Maike Drechsler, Jennifer Loske, Sandy S. Burkart, Sandra Wuest, Eva-Maria Jacobsen, Jobst Roehmel, Marcus A. Mall, Klaus-Michael Debatin, Roland Eils, Stella Autenrieth, Ales Janda, Irina Lehmann, Marco Binder
Summary: Children have a stronger innate immune response and enhanced cytokine-mediated interactions with epithelial cells, which may explain their remarkable resistance to COVID-19.
Article
Health Care Sciences & Services
Mike-Andrew Westhoff, Carsten Posovszky, Klaus-Michael Debatin
Summary: Vaccines are highly effective in saving lives, but unfortunately they are often met with more controversy than their safety profile justifies. The anti-vaccine movement has evolved through three generations, with the current generation being closely associated with the broader anti-COVID movement and promoting individualism over community health. It is crucial to provide better science education to the young and the general public to improve overall science literacy, and strategies to achieve this are suggested.
INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING
(2023)
Article
Immunology
Victor G. Lui, Manfred Hoenig, Berenice Cabrera-Martinez, Ryan M. Baxter, Josselyn E. Garcia-Perez, Olivia Bailey, Atanu Acharya, Karl Lundquist, Jesusa Capera, Paul Matusewicz, Frederike A. Hartl, Marco D'Abramo, Josephine Alba, Eva-Maria Jacobsen, Doris Niewolik, Myriam Lorenz, Ulrich Pannicke, Ansgar S. Schulz, Klaus-Michael Debatin, Wolfgang W. Schamel, Susana Minguet, James C. Gumbart, Michael L. Dustin, John C. Cambier, Klaus Schwarz, Elena W. Y. Hsieh
Summary: A novel LCK variant, P440S, leads to T cell dysfunction, causing recurrent infections, failure to thrive, and intestinal inflammation in infants.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Oncology
Lara Rieh, Medhanie Mulaw, Katharina Kneer, Meinhard Beer, Ambros Beer, Thomas F. Bart, Vladimir Benes, Johannes Schulte, Matthias Fischer, Klaus-Michael Debatin, Christian Beltinger
Summary: In this study, tumor-associated mt and nuclear circulating variants were detected in a minority of NB patients, but the number and allelic frequency of the circulating variants did not reflect the clinical course of the tumors.