Article
Biochemistry & Molecular Biology
Jens Van Bael, Aline Vandenbulcke, Abdelhakim Ahmed-Belkacem, Jean-Francois Guichou, Jean-Michel Pawlotsky, Jelle Samyn, Arjan D. Barendrecht, Coen Maas, Simon F. De Meyer, Karen Vanhoorelbeke, Claudia Tersteeg
Summary: Inhibiting CypD activity with novel non-immunosuppressive cyclophilin inhibitors (SMCypIs) can effectively reduce procoagulant platelet formation and provide a promising strategy for limiting thrombosis without affecting normal platelet function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Guenalp Uzun, Lisann Pelzl, Anurag Singh, Tamam Bakchoul
Summary: Both qualitative and quantitative platelet abnormalities are common in COVID-19 patients, and they are associated with clinical severity and mortality. Activated platelets contribute to the prothrombotic state in COVID-19 patients. Immune-mediated activation of platelets has been observed in critically ill COVID-19 patients. Platelet consumption and thrombosis occur due to activation of platelets by immune complexes through FcγRIIA. A better understanding of platelet activation in COVID-19 and vaccine-induced thrombotic complications will have therapeutic implications.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Christopher W. Smith, Maan H. Harbi, Lourdes Garcia-Quintanilla, Kieran Rookes, Helena Brown, Natalie S. Poulter, Steve P. Watson, Phillip L. R. Nicolson, Mark R. Thomas
Summary: LH34 potently inhibits atherosclerotic plaque-induced thrombus formation and procoagulant platelet activity in vitro with less off-target inhibition of Src than ibrutinib, suggesting it is a promising antiplatelet therapy with the potential for reduced bleeding side effects.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Immunology
Bo Nilsson, Oskar Eriksson, Karin Fromell, Barbro Persson, Kristina N. N. Ekdahl
Summary: COVID-19 has a complex impact on the immune system, with severe cases showing strong activation of the intravascular innate immune system (IIIS) which may contribute to the severity of the disease. This article describes the IIIS and its physiological function, as well as the pro-inflammatory effects observed in COVID-19 and other pathological conditions and treatments. The authors discuss how the IIIS, comprising plasma proteins and blood cells, contributes to the acute innate immune response and its implications in modern medicine.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Hajar El Filaly, Meryem Mabrouk, Farah Atifi, Fadila Guessous, Khadija Akarid, Yahye Merhi, Younes Zaid
Summary: Platelets play a crucial role in primary hemostasis and pathological inflammation-induced thrombosis. Recent studies have expanded the understanding of platelets, placing them within the immune continuum and highlighting their involvement in both innate and adaptive immune responses. Platelets express Toll-Like Receptors (TLRs), which are key receptors in the inflammatory cell-cell reaction and the interaction between innate and adaptive immunity. This review focuses on the role of platelets in modulating platelet count and adaptive immune response during viral infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Matteo Grioni, Arianna Brevi, Elena Cattaneo, Alessandra Rovida, Jessica Bordini, Maria Teresa Sabrina Bertilaccio, Maurilio Ponzoni, Giulia Casorati, Paolo Dellabona, Paolo Ghia, Matteo Bellone, Arianna Calcinotto
Summary: The presence of CD4(+) T cells is essential for the development of chronic lymphocytic leukemia (CLL), while CD8(+) T cells have an antitumor effect in restraining CLL progression. Antigen specificity of CD4(+) T cells has marginal impact on CLL development.
Article
Cell Biology
Anna L. Gray, Richard Karlsson, Abigail R. E. Roberts, Amanda J. L. Ridley, Nabina Pun, Bakhtbilland Khan, Craig Lawless, Rafael Luis, Martyna Szpakowska, Andy Chevigne, Catherine E. Hughes, Laura Medina-Ruiz, Holly L. Birchenough, Iashia Z. Mulholland, Catherina L. Salanga, Edwin A. Yates, Jeremy E. Turnbull, Tracy M. Handel, Gerard J. Graham, Thomas A. Jowitt, Ingo Schiessl, Ralf P. Richter, Rebecca L. Miller, Douglas P. Dyer
Summary: Leukocyte recruitment from the vasculature into tissues plays a crucial role in the immune system and inflammatory diseases. However, the mechanisms underlying this process, particularly the function of CXCL4, have not been well understood. In this study, we demonstrate that CXCL4 binds to glycosaminoglycan (GAG) sugars on proteoglycans in the endothelial extracellular matrix, leading to increased leukocyte adhesion, vascular permeability, and non-specific recruitment of various leukocytes. This research provides mechanistic insights into chemokine biology and offers potential therapeutic targets.
Article
Immunology
Laura Naranjo, Ljudmila Stojanovich, Aleksandra Djokovic, Laura Andreoli, Angela Tincani, Maria Mslinska, Savino Sciascia, Maria Infantino, Sara Garcinuno, Kinga Kostyra-Grabczak, Mariangela Manfredi, Francesca Regola, Natasa Stanisavljevic, Milomir Milanovic, Jovica Saponjski, Dario Roccatello, Irene Cecchi, Massimo Radin, Maurizio Benucci, Daniel Pleguezuelo, Manuel Serrano, Yehuda Shoenfeld, Antonio Serrano
Summary: The aim of this multicenter, cross-sectional and observational study was to evaluate the association between the presence of circulating immune complexes (CIC) formed by beta-2-glycoprotein-I (B2GP1) and anti-B2GP1 antibodies (B2-CIC) and clinical manifestations in patients with antiphospholipid syndrome (APS). The results showed that patients with thrombotic events and positive for B2-CIC had lower platelet count and complement levels, suggesting a greater degree of platelet activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Julian Schlueter, Sarah Cunningham, Robert Zimmermann, Susanne Achenbach, Rafaela Kramer, Michael Erdmann, Malte Beckmann, Lucie Heinzerling, Holger Hackstein
Summary: Immune checkpoint inhibitors (ICIs) are effective oncological drugs that block cellular check-point receptors targeted by tumor immune evasion strategies. However, the direct effect of ICIs on platelet functionality and the influence of altered T cell function on platelet activation in the development of thrombotic events remain unclear. In vitro experiments showed no clear effect of ICIs on platelet aggregation and primary hemostasis, and the presence of ICIs had no significant impact on platelet surface marker expression. The data suggest that the direct influence of ICIs on platelet activation and the influence of altered T cell function on platelet activation are not major factors in the development of thrombotic events.
Article
Hematology
Andreas Greinacher, Florian Langer, Mike Makris, Menaka Pai, Sue Pavord, Huyen Tran, Theodore E. Warkentin
Summary: VITT is a rare but severe immunological reaction to non-replicable adenoviral vector-based COVID-19 vaccines, causing extreme activation of platelets and the coagulation system, increasing the risk of death. The World Health Organization provided guidelines for the diagnosis and management of VITT, and authors summarized new clinically relevant information with recommendations for low resource environments.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Rheumatology
Manuel Serrano, Gerard Espinosa, Antonio Lalueza, Luz Yadira Bravo-Gallego, Raquel Diaz-Simon, Sara Garcinuno, Javier Gil-Etayo, Jorge Moises, Laura Naranjo, Sergio Prieto-Gonzalez, Estibaliz Ruiz-Ortiz, Beatriz Sanchez, Ana Belen Moreno-Castano, Carmen Diaz-Pedroche, Odette Vinas-Gomis, Ricard Cervera, Antonio Serrano
Summary: The prevalence of aPLs, including classic aPLs and IgA-a beta 2GPI, is high in patients with COVID-19, but is not significantly associated with clinical outcomes. Low beta 2GPI levels are associated with ventilatory failure.
ACR OPEN RHEUMATOLOGY
(2021)
Article
Pathology
Maximilian Ackermann, Christopher Werlein, Florian Laenger, Mark P. Kuehnel, Danny D. Jonigk
Summary: Viral respiratory diseases are the most common reasons for hospitalization globally, with COVID-19 causing progressive respiratory failure and pronounced diffuse alveolar damage as a primary cause of death. COVID-19 pneumonia shares common histopathological features with influenza-related ARDS, such as diffuse alveolar damage and abnormal blood vessel neoformation. The lungs of COVID-19 patients display perivascular inflammation, endothelial injury, microangiopathy, and aberrant blood vessel formation through intussusceptive angiogenesis.
Article
Oncology
Dennis Strassmann, Bennet Hensen, Viktor Gruenwald, Katharina Stange, Hendrik Eggers, Florian Laenger, Mohamed Omar, Patrick Zardo, Hans Christiansen, Christoph W. Reuter, Frank K. Wacker, Arnold Ganser, Philipp Ivanyi
Summary: This retrospective study focused on the prognostic impact of sarcopenia on a/mSTS patients, revealing that sarcopenic patients were older, received less treatment, and had lower overall survival rates. Sarcopenia was identified as an independent prognostic parameter affecting overall survival.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2021)
Correction
Pathology
Korinna Joehrens, Gustavo Baretton, Hans-Ulrich Schildhaus, Abbas Agaimy, Andreas Scheel, Kristina Schwammborn, Florian Laenger, Markus Tiemann, Manfred Dietel
Article
Pediatrics
Florian Gothe, Jonathan Gehrig, Christina K. Rapp, Katrin Knoflach, Simone Reu-Hofer, Florian Langer, Dirk Schramm, Julia Ley-Zaporozhan, Stephan Ehl, Nicolaus Schwerk, Laura Faletti, Matthias Griese
Summary: This study reports three individuals with de novo STAT3 GOF alleles and early-onset, severe interstitial lung disease. Imaging and histology revealed fibrotic and cystic tissue destruction in the lung. The definitive diagnosis was established by postmortem whole exome sequencing and functional validation of new STAT3 variants.
PEDIATRIC PULMONOLOGY
(2021)
Article
Critical Care Medicine
Maximilian Ackermann, Paul Tafforeau, Willi L. Wagner, Claire L. Walsh, Christopher Werlein, Mark P. Kuehnel, Florian P. Laenger, Catherine Disney, Andrew J. Bodey, Alexandre Bellier, Stijn E. Verleden, Peter D. Lee, Steven J. Mentzer, Danny D. Jonigk
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jan C. Kamp, Lavinia Neubert, Maximilian Ackermann, Helge Stark, Christopher Werlein, Jan Fuge, Axel Haverich, Alexandar Tzankov, Konrad Steinestel, Johannes Friemann, Peter Boor, Klaus Junker, Marius M. Hoeper, Tobias Welte, Florian Laenger, Mark P. Kuehnel, Danny D. Jonigk
Summary: There is an increased prevalence of pulmonary fibrosis in COVID-19 survivors, but the underlying molecular mechanisms are not well understood. This multicentric study found that there is a shift from pro-inflammatory to fibrogenic activity after the first week of hospitalization in severe COVID-19.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Rosemary Poulose, Anselm A. Derda, Mohamed Omar, Christian von Falck, Florian Laenger, Jochen Tillmanns, Adrian Groh, Johann Bauersachs, L. Christian Napp
Summary: This report describes a patient with deep vein thrombosis of the right leg, who was found to have an unknown chondrosarcoma of the tibia. The physical examination revealed a firm, nondisplaceable mass on the dorsal side of the right knee, which appeared as a cystic formation on ultrasound. Imaging studies confirmed the diagnosis of chondrosarcoma, which likely caused the thrombosis through local compression or paraneoplastic mechanisms. After tumor resection, anticoagulation therapy was continued. A final diagnosis of highly differentiated chondrosarcoma with thrombosis of the popliteal vein was made based on all findings.
Editorial Material
Pediatrics
Inga Thiemann, Thomas Hoppen, Martin Laur, Manuel Ohlert, Stephan Lobitz, Nicolaus Schwerk, Jens Dingemann, Florian Laenger, Ruth Margarethe Grychtol, Thomas Nusslein
Summary: Complete tracheal ring deformity (CTRD) is a rare abnormality characterized by continuous cartilaginous tracheal rings, leading to variable degrees of tracheal stenosis. Pleuropulmonary blastomas (PPB) are malignant tumors that occur mainly in young children. Pathogenic DICER1 variants are associated with PPB and other tumors or syndromic diseases.
KLINISCHE PADIATRIE
(2022)
Article
Cell Biology
Jan C. Kamp, Lavinia Neubert, Helge Stark, Jan B. Hinrichs, Caja Boekhoff, Allison D. Seidel, Fabio Ius, Axel Haverich, Jens Gottlieb, Tobias Welte, Peter Braubach, Florian Laenger, Marius M. Hoeper, Mark P. Kuehnel, Danny D. Jonigk
Summary: This study analyzed the gene expression profiles of fibroblastic foci (FF) in idiopathic pulmonary fibrosis (IPF) and sarcoidosis, and found that they have similar gene and protein expression. However, there are differences in the initiation of FF between the two diseases. These results have important implications for the use of antifibrotic agents in sarcoidosis.
Article
Pathology
Matthias Christgen, Leonie Donata Kandt, Wiebke Antonopoulos, Stephan Bartels, Mieke R. Van Bockstal, Martin Bredt, Maria Jose Brito, Henriette Christgen, Cecile Colpaert, Balint Cserni, Gabor Cserni, Maximilian E. Daemmrich, Raihanatou Danebrock, Franceska Dedeurwaerdere, Carolien H. M. van Deurzen, Ramona Erber, Christine Fathke, Henning Feist, Maryse Fiche, Claudia Aura Gonzalez, Natalie D. ter Hoeve, Loes Kooreman, Till Krech, Glen Kristiansen, Janina Kulka, Florian Laenger, Marcel Lafos, Ulrich Lehmann, Maria Dolores Martin-Martinez, Sophie Mueller, Enrico Pelz, Mieke Raap, Alberto Ravarino, Tanja Reineke-Plaass, Nora Schaumann, Anne-Marie Schelfhout, Maxim De Schepper, Jerome Schlue, Koen Van de Vijver, Wim Waelput, Axel Wellmann, Monika Graeser, Oleg Gluz, Sherko Kuemmel, Ulrike Nitz, Nadia Harbeck, Christine Desmedt, Giuseppe Floris, Patrick W. B. Derksen, Paul J. van Diest, Anne Vincent-Salomon, Hans Kreipe
Summary: Subtyping of breast cancer as ILC achieves almost perfect agreement with a pre-defined reference standard if supported by E-cadherin IHC. CDH1 missense mutations, E- to P-cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Bennet Hensen, Urte Drenkmann, Bernd Frericks, Eva Rothgang, Marcel Gutberlet, Florian Laenger, Wesley Gilson, Steffi Valdeig, Clifford R. Weiss, Frank Wacker
Summary: This study aimed to determine the best magnetic resonance (MR) sequences for assessing ablation zones after radiofrequency ablation (RFA). The results showed that post-contrast T1 3DTFL sequence performed the best in evaluating the ablation zones.
CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
(2022)
Editorial Material
Oncology
Nikolaj Frost, Frank Griesinger, Hans Hoffmann, Florian Laenger, Ursula Nestle, Wolfgang Schuette, Juergen Wolf, Martin Reck
JOURNAL OF THORACIC ONCOLOGY
(2022)
Article
Respiratory System
Florian Peter Laenger, Nicolaus Schwerk, Jens Dingemann, Tobias Welte, Bernd Auber, Stijn Verleden, Maximilian Ackermann, Steven J. Mentzer, Matthias Griese, Danny Jonigk
Summary: Children's interstitial lung disease (chILD) is a wide and heterogeneous group of diseases that is substantially different from adult lung diseases. It is categorized into diseases more common in infancy and diseases that can occur at any age based on clinical, radiological, genetic, and histological findings. Lung biopsies may be considered for diagnostic evaluation if other approaches failed to identify a specific chILD entity or if there is severe or refractory respiratory distress of unknown cause. This review summarizes relevant clinical, genetic, and histological findings of chILD to assist in clinical assessment and rational diagnostics, particularly for children evaluated and diagnosed outside of specialist centers.
EUROPEAN RESPIRATORY REVIEW
(2022)
Article
Medicine, General & Internal
Stijn E. Verleden, Peter Braubach, Christopher Werlein, Edith Plucinski, Mark P. Kuhnel, Annemiek Snoeckx, Haroun El Addouli, Tobias Welte, Axel Haverich, Florian P. Laenger, Sabine Dettmer, Patrick Pauwels, Veronique Verplancke, Paul E. Van Schil, Therese Lapperre, Johanna M. Kwakkel-Van-Erp, Maximilian Ackermann, Jeroen M. H. Hendriks, Danny Jonigk
Summary: Pathology and radiology are complementary tools in diagnosing non-neoplastic pulmonary diseases. The innovative technique of inflating whole lung specimens and subjecting them to CT allows for an accurate matching of CT imaging and histopathology data. This technique enables targeted assessment of localized disease extent and investigation of early mechanisms of lung diseases on a morphological and molecular level.
FRONTIERS IN MEDICINE
(2022)
Article
Respiratory System
Julia Carlens, K. Taneille Johnson, Andrew Bush, Diane Renz, Ute Hehr, Florian Laenger, Claire Hogg, Martin Wetzke, Nicolaus Schwerk, Jonathan H. Rayment
Summary: This study aimed to further understand the long-term respiratory outcomes in children's interstitial lung disease associated with FLNA variants. The researchers analyzed clinical, radiographic, and histopathologic data from nine cases and found that early mortality was common, but many survivors stabilized even after severe symptoms in infancy. All survivors had persistent obstructive defects on spirometry, and half have persistent or recurrent pulmonary hypertension. These findings suggest the importance of genetic testing for this rare diagnosis.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2022)