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JOURNAL ARTICLE
Maria Elena Maccari, Sebastian Fuchs, Patrick Kury, Geoffroy Andrieux, Simon Völkl, Bertram Bengsch, Myriam Ricarda Lorenz, Maximilian Heeg, Jan Rohr, Sabine Jägle, Carla N Castro, Miriam Groß, Ursula Warthorst, Christoph König, Ilka Fuchs, Carsten Speckmann, Julian Thalhammer, Friedrich G Kapp, Markus G Seidel, Gregor Dückers, Stefan Schönberger, Catharina Schütz, Marita Führer, Robin Kobbe, Dirk Holzinger, Christian Klemann, Petr Smisek, Stephen Owens, Gerd Horneff, Reinhard Kolb, Nora Naumann-Bartsch, Maurizio Miano, Julian Staniek, Marta Rizzi, Tomas Kalina, Pascal Schneider, Anika Erxleben, Rolf Backofen, Arif Ekici, Charlotte M Niemeyer, Klaus Warnatz, Bodo Grimbacher, Hermann Eibel, Andreas Mackensen, Andreas Philipp Frei, Klaus Schwarz, Melanie Boerries, Stephan Ehl, Anne Rensing-Ehl
The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαβ+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection...
February 1, 2021: Journal of Experimental Medicine
#22
JOURNAL ARTICLE
Sujal Ghosh, Sevgi Köstel Bal, Emily S J Edwards, Bethany Pillay, Raúl Jimenez-Heredia, Geetha Rao, Funda Erol Cipe, Elisabeth Salzer, Samaneh Zoghi, Hassan Abolhassani, Tooba Momen, Emma Gostick, David A Price, Yu Zhang, Andrew J Oler, Claudia Gonzaga-Jauregui, Baran Erman, Ayse Metin, Inci Ilhan, Sule Haskologlu, Candan Islamoglu, Kubra Baskin, Serdar Ceylaner, Ebru Yilmaz, Ekrem Unal, Musa Karakukcu, Dagmar Berghuis, Theresa Cole, Aditya Kumar Gupta, Fabian Hauck, Andy Hoepelman, Safa Baris, Elif Karakoc-Aydiner, Ahmet Ozen, Leo Kager, Dirk Holzinger, Michael Paulussen, Renate Krüger, Roland Meisel, Prasad Thomas Oommen, Emma C Morris, Benedicte Neven, Austen J J Worth, Joris M van Montfrans, Pieter Fraaij, Sharon Choo, Figen Dogu, E Graham Davies, Siobhan Burns, Gregor Dueckers, Ruy Perez Becker, Horst von Bernuth, Sylvain Latour, Maura Faraci, Marco Gattorno, Helen Su, Qiang Pan-Hammarström, Lennart Hammarström, Michael J Lenardo, Cindy S Ma, Tim Niehues, Asghar Aghamohammadi, Nima Rezaei, Aydan Ikinciogullari, Stuart G Tangye, Arjan C Lankester, Kaan Boztug
Biallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity characterized predominantly by EBV-associated immune dysregulation, such as chronic viremia, severe infectious mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoproliferation and malignancy. A comprehensive understanding of the natural history, immune characteristics and transplant outcomes has remained elusive. Here, in a multi-institutional global collaboration, we collected clinical information of 49 patients from 29 families (CD27 n=33, CD70 n=16), including 24 previously unreported individuals and identified a total of 16 distinct mutations in CD27, and 8 in CD70, respectively...
June 30, 2020: Blood
#23
JOURNAL ARTICLE
Jan Rekowski, Andreas Hüttmann, Christine Schmitz, Stefan P Müller, Lars Kurch, Jörg Kotzerke, Christiane Franzius, Matthias Weckesser, Frank M Bengel, Martin Freesmeyer, Andreas Hertel, Thomas Krohn, Jens Holzinger, Ingo Brink, Uwe Haberkorn, Fonyuy Nyuyki, Daniëlle M E van Assema, Lilli Geworski, Dirk Hasenclever, Karl-Heinz Jöckel, Ulrich Dührsen
The value of interim 18 F-fluorodeoxyglucose positron emission tomography (iPET) guided treatment decisions in patients with diffuse large B-cell lymphoma (DLBCL) has been the subject of much debate. This investigation focuses on a comparison of the Deauville score and the deltaSUVmax (ΔSUVmax ) approach - two methods to assess early metabolic response to standard chemotherapy in DLBCL. Methods: Of 609 DLBCL patients participating in the Positron Emission Tomography-guided Therapy of Aggressive non-Hodgkin Lymphomas (PETAL) trial, iPET scans of 596 patients originally evaluated using the ΔSUVmax method were available for post-hoc assessment of the Deauville score...
May 8, 2020: Journal of Nuclear Medicine
#24
JOURNAL ARTICLE
Tiziana Lorenzini, Manfred Fliegauf, Nils Klammer, Natalie Frede, Michele Proietti, Alla Bulashevska, Nadezhda Camacho-Ordonez, Markku Varjosalo, Matias Kinnunen, Esther de Vries, Jos W M van der Meer, Rohan Ameratunga, Chaim M Roifman, Yael D Schejter, Robin Kobbe, Timo Hautala, Faranaz Atschekzei, Reinhold E Schmidt, Claudia Schröder, Polina Stepensky, Bella Shadur, Luis A Pedroza, Michiel van der Flier, Mónica Martínez-Gallo, Luis Ignacio Gonzalez-Granado, Luis M Allende, Anna Shcherbina, Natalia Kuzmenko, Victoria Zakharova, João Farela Neves, Peter Svec, Ute Fischer, Winnie Ip, Oliver Bartsch, Safa Barış, Christoph Klein, Raif Geha, Janet Chou, Mohammed Alosaimi, Lauren Weintraub, Kaan Boztug, Tatjana Hirschmugl, Maria Marluce Dos Santos Vilela, Dirk Holzinger, Maximilian Seidl, Vassilios Lougaris, Alessandro Plebani, Laia Alsina, Monica Piquer-Gibert, Angela Deyà-Martínez, Charlotte A Slade, Asghar Aghamohammadi, Hassan Abolhassani, Lennart Hammarström, Outi Kuismin, Merja Helminen, Hana Lango Allen, James E Thaventhiran, Alexandra F Freeman, Matthew Cook, Shahrzad Bakhtiar, Mette Christiansen, Charlotte Cunningham-Rundles, Niraj C Patel, William Rae, Tim Niehues, Nina Brauer, Jaana Syrjänen, Mikko R J Seppänen, Siobhan O Burns, Paul Tuijnenburg, Taco W Kuijpers, Klaus Warnatz, Bodo Grimbacher
BACKGROUND: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. OBJECTIVE: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. METHODS: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling...
October 2020: Journal of Allergy and Clinical Immunology
#25
JOURNAL ARTICLE
CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow.
Lena Fischer-Riepe, Niklas Daber, Jonas Schulte-Schrepping, Bruna Caroline Véras De Carvalho, Antonella Russo, Michele Pohlen, Josephine Fischer, Achmet Imam Chasan, Marc Wolf, Thomas Ulas, Shirin Glander, Christian Schulz, Boris Skryabin, Andreas Wollbrink, Nadine Steingraeber, Christopher Stremmel, Megan Koehle, Florian Gärtner, Sabine Vettorazzi, Dirk Holzinger, Joachim Gross, Frank Rosenbauer, Monika Stoll, Silke Niemann, Jan Tuckermann, Joachim L Schultze, Johannes Roth, Katarzyna Barczyk-Kahlert
BACKGROUND: Scavenger receptor CD163 is exclusively expressed on monocytes/macrophages and is widely used as a marker for alternatively activated macrophages. However, the role of CD163 is not yet clear. OBJECTIVES: We examined the function of CD163 in steady-state as well as in sterile and infectious inflammation. METHODS: Expression of CD163 was analyzed under normal and inflammatory conditions in mice. Functional relevance of CD163 was investigated in models of inflammation in wildtype and CD163-/- mice...
March 18, 2020: Journal of Allergy and Clinical Immunology
#26
JOURNAL ARTICLE
Sandra Hansmann, Elke Lainka, Gerd Horneff, Dirk Holzinger, Nikolaus Rieber, Annette F Jansson, Angela Rösen-Wolff, Gabi Erbis, Martina Prelog, Juergen Brunner, Susanne M Benseler, Jasmin B Kuemmerle-Deschner
BACKGROUND: Rare autoinflammatory diseases (AIDs) including Cryopyrin-Associated Periodic Syndrome (CAPS), Tumor Necrosis Receptor-Associated Periodic Syndrome (TRAPS) and Mevalonate Kinase Deficiency Syndrome (MKD)/ Hyper-IgD Syndrome (HIDS) are genetically defined and characterized by recurrent fever episodes and inflammatory organ manifestations. Early diagnosis and early start of effective therapies control the inflammation and prevent organ damage. The PRO-KIND initiative of the German Society of Pediatric Rheumatology (GKJR) aims to harmonize the diagnosis and management of children with rheumatic diseases nationally...
February 17, 2020: Pediatric Rheumatology Online Journal
#27
JOURNAL ARTICLE
Emely Verweyen, Dirk Holzinger, Toni Weinhage, Claas Hinze, Helmut Wittkowski, Peter Pickkers, Sabrin Albeituni, Katherine Verbist, Kim E Nichols, Grant Schulert, Alexei Grom, Dirk Foell, Christoph Kessel
Rationale: IL-18 is a member of the IL-1 cytokine family, and elevated blood IL-18 concentrations associate with disease activity in macrophage activation syndrome (MAS) and poor clinical outcomes in severe inflammatory and septic conditions. Objectives: Although recent investigations provide mechanistic evidence for a contribution of IL-18 to inflammation and hyperinflammation in sepsis and MAS, we sought to study regulatory mechanisms underlying human IL-18 expression. Methods: Samples from in vivo and in vitro endotoxin rechallenge experiments, patients with inflammatory disease, and isolated human monocytes treated with various stimulants and drugs were tested for cytokine gene and protein expression...
March 1, 2020: American Journal of Respiratory and Critical Care Medicine
#28
JOURNAL ARTICLE
Simon Laban, Dominik S Gangkofner, Dana Holzinger, Lea Schroeder, Stefan B Eichmüller, Inka Zörnig, Dirk Jäger, Gunnar Wichmann, Andreas Dietz, Martina A Broglie, Christel C Herold-Mende, Gerhard Dyckhoff, Paolo Boscolo-Rizzo, Jasmin Ezić, Ralf Marienfeld, Peter Möller, Johann M Kraus, Gunnar Völkel, Hans A Kestler, Cornelia Brunner, Patrick J Schuler, Marlene C Wigand, Marie-Nicole Theodoraki, Johannes Doescher, Thomas K Hoffmann, Michael Pawlita, Tim Waterboer, Julia Butt
PURPOSE: The identification of high-risk patients within Human Papillomavirus (HPV) positive and negative head and neck squamous cell carcinoma patients is needed for improved treatment and surveillance strategies. In this study, we set out to discover Antibody responses (AR) with prognostic impact in head and neck squamous cell carcinoma (HNSCC) stratified by HPV-status. EXPERIMENTAL DESIGN: A fluorescent bead-based multiplex serology assay to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens, 8 oncogenes) and 29 HPV-antigens was performed in samples of 362 HNSCC patients from five independent cohorts (153 HPV-positive, 209 HPV-negative)...
August 23, 2019: Clinical Cancer Research
#29
JOURNAL ARTICLE
Dominik S Gangkofner, Dana Holzinger, Lea Schroeder, Stefan B Eichmüller, Inka Zörnig, Dirk Jäger, Gunnar Wichmann, Andreas Dietz, Martina A Broglie, Christel Herold-Mende, Gerhard Dyckhoff, Paolo Boscolo-Rizzo, Jasmin Ezic, Ralf B Marienfeld, Peter Möller, Gunnar Völkel, Johann M Kraus, Hans A Kestler, Cornelia Brunner, Patrick J Schuler, Marlene Wigand, Marie N Theodoraki, Johannes Doescher, Thomas K Hoffmann, Michael Pawlita, Julia Butt, Tim Waterboer, Simon Laban
There have been hints that non-viral cancer antigens are differentially expressed in Human Papillomavirus (HPV) positive and HPV-negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a non-invasive and tissue-saving liquid biopsy. Here, we set out to characterize AR to a panel of non-viral cancer antigens in HPV-positive and HPV-negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens, 8 oncogenes) and 29 HPV-antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV-positive, 209 HPV-negative)...
August 12, 2019: International Journal of Cancer. Journal International du Cancer
#30
COMPARATIVE STUDY
Faekah Gohar, Angela McArdle, Melissa Jones, Niamh Callan, Belinda Hernandez, Christoph Kessel, Maria Miranda-Garcia, Miha Lavric, Dirk Holzinger, Carolin Pretzer, Elke Lainka, Sebastiaan J Vastert, Sytze de Roock, Oliver FitzGerald, Stephen R Pennington, Dirk Foell
OBJECTIVES: The International League of Associations for Rheumatology classification criteria define systemic juvenile idiopathic arthritis (SJIA) by the presence of fever, rash and chronic arthritis. Recent initiatives to revise current criteria recognise that a lack of arthritis complicates making the diagnosis early, while later a subgroup of patients develops aggressive joint disease. The proposed biphasic model of SJIA also implies a 'window of opportunity' to abrogate the development of chronic arthritis...
August 2019: Annals of the Rheumatic Diseases
#31
JOURNAL ARTICLE
Nienke M Ter Haar, E H Pieter van Dijkhuizen, Joost F Swart, Annet van Royen-Kerkhof, Ayman El Idrissi, Arjen P Leek, Wilco de Jager, Mark C H de Groot, Saskia Haitjema, Dirk Holzinger, Dirk Foell, Jorg van Loosdregt, Nico M Wulffraat, Sytze de Roock, Sebastiaan J Vastert
OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) is a multifactorial autoinflammatory disease with a historically poor prognosis. With current treatment regimens, approximately half of patients still experience active disease after 1 year of therapy. This study was undertaken to evaluate a treat-to-target approach using recombinant interleukin-1 receptor antagonist (rIL-1Ra; anakinra) as first-line monotherapy to achieve early inactive disease and prevent damage. METHODS: In this single-center, prospective study, patients with new-onset systemic JIA with an unsatisfactory response to nonsteroidal antiinflammatory drugs received rIL-1Ra monotherapy according to a treat-to-target strategy...
July 2019: Arthritis & Rheumatology
#32
REVIEW
Dirk Holzinger, Dirk Foell, Christoph Kessel
S100A8/A9 and S100A12 are released from activated monocytes and granulocytes and act as proinflammatory endogenous toll-like receptor (TLR)4-ligands. S100 serum concentrations correlate with disease activity, both during local and systemic inflammatory processes. In some autoinflammatory diseases such as familial Mediterranean fever (FMF) or systemic juvenile idiopathic arthritis (SJIA), dysregulation of S100 release may be involved in the pathogenesis. Moreover, S100 serum levels are a valuable supportive tool in the diagnosis of SJIA in fever of unknown origin...
September 25, 2018: Molecular and Cellular Pediatrics
#33
JOURNAL ARTICLE
Christoph Kessel, Sabrina Fuehner, Jana Zell, Bastian Zimmermann, Stephan Drewianka, Sonja Brockmeyer, Dirk Holzinger, Claas Hinze, Helmut Wittkowski, Dirk Foell
No abstract text is available yet for this article.
July 3, 2018: Journal of Allergy and Clinical Immunology
#34
RANDOMIZED CONTROLLED TRIAL
Ulrich Dührsen, Stefan Müller, Bernd Hertenstein, Henrike Thomssen, Jörg Kotzerke, Rolf Mesters, Wolfgang E Berdel, Christiane Franzius, Frank Kroschinsky, Matthias Weckesser, Dorothea Kofahl-Krause, Frank M Bengel, Jan Dürig, Johannes Matschke, Christine Schmitz, Thorsten Pöppel, Claudia Ose, Marcus Brinkmann, Paul La Rosée, Martin Freesmeyer, Andreas Hertel, Heinz-Gert Höffkes, Dirk Behringer, Gabriele Prange-Krex, Stefan Wilop, Thomas Krohn, Jens Holzinger, Martin Griesshammer, Aristoteles Giagounidis, Aruna Raghavachar, Georg Maschmeyer, Ingo Brink, Helga Bernhard, Uwe Haberkorn, Tobias Gaska, Lars Kurch, Daniëlle M E van Assema, Wolfram Klapper, Dieter Hoelzer, Lilli Geworski, Karl-Heinz Jöckel, André Scherag, Andreas Bockisch, Jan Rekowski, Andreas Hüttmann
Purpose Interim positron emission tomography (PET) using the tracer, [18 F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP-plus rituximab (R-CHOP) in CD20-positive lymphomas-followed by a PET scan that was evaluated using the ΔSUVmax method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt's lymphoma protocol...
July 10, 2018: Journal of Clinical Oncology
#35
JOURNAL ARTICLE
Jason Michael Springer, Paul Monach, David Cuthbertson, Simon Carette, Nader A Khalidi, Carol A McAlear, Christian Pagnoux, Philip Seo, Kenneth J Warrington, Steven R Ytterberg, Gary Hoffman, Carol Langford, Thomas Hamilton, Dirk Foell, Thomas Vogl, Dirk Holzinger, Peter A Merkel, Johannes Roth, Rula A Hajj-Ali
No abstract text is available yet for this article.
October 2018: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
#36
JOURNAL ARTICLE
Silke Niemann, Anne Bertling, Martin F Brodde, Anke C Fender, Hélène Van de Vyver, Muzaffar Hussain, Dirk Holzinger, Dirk Reinhardt, Georg Peters, Christine Heilmann, Bettina Löffler, Beate E Kehrel
Globalization and migration promote the spread of Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus strains. The toxin PVL is linked to the development of thrombosis in association with osteomyelitis. The mechanisms by which PVL drives thrombosis development are however still unknown. We demonstrate that PVL-damaged neutrophils activate platelets via neutrophil secretion products, such as α-defensins and the myeloperoxidase product HOCl, as well as the formation of HOCl-modified proteins. Neutrophil damage by PVL is blocked by anti-PVL-antibodies, explaining why especially young osteomyelitis patients with a low antibody titre against PVL suffer from thrombotic complications...
February 1, 2018: Scientific Reports
#37
JOURNAL ARTICLE
Claas H Hinze, Dirk Holzinger, Elke Lainka, Johannes-Peter Haas, Fabian Speth, Tilmann Kallinich, Nikolaus Rieber, Markus Hufnagel, Annette F Jansson, Christian Hedrich, Hanna Winowski, Thomas Berger, Ivan Foeldvari, Gerd Ganser, Anton Hospach, Hans-Iko Huppertz, Kirsten Mönkemöller, Ulrich Neudorf, Elisabeth Weißbarth-Riedel, Helmut Wittkowski, Gerd Horneff, Dirk Foell
BACKGROUND: Systemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory disease associated with chronic arthritis. Early diagnosis and effective therapy of SJIA is desirable, so that complications are avoided. The PRO-KIND initiative of the German Society for Pediatric Rheumatology (GKJR) aims to define consensus-based strategies to harmonize diagnostic and therapeutic approaches in Germany. METHODS: We analyzed data on patients diagnosed with SJIA from 3 national registries in Germany...
January 22, 2018: Pediatric Rheumatology Online Journal
#38
JOURNAL ARTICLE
Faekah Gohar, Janneke Anink, Halima Moncrieffe, Lisette W A Van Suijlekom-Smit, Femke H M Prince, Marion A J van Rossum, Koert M Dolman, Esther P A H Hoppenreijs, Rebecca Ten Cate, Simona Ursu, Lucy R Wedderburn, Gerd Horneff, Michael Frosch, Dirk Foell, Dirk Holzinger
OBJECTIVE: Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response...
April 2018: Journal of Rheumatology
#39
JOURNAL ARTICLE
Eric S Weiss, Charlotte Girard-Guyonvarc'h, Dirk Holzinger, Adriana A de Jesus, Zeshan Tariq, Jennifer Picarsic, Eduardo J Schiffrin, Dirk Foell, Alexei A Grom, Sandra Ammann, Stephan Ehl, Tomoaki Hoshino, Raphaela Goldbach-Mansky, Cem Gabay, Scott W Canna
Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperferritinemic systemic inflammatory disorders. Although profound cytotoxic impairment causes familial HLH (fHLH), the mechanisms driving non-fHLH and MAS are largely unknown. MAS occurs in patients with suspected rheumatic disease, but the mechanistic basis for its distinction is unclear. Recently, a syndrome of recurrent MAS with infantile enterocolitis caused by NLRC4 inflammasome hyperactivity highlighted the potential importance of interleukin-18 (IL-18)...
March 29, 2018: Blood
#40
JOURNAL ARTICLE
Karoline Walscheid, Lisa Neekamp, Arnd Heiligenhaus, Toni Weinhage, Dirk Holzinger, Carsten Heinz, Maren Kasper, Dirk Foell
OBJECTIVE: To characterize peripheral blood monocytes in uveitis associated with juvenile idiopathic arthritis (JIAU). METHODS: Peripheral blood monocytes from children with JIA (either with (n = 18) or without uveitis (n = 11)), idiopathic anterior uveitis (IAU; n = 12) and healthy controls (n = 11) were analyzed by flow cytometry. RESULTS: Percentage of CD14 + CD86+ monocytes and CD86 expression on single cell level were significantly higher in all patient groups than in controls, whereas no major differences existed between patient groups...
May 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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