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Fiebiger, Edda

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Fiebiger

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Edda

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Fiebiger, Edda

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2007 - 200912010 - 20169

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Author's Publications: search.filters.isAuthorOfPublication.d71c3444-6607-49ab-9dfb-1829a38c6b63

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    A single glycan on IgE is indispensable for initiation of anaphylaxis
    (The Rockefeller University Press, 2015) Shade, Kai-Ting C.; Platzer, Barbara; Washburn, Nathaniel; Mani, Vinidhra; Bartsch, Yannic C.; Conroy, Michelle; Pagan, Jose D.; Bosques, Carlos; Mempel, Thorsten; Fiebiger, Edda; Anthony, Robert
    Immunoglobulin ε (IgE) antibodies are the primary mediators of allergic diseases, which affect more than 1 in 10 individuals worldwide. IgE specific for innocuous environmental antigens, or allergens, binds and sensitizes tissue-resident mast cells expressing the high-affinity IgE receptor, FcεRI. Subsequent allergen exposure cross-links mast cell–bound IgE, resulting in the release of inflammatory mediators and initiation of the allergic cascade. It is well established that precise glycosylation patterns exert profound effects on the biological activity of IgG. However, the contribution of glycosylation to IgE biology is less clear. Here, we demonstrate an absolute requirement for IgE glycosylation in allergic reactions. The obligatory glycan was mapped to a single N-linked oligomannose structure in the constant domain 3 (Cε3) of IgE, at asparagine-394 (N394) in human IgE and N384 in mouse. Genetic disruption of the site or enzymatic removal of the oligomannose glycan altered IgE secondary structure and abrogated IgE binding to FcεRI, rendering IgE incapable of eliciting mast cell degranulation, thereby preventing anaphylaxis. These results underscore an unappreciated and essential requirement of glycosylation in IgE biology.
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    Antigen Cross-Presentation of Immune Complexes
    (Frontiers Media S.A., 2014) Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda
    The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α+ DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8+ T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8− DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets.
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    Eosinophilic esophagitis: published evidences for disease subtypes, indications for patient subpopulations, and how to translate patient observations to murine experimental models
    (BioMed Central, 2016) Mudde, Anne C. A.; Lexmond, Willem S.; Blumberg, Richard; Nurko, Samuel; Fiebiger, Edda
    Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus and commonly classified as a Th2-type allergy. Major advances in our understanding of the EoE pathophysiology have recently been made, but clinicians struggle with highly unpredictable therapy responses indicative of phenotypic diversity within the patient population. Here, we summarize evidences for the existence of EoE subpopulations based on diverse inflammatory characteristics of the esophageal tissue in EoE. Additionally, clinical characteristics of EoE patients support the concept of disease subtypes. We conclude that clinical and experimental evidences indicate that EoE is an umbrella term for conditions that are unified by esophageal eosinophilia but that several disease subgroups with various inflammatory esophageal patterns and/or different clinical features exist. We further discuss strategies to study the pathophysiologic differences as observed in EoE patients in murine experimental EoE. Going forward, models of EoE that faithfully mimic EoE subentities as defined in humans will be essential because mechanistic studies on triggers which regulate the onset of diverse EoE subpopulations are not feasible in patients. Understanding how and why different EoE phenotypes develop will be a first and fundamental step to establish strategies that integrate individual variations of the EoE pathology into personalized therapy.
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    Electrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapy
    (Public Library of Science, 2015) Lexmond, Willem S.; Rufo, Paul; Fiebiger, Edda; Lencer, Wayne
    Background and Aims Morbidity and mortality from acute diarrheal disease remains high, particularly in developing countries and in cases of natural or man-made disasters. Previous work has shown that the small molecule clotrimazole inhibits intestinal Cl- secretion by blocking both cyclic nucleotide- and Ca2+-gated K+ channels, implicating its use in the treatment of diarrhea of diverse etiologies. Clotrimazole, however, might also inhibit transporters that mediate the inwardly directed electrochemical potential for Na+-dependent solute absorption, which would undermine its clinical application. Here we test this possibility by examining the effects of clotrimazole on Na+-coupled glucose uptake. Materials and Methods Short-circuit currents (Isc) following administration of glucose and secretagogues were studied in clotrimazole-treated jejunal sections of mouse intestine mounted in Ussing chambers. Results: Treatment of small intestinal tissue with clotrimazole inhibited the Cl- secretory currents that resulted from challenge with the cAMP-agonist vasoactive intestinal peptide (VIP) or Ca2+-agonist carbachol in a dose-dependent fashion. A dose of 30 μM was effective in significantly reducing the Isc response to VIP and carbachol by 50% and 72%, respectively. At this dose, uptake of glucose was only marginally affected (decreased by 14%, p = 0.37). There was no measurable effect on SGLT1-mediated sugar transport, as uptake of SGLT1-restricted 3-O-methyl glucose was equivalent between clotrimazole-treated and untreated tissue (98% vs. 100%, p = 0.90). Conclusion: Treatment of intestinal tissue with clotrimazole significantly reduced secretory responses caused by both cAMP- and Ca2+-dependent agonists as expected, but did not affect Na+-coupled glucose absorption. Clotrimazole could thus be used in conjunction with oral rehydration solution as a low-cost, auxiliary treatment of acute secretory diarrheas.
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    Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites
    (2014) Platzer, Barbara; Baker, Kristi; Vera, Miguel Pinilla; Singer, Kathleen; Panduro, Marisella; Lexmond, Willem S.; Turner, Devin; Vargas, Sara; Kinet, Jean-Pierre; Maurer, Dieter; Baron, Rebecca; Blumberg, Richard; Fiebiger, Edda
    Antigen-mediated crosslinking of Immunoglobulin E (IgE) bound to mast cells/basophils via FcεRI, the high affinity IgE Fc-receptor, is a well-known trigger of allergy. In humans, but not mice, dendritic cells (DCs) also express FcεRI that is constitutively occupied with IgE. In contrast to mast cells/basophils, the consequences of IgE/FcεRI signals for DC function remain poorly understood. We show that humanized mice that express FcεRI on DCs carry IgE like non-allergic humans and do not develop spontaneous allergies. Antigen-specific IgE/FcεRI crosslinking fails to induce maturation or production of inflammatory mediators in human DCs and FcεRI-humanized DCs. Furthermore, conferring expression of FcεRI to DCs decreases the severity of food allergy and asthma in disease-relevant models suggesting anti-inflammatory IgE/FcεRI signals. Consistent with the improved clinical parameters in vivo, antigen-specific IgE/FcεRI crosslinking on papain or LPS-stimulated DCs inhibits the production of pro-inflammatory cytokines and chemokines. Migration assays confirm that the IgE-dependent decrease in cytokine production results in diminished recruitment of mast cell progenitors; providing a mechanistic explanation for the reduced mast cell-dependent allergic phenotype observed in FcεRI-humanized mice. Our study demonstrates a novel immune regulatory function of IgE and proposes that DC-intrinsic IgE signals serve as a feedback mechanism to restrain allergic tissue inflammation.
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    EPMA-World Congress 2015: Bonn, Germany. 3-5 September 2015
    (BioMed Central, 2016) Abraham, Jella-Andrea; Golubnitschaja, Olga; Akhmetov, Ildar; Andrews, Russell J.; Quintana, Leonidas; Baban, Babak; Liu, Jun Yao; Qin, Xu; Wang, Tailing; Mozaffari, Mahmood S.; Bati, Viktoriia V.; Meleshko, Tamara V.; Levchuk, Olga B.; Boyko, Nadiya V.; Bauer, Joanna; Boerner, Ewa; Podbielska, Halina; Bomba, Alojz; Petrov, Viktor O.; Drobnych, Volodymyr G.; Bubnov, Rostyslav V.; Bykova, Oksana M.; Brunner-La Rocca, Hans-Peter; Fleischhacker, Lutz; Heemskerk, Frank; Helms, Thomas; Jaarsma, Tiny; Kinkorová, Judita; Ramaekers, Jan; Ruff, Peter; Schnur, Ivana; Vanoli, Emilio; Verdu, Jose; Grabovetskyi, Sergiy A.; Mykhalchenko, Olena M.; Tymoshok, Natalia O.; Shcherbakov, Oleksandr B.; Semeniv, Igor P.; Spivak, Mykola Y.; Ostapenko, Tetyana V.; Kobyliak, Nazarii M.; Zholobak, Nadiya M.; Spivak, Mykola Ya.; Cauchi, John Paul; Cherepakhin, Dmitrii; Bakay, Marina; Borovikov, Artem; Suchkov, Sergey; Cieślik, Barbara; Migasiewicz, Agnieszka; Podbielska, Maria-Luiza; Pelleter, Markus; Giemza, Agnieszka; Cirak, Sebahattin; Del Re, Marzia; Bordi, Paola; Citi, Valentina; Palombi, Marta; Pinto, Carmine; Tiseo, Marcello; Danesi, Romano; Einhorn, Lukas; Fazekas, Judit; Muhr, Martina; Schoos, Alexandra; Panakova, Lucia; Herrmann, Ina; Manzano-Szalai, Krisztina; Oida, Kumiko; Fiebiger, Edda; Singer, Josef; Jensen-Jarolim, Erika; Elnar, Arpiné A.; Ouamara, Nadia; Boyko, Nadiya; Coumoul, Xavier; Antignac, Jean-Philippe; Le Bizec, Bruno; Eppe, Gauthier; Renaut, Jenny; Bonn, Torsten; Guignard, Cédric; Ferrante, Margherita; Chiusano, Maria Liusa; Cuzzocrea, Salvatore; O’Keeffe, Gerard; Cryan, John; Bisson, Michelle; Barakat, Amina; Hmamouchi, Ihsane; Zawia, Nasser; Kanthasamy, Anumantha; Kisby, Glen E.; Alves, Rui; Pérez, Oscar Villacañas; Burgard, Kim; Spencer, Peter; Bomba, Norbert; Haranta, Martin; Zaitseva, Nina; May, Irina; Grojean, Stéphanie; Body-Malapel, Mathilde; Harari, Florencia; Harari, Raul; Yeghiazaryan, Kristina; Calabrese, Vittorio; Nemos, Christophe; Soulimani, Rachid; Evsevyeva, Maria E.; Mishenko, Elena A.; Kumukova, Zurida V.; Chudnovsky, Evgeniy V.; Smirnova, Tatyana A.; Ivanova, Ludmila V.; Eremin, Michail V.; Rostovtseva, Maria V.; Koshel, Vladimir I.; Sergeeva, Oksana V.; Konovalova, Nadesgda M.; Girotra, Shantanu; Debald, Manuel; Kuhn, Walther; Goncharenko, Vadym M.; Lushchyk, Ulyana; Grech, Godfrey; Konieczka, Katarzyna; Erwich, Jan Jaap; Costigliola, Vincenzo; Gembruch, Ulrich; Beniuk, Vasyl O.; Kalenska, Olga V.; Melnychuk, Olga; Gorbacheva, Irina A.; Orekhova, Lyudmila Y.; Tachalov, Vadim V.; Grechanyk, Olena I.; Abdullaiev, Rizvan Ya.; Hagan, Suzanne; Martin, Eilidh; Pearce, Ian; Oliver, Katherine; Haytac, Cenk; Salimov, Fariz; Yoksul, Servin; Kunin, Anatoly A.; Moiseeva, Natalia S.; Herrera-Imbroda, Bernardo; del Río-González, Sergio; Lara, Maria Fernanda; Angulo, Antonia; Machuca Santa-Cruz, Francisco Javier; Ionescu, John; Isamulaeva, Alfiya Z.; Magomedov, Shamil Sh.; Isamulaeva, Aida I.; Josifova, Tatjana; Kapalla, Marko; Kubáň, Juraj; Kent, Anthony; Fisher, Tom; Dias, Tilak; Topolčan, Ondřej; Kohl, Matthias; Kurchenko, Andrii I.; Beniuk, Vasyl A.; Strokan, Andriy M.; Kzhyshkowska, Julia; Gudima, Alexandru; Stankevich, Ksenia S.; Filimonov, Victor D.; Klüter, Harald; Mamontova, Evgeniya M.; Tverdokhlebov, Sergei I.; Lushchyk, Ulyana B.; Novytskyy, Viktor V.; Babii, Igor P.; Lushchyk, Nadiya G.; Riabets, Lyudmyla S.; Legka, Ivanna I.; Marcus-Kalish, Mira; Mitelpunkt, Alexis; Galili, Tal; Shachar, Neta; Benjamini, Yoav; Dereń, Ewelina; Kunin, Dmitry A.; Ippolitov, Yury A.; Morozov, Alexei N.; Chirkova, Natalia V.; Aliev, Nakhid T.; Abdelsayed, Rafik; Shi, Xing-Ming; Novák, Jaroslav; Štork, Milan; Zeman, Václav; Oosterhuis, Wytze P.; Theodorsson, Elvar; Kudryavtseva, Tatyana V.; Isaeva, Elena R.; Loboda, Ekaterina S.; Pazzagli, Mario; Malentacchi, Francesca; Mancini, Irene; Brandslund, Ivan; Vermeersch, Pieter; Schwab, Matthias; Marc, Janja; van Schaik, Ron H. N.; Siest, Gerard; Di Resta, Chiara; Pleva, Matus; Juhar, Jozef; Polívka jr., Jiří; Janků, Filip; Pešta, Martin; Doležal, Jan; Králíčková, Milena; Polívka, Jiří; Lukešová, Alena; Müllerová, Nina; Ševčík, Petr; Rohan, Vladimír; Richter, Kneginja; Miloseva, Lence; Niklewski, Günter; Acker, Jens; Niklewski, Guenter; Safonicheva, Olga; Sautin, Maxim; Sinelnikova, Janna; Secer, Songül; von Bandemer, Stephan; Shapira, Niva; Shcherbakov, Aleksandr; Shumilovich, Bogdan R.; Lipkind, Zhanna; Vorobieva, Yulia; Sudareva, Anastasiia V.; Smokovski, Ivica; Milenkovic, Tatjana; Solís-Herrera, Arturo; Arias-Esparza, María del Carmen; Sridhar, Krishna Chander; Studneva, Maria; Song, Sihong; Creeden, James; Мandrik, Мark; Tofail, Syed A. M.; Fiala, Ondřej; Karlíková, Marie; Svobodová, Šárka; Kučera, Radek; Fuchsová, Radka; Třeška, Vladislav; Šimánek, Václav; Pecen, Ladislav; Šoupal, Jan; Svačina, Štěpán; Tretyak, Evgeniya; Trovato, Francesca M.; Martines, Giuseppe Fabio; Brischetto, Daniela; Catalano, Daniela; Musumeci, Giuseppe; Trovato, Guglielmo M.; Tsangaris, George Th.; Anagnostopoulos, Athanasios K.; Verdú, José; Gutiérrez, German; Rovira, Jordi; Martinez, Marta; Green, Donna; Garson, Arthur; Tamburini, Elena; Cuomo, Stefano; Martinez-Leon, Juan; Abrisqueta, Teresa; Arredondo, Teresa; Vera, Cecilia; Fico, Giuseppe; Arribas, Fernando; Onderco, Martina; Vara, Isabel; Sambo, Francesco; Di Camillo, Barbara; Cobelli, Claudio; Facchinetti, Andrea; Bellazzi, Riccardo; Sacchi, Lucia; Dagliati, Arianna; Segnani, Daniele; Tibollo, Valentina; Ottaviano, Manuel; Gabriel, Rafael; Groop, Leif; Postma, Jacqueline; Martinez, Antonio; Hakaste, Liisa; Tuomi, Tiinamaija; Zarkogianni, Konstantia; Volchek, Igor; Pototskaya, Nina; Petrov, Andrey; Pototskaya, Nadezhda; Voog-Oras, Ülle; Jagur, Oksana; Leibur, Edvitar; Niibo, Priit; Jagomägi, Triin; Nguyen, Minh Son; Pruunsild, Chris; Piikov, Dagmar; Saag, Mare; Wang, Wei; Weinhäusel, Andreas; Pulverer, Walter; Wielscher, Matthias; Hofner, Manuela; Noehammer, Christa; Soldo, Regina; Hettegger, Peter; Gyurjan, Istvan; Kulovics, Ronald; Schönthaler, Silvia; Beikircher, Gabriel; Kriegner, Albert; Pabinger, Stephan; Vierlinger, Klemens; Yüzbaşıoğlu, Ayşe; Özgüç, Meral
    Table of contents A1 Predictive and prognostic biomarker panel for targeted application of radioembolisation improving individual outcomes in hepatocellular carcinoma Jella-Andrea Abraham, Olga Golubnitschaja A2 Integrated market access approach amplifying value of “Rx-CDx” Ildar Akhmetov A3 Disaster response: an opportunity to improve global healthcare Russell J. Andrews, Leonidas Quintana A4 USA PPPM: proscriptive, profligate, profiteering medicine-good for 1 % wealthy, not for 99 % unhealthy Russell J. Andrews A5 The role of IDO in a murine model of gingivitis: predictive and therapeutic potentials Babak Baban, Jun Yao Liu, Xu Qin, Tailing Wang, Mahmood S. Mozaffari A6 Specific diets for personalised treatment of diabetes type 2 Viktoriia V. Bati, Tamara V. Meleshko, Olga B. Levchuk, Nadiya V. Boyko A7 Towards personalized physiotherapeutic approach Joanna Bauer, Ewa Boerner, Halina Podbielska A8 Cells, animal, SHIME and in silico models for detection and verification of specific biomarkers of non-communicable chronic diseases Alojz Bomba, Viktor O. Petrov, Volodymyr G. Drobnych, Rostyslav V. Bubnov, Oksana M. Bykova, Nadiya V. Boyko A9 INTERACT-chronic care model: Self-treatment by patients with decision support e-Health solution Hans-Peter Brunner-La Rocca, Lutz Fleischhacker, Olga Golubnitschaja, Frank Heemskerk, Thomas Helms, Tiny Jaarsma, Judita Kinkorova, Jan Ramaekers, Peter Ruff, Ivana Schnur, Emilio Vanoli, Jose Verdu A10 PPPM in cardiovascular medicine in 2015 Hans-Peter Brunner-La Rocca A11 Magnetic resonance imaging of nanoparticles in mice, potential for theranostic and contrast media development – pilot results Rostyslav V. Bubnov, Sergiy A. Grabovetskyi, Olena M. Mykhalchenko, Natalia O. Tymoshok, Oleksandr B. Shcherbakov, Igor P. Semeniv, Mykola Y. Spivak A12 Ultrasound diagnosis for diabetic neuropathy - comparative study Rostyslav V. Bubnov, Tetyana V. Ostapenko A13 Ultrasound for stratification patients with diabetic foot ulcers for prevention and personalized treatment - pilot results Rostyslav V. Bubnov, Nazarii M. Kobyliak, Nadiya M. Zholobak, Mykola Ya. Spivak A14 Project ImaGenX – designing and executing a questionnaire on environment and lifestyle risk of breast cancer John Paul Cauchi A15 Genomics – a new structural brand of predictive, preventive and personalized medicine or the new driver as well? Dmitrii Cherepakhin, Marina Bakay, Artem Borovikov, Sergey Suchkov A16 Survey of questionnaires for evaluation of the quality of life in various medical fields Barbara Cieślik, Agnieszka Migasiewicz, Maria-Luiza Podbielska, Markus Pelleter, Agnieszka Giemza, Halina Podbielska A17 Personalized molecular treatment for muscular dystrophies Sebahattin Cirak A18 Secondary mutations in circulating tumour DNA for acquired drug resistance in patients with advanced ALK + NSCLC Marzia Del Re, Paola Bordi, Valentina Citi, Marta Palombi, Carmine Pinto, Marcello Tiseo, Romano Danesi A19 Recombinant species-specific FcεRI alpha proteins for diagnosis of IgE-mediated allergies in dogs, cats and horses Lukas Einhorn, Judit Fazekas, Martina Muhr, Alexandra Schoos, Lucia Panakova, Ina Herrmann, Krisztina Manzano-Szalai, Kumiko Oida, Edda Fiebiger, Josef Singer, Erika Jensen-Jarolim A20 Global methodology for developmental neurotoxicity testing in humans and animals early and chronically exposed to chemical contaminants Arpiné A. Elnar, Nadia Ouamara, Nadiya Boyko, Xavier Coumoul, Jean-Philippe Antignac, Bruno Le Bizec, Gauthier Eppe, Jenny Renaut, Torsten Bonn, Cédric Guignard, Margherita Ferrante, Maria Liusa Chiusano, Salvatore Cuzzocrea, Gerard O'Keeffe, John Cryan, Michelle Bisson, Amina Barakat, Ihsane Hmamouchi, Nasser Zawia, Anumantha Kanthasamy, Glen E. Kisby, Rui Alves, Oscar Villacañas Pérez, Kim Burgard, Peter Spencer, Norbert Bomba, Martin Haranta, Nina Zaitseva, Irina May, Stéphanie Grojean, Mathilde Body-Malapel, Florencia Harari, Raul Harari, Kristina Yeghiazaryan, Olga Golubnitschaja, Vittorio Calabrese, Christophe Nemos, Rachid Soulimani A21 Mental indicators at young people with attributes hypertension and pre-hypertension Maria E. Evsevyeva, Elena A. Mishenko, Zurida V. Kumukova, Evgeniy V. Chudnovsky, Tatyana A. Smirnova A22 On the approaches to the early diagnosis of stress-induced hypertension in young employees of State law enforcement agencies Maria E. Evsevyeva, Ludmila V. Ivanova, Michail V. Eremin, Maria V. Rostovtseva A23 Сentral aortic pressure and indexes of augmentation in young persons in view of risk factors Maria E. Evsevyeva, Michail V. Eremin, Vladimir I. Koshel, Oksana V. Sergeeva, Nadesgda M. Konovalova A24 Breast cancer prediction and prevention: Are reliable biomarkers in horizon? Shantanu Girotra, Olga Golubnitschaja A25 Flammer Syndrome and potential formation of pre-metastatic niches: A multi-centred study on phenotyping, patient stratification, prediction and potential prevention of aggressive breast cancer and metastatic disease Olga Golubnitschaja, Manuel Debald, Walther Kuhn, Kristina Yeghiazaryan, Rostyslav V. Bubnov, Vadym M. Goncharenko, Ulyana Lushchyk, Godfrey Grech, Katarzyna Konieczka A26 Innovative tools for prenatal diagnostics and monitoring: improving individual pregnancy outcomes and health-economy in EU Olga Golubnitschaja, Jan Jaap Erwich, Vincenzo Costigliola, Kristina Yeghiazaryan, Ulrich Gembruch A27 Immunohistochemical assessment of APUD cells in endometriosis Vadym M. Goncharenko, Vasyl O. Beniuk, Olga V. Kalenska, Rostyslav V. Bubnov A28 Updating personalized management algorithm of endometrial hyperplasia in pre-menopause women Vadym M. Goncharenko, Vasyl O. Beniuk, Rostyslav V. Bubnov, Olga Melnychuk A29 The personified treatment approach of polimorbid patients with periodontal inflammatory diseases Irina A. Gorbacheva, Lyudmila Y. Orekhova, Vadim V. Tachalov A30 Ukrainian experience in hybrid war – the challenge to update algorithms for personalized care and early prevention of different military injuries Olena I. Grechanyk, Rizvan Ya. Abdullaiev, Rostyslav V. Bubnov A31 Tear fluid biomarkers: a comparison of tear fluid sampling and storage protocols Suzanne Hagan, Eilidh Martin, Ian Pearce, Katherine Oliver A32 The correlation of dietary habits with gingival problems during menstruation Cenk Haytac, Fariz Salimov, Servin Yoksul, Anatoly A. Kunin, Natalia S. Moiseeva A33 Genomic medicine in a contemporary Spanish population of prostate cancer: our experience Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara, Antonia Angulo, Francisco Javier Machuca Santa-Cruz A34 Challenges, opportunities and collaborations for personalized medicine applicability in uro-oncological disease Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara A35 Metabolic hallmarks of cancer as targets for a personalized therapy John Ionescu A36 Influence of genetic polymorphism as a predictor of the development of periodontal disease in patients with gastric ulcer and 12 duodenal ulcer Alfiya Z. Isamulaeva, Anatoly A. Kunin, Shamil Sh. Magomedov, Aida I. Isamulaeva A37 Challenges in diabetic macular edema Tatjana Josifova A38 Overview of the EPMA strategies in laboratory medicine relevant for PPPM Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja, Vincenzo Costigliola A39 EPMA initiative for effective organization of medical travel: European concepts and criteria Vincenzo Costigliola, Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja A40 Design and innovation in e-textiles: implications for PPPM Anthony Kent, Tom Fisher, Tilak Dias A41 Biobank in Pilsen as a member of national node BBMRI_CZ Judita Kinkorová, Ondřej Topolčan A42 Big data in personalized medicine: hype and hope Matthias Kohl A43 The 3P approach as the platform of the European Dentistry Department (DPPPD) Anatoly A. Kunin, Natalia S. Moiseeva A44 The endometrium cytokine patterns for predictive diagnosis of proliferation severity and cancer prevention Andrii I. Kurchenko, Vasyl A. Beniuk, Vadym M. Goncharenko, Rostyslav V. Bubnov, Nadiya V. Boyko, Andriy M. Strokan A45 A monocyte-based in-vitro system for testing individual responses to the implanted material: future for personalized implant construction Julia Kzhyshkowska, Alexandru Gudima, Ksenia S. Stankevich, Victor D. Filimonov4, Harald Klüter, Evgeniya M. Mamontova, Sergei I. Tverdokhlebov A46 Prediction and prevention of adverse health effects by meteorological factors: Biomarker patterns and creation of a device for self-monitoring and integrated care Ulyana B. Lushchyk, Viktor V. Novytskyy, Igor P. Babii, Nadiya G. Lushchyk, Lyudmyla S. Riabets, Ivanna I. Legka A47 Targeting "disease signatures" towards personalized healthcare Mira Marcus-Kalish, Alexis Mitelpunkt, Tal Galili, Neta Shachar, Yoav Benjamini A48 Influence of the skin imperfection on the personal quality of life and possible tools for objective diagnosis Agnieszka Migasiewicz, Markus Pelleter, Joanna Bauer, Ewelina Dereń, Halina Podbielska A49 The new direction in caries prevention based on the ultrastructure of dental hard tissues and filling materials Natalia S. Moiseeva, Anatoly A. Kunin, Dmitry A. Kunin A50 The use of LED radiation in prevention of dental diseases Natalia S. Moiseeva, Yury A. Ippolitov, Dmitry A. Kunin, Alexei N. Morozov, Natalia V. Chirkova, Nakhid T. Aliev A51 Status of endothelial progenitor cells in diabetic nephropathy: predictive and preventive potentials Mahmood S. Mozaffari, Jun Yao Liu, Babak Baban A52 The status of glucocorticoid-induced leucine zipper protein in salivary gland in Sjögren’s syndrome: predictive and personalized treatment potentials Mahmood S. Mozaffari, Jun Yao Liu, Rafik Abdelsayed, Xing-Ming Shi, Babak Baban A53 Maximal aerobic capacity - important quality marker of health Jaroslav Novák, Milan Štork, Václav Zeman A54 The EMPOWER project: laboratory medicine and Horizon 2020 Wytze P. Oosterhuis, Elvar Theodorsson A55 Personality profile manifestations in patient’s attitude to oral care and adherence to doctor’s prescriptions Lyudmila Y. Orekhova, Tatyana V. Kudryavtseva, Elena R. Isaeva, Vadim V. Tachalov, Ekaterina S. Loboda A56 Results of an European survey on personalized medicine addressed to directions of laboratory medicine Mario Pazzagli, Francesca Malentacchi, Irene Mancini, Ivan Brandslund, Pieter Vermeersch, Matthias Schwab, Janja Marc, Ron H.N. van Schaik, Gerard Siest, Elvar Theodorsson, Chiara Di Resta A57 MCI or early dementia predictive speech based diagnosis techniques Matus Pleva, Jozef Juhar A58 Personalized speech based mobile application for eHealth Matus Pleva, Jozef Juhar A59 Circulating tumor cell-free DNA as the biomarker in the management of cancer patients Jiří Polívka jr., Filip Janků, Martin Pešta, Jan Doležal, Milena Králíčková, Jiří Polívka A60 Complex stroke care – educational programme in Stroke Centre University Hospital Plzen Jiří Polívka, Alena Lukešová, Nina Müllerová, Petr Ševčík, Vladimír Rohan A61 Sleep apnea and sleep fragmentation contribute to brain aging Kneginja Richter, Lence Miloseva, Günter Niklewski A62 Personalised approach for sleep disturbances in shift workers Kneginja Richter, Jens Acker, Guenter Niklewski A63 Medical travel and innovative PPPM clusters: new concept of integration Olga Safonicheva, Vincenzo Costigliola A64 Medical travel and women health Olga Safonicheva A65 Continuity of generations in the training of specialists in the field of reconstructive microsurgery Maxim Sautin, Janna Sinelnikova, Sergey Suchkov A66 Telemonitoring of stroke patients – empirical evidence of individual risk management results from an observational study in Germany Songül Secer, Stephan von Bandemer A67 Women’s increasing breast cancer risk with n-6 fatty acid intake explained by estrogen-fatty acid interactive effect on DNA damage: implications for gender-specific nutrition within personalized medicine Niva Shapira A68 Cytobacterioscopy of the gingival crevicular fluid as a method for preventive diagnosis of periodontal diseases Aleksandr Shcherbakov, Anatoly A. Kunin, Natalia S. Moiseeva A69 Use of specially treated composites in dentistry to avoid violations of aesthetics Bogdan R. Shumilovich, Zhanna Lipkind, Yulia Vorobieva, Dmitry A. Kunin, Anastasiia V. Sudareva A70 National eHealth system – platform for preventive, predictive and personalized diabetes care Ivica Smokovski, Tatjana Milenkovic A72 The common energy levels of Prof. Szent-Györgyi, the intrinsic chemistry of melanin, and the muscle physiopathology. 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Anagnostopoulos A82 Integrated Ecosystem for an Integrated Care model for Heart Failure (HF) patients including related comorbidities (ZENITH) José Verdú, German Gutiérrez, Jordi Rovira, Marta Martinez, Lutz Fleischhacker, Donna Green, Arthur Garson, Elena Tamburini, Stefano Cuomo, Juan Martinez-Leon, Teresa Abrisqueta, Hans-Peter Brunner-La Rocca, Tiny Jaarsma, Teresa Arredondo, Cecilia Vera, Giuseppe Fico, Olga Golubnitschaja, Fernando Arribas, Martina Onderco, Isabel Vara, on behalf of ZENITH consortium A83 Predictive, preventive and personalized medicine in diabetes onset and complication (MOSAIC project) José Verdú, Francesco Sambo, Barbara Di Camillo, Claudio Cobelli, Andrea Facchinetti, Giuseppe Fico, Riccardo Bellazzi, Lucia Sacchi, Arianna Dagliati, Daniele Segnani, Valentina Tibollo, Manuel Ottaviano, Rafael Gabriel, Leif Groop, Jacqueline Postma, Antonio Martinez, Liisa Hakaste, Tiinamaija Tuomi, Konstantia Zarkogianni, on behalf of MOSAIC consortium A84 Possibilities for personalized therapy of diabetes using in vitro screening of insulin and oral hypoglycemic agents Igor Volchek, Nina Pototskaya, Andrey Petrov A85 The innovative technology for personalized therapy of human diseases based on in vitro drug screening Igor Volchek, Nadezhda Pototskaya, Andrey Petrov A86 Bone destruction and temporomandibular joint: predictive markers, pathogenetic aspects and quality of life Ülle Voog-Oras, Oksana Jagur, Edvitar Leibur, Priit Niibo, Triin Jagomägi, Minh Son Nguyen, Chris Pruunsild, Dagmar Piikov, Mare Saag A87 Sub-optimal health management – global vision for concepts in medical travel Wei Wang A88 Sub-optimal health management: synergic PPPM-TCAM approach Wei Wang A89 Innovative technologies for minimal invasive diagnostics Andreas Weinhäusel, Walter Pulverer, Matthias Wielscher, Manuela Hofner, Christa Noehammer, Regina Soldo, Peter Hettegger, Istvan Gyurjan, Ronald Kulovics, Silvia Schönthaler, Gabriel Beikircher, Albert Kriegner, Stephan Pabinger, Klemens Vierlinger A90 Rare disease diobanks for personalized medicine Ayşe Yüzbaşıoğlu, Meral Özgüç, Member of EuroBioBank - European Network of DNA, Cell and Tissue Banks for Rare Diseases
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    Fc-Epsilon-RI, the High Affinity IgE-Receptor, Is Robustly Expressed in the Upper Gastrointestinal Tract and Modulated by Mucosal Inflammation
    (Public Library of Science, 2012) Bannert, Christina; Bidmon-Fliegenschnee, Bettina; Stary, Georg; Hotzy, Florian; Stift, Judith; Nurko, Samuel; Szépfalusi, Zsolt; Fiebiger, Edda; Dehlink, Eleonora
    Background: The role of the high affinity IgE receptor, FcεRI, in IgE-mediated immune responses of the gastrointestinal (GI) mucosa is poorly understood. Currently, a detailed characterization of FcεRI expression throughout the human gut is lacking. The aim of this study was to define the expression pattern of FcεRI in the GI tract. Methods/Principal Findings: We compared FcεRI expression in children with gastritis/esophagitis (n = 10), celiac disease (n = 10), inflammatory bowel disease (IBD) (n = 9), and normal mucosa (n = 5). The α–subunit of FcεRI (FcεRIα), detected by immunohistochemistry, was found on cells infiltrating the mucosa of the esophagus, the stomach, and the duodenum, but was rarely detected in more distal sections of the GI tract. Accordingly, quantitative RT-PCR analysis on esophagus, stomach, duodenum, colon, and rectum biopsies revealed that FcεRIα and -β expression levels decreased towards the distal intestine. mRNA transcripts of the common Fc-receptor-γ chain were present in the entire GI mucosa. Double-immunofluorescence staining of esophageal specimens confirmed that FcεRIα was expressed on intraepithelial mast cells and Langerhans cells. The mRNA expression levels of the α, β, and γ subunits of FcεRI did not correlate with total serum IgE but were associated with mucosal inflammation. Conclusion/Significance: Our data define the upper GI tract as the main site for IgE-mediated immune activation via FcεRI. Tissue mRNA levels of FcεRIα are regulated by inflammatory conditions rather than serum IgE, indicating that FcεRI might also play a role in pathologies other than allergy.
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    Screen for ISG15-crossreactive Deubiquitinases
    (Public Library of Science, 2007) Catic, Andre; Fiebiger, Edda; Korbel, Gregory; Blom, Daniël; Galardy, Paul J.; Ploegh, Hidde L.
    Background: The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15. Results: We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43). USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. Conclusions: By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice.
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    Relationships Between Levels of Serum IgE, Cell-Bound IgE, and IgE-Receptors on Peripheral Blood Cells in a Pediatric Population
    (Public Library of Science, 2010) Ratner, Adam J.; Dehlink, Eleonora; Yen, Elizabeth Hechavarria; Nurko, Samuel; Fiebiger, Edda
    Background: Elevated serum immunoglobulin (Ig) E is a diagnostic marker of immediate-type allergic reactions. We hypothesize that serum IgE does not necessarily reflect total body IgE because in vivo IgE can be bound to cell surface receptors such as FcεRI and FcεRII (CD23). The aim of this study was to analyze the relationships between levels of serum IgE, cell-bound IgE, and IgE-receptors on peripheral blood cells in a pediatric population. Methodology: Whole blood samples from 48 children (26 boys, 22 girls, mean age 10,3±5,4 years) were analyzed by flow cytometry for FcεRI, CD23, and cell-bound IgE on dendritic cells (CD11c+MHC class II+), monocytes (CD14+), basophils (CD123+MHC class II-) and neutrophils (myeloperoxidase+). Total serum IgE was measured by ELISA and converted into z-units to account for age-dependent normal ranges. Correlations were calculated using Spearman rank correlation test. Principal Findings: Dendritic cells, monocytes, basophils, and neutrophils expressed the high affinity IgE-receptor FcεRI. Dendritic cells and monocytes also expressed the low affinity receptor CD23. The majority of IgE-receptor positive cells carried IgE on their surface. Expression of both IgE receptors was tightly correlated with cell-bound IgE. In general, cell-bound IgE on FcεRI+ cells correlated well with serum IgE. However, some patients carried high amounts of cell-bound IgE despite low total serum IgE levels. Conclusion/Significance: In pediatric patients, levels of age-adjusted serum IgE, cell-bound IgE, and FcεRI correlate. Even in the absence of elevated levels of serum IgE, cell-bound IgE can be detected on peripheral blood cells in a subgroup of patients.
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    A Soluble Form of the High Affinity IgE Receptor, Fc-Epsilon-RI, Circulates in Human Serum
    (Public Library of Science, 2011) Dehlink, Eleonora; Platzer, Barbara; Baker, Alexandra H.; LaRosa, Jessica; Pardo, Michael; Dwyer, Peter; Yen, Elizabeth Hechavarria; Szepfalusi, Zsolt; Nurko, Samuel; Fiebiger, Edda
    Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFc\(\epsilon\)RI), the high affinity receptor for IgE. sFc (sFc\(\epsilon\)RI immunoprecipitates as a protein of ~40 kDa and contains an intact IgE-binding site. In human serum, sFc (sFc\(\epsilon\)RI) is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFc\(\epsilon\)RI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFc\( \epsilon \)RI. After IgE-antigen-mediated crosslinking of surface Fc\(\epsilon\)RI, we detect sFc\(\epsilon\)RI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFc\(\epsilon\)RI can block binding of IgE to Fc\(\epsilon\)RI expressed at the cell surface. In summary, we here describe the alpha-chain of Fc\(\epsilon\)RI as a circulating soluble IgE receptor isoform in human serum.