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1. Systemic and local evidence for complement involvement in chronic spontaneous urticaria

Author

Mehran Alizadeh Aghdam, Mignon van den Elzen, Harmieke van Os‐Medendorp, Marijke R. van Dijk, Edward F. Knol, André C. Knulst, Heike Röckmann, and Henny G. Otten

Subjects
blood, complement, omalizumab, skin, urticaria, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background The pathogenesis of chronic spontaneous urticaria (CSU), including the mechanism of action of omalizumab, remain unclear. We hypothesized complement system involvement given the often fast clinical response induced by treatment, including omalizumab. Therefore, we assessed the role of various complement factors surrounding omalizumab treatment. Methods Thirty CSU patients (median age 42 [range 21–70]; 73 % female) with a median once daily Urticaria Activity Score over 7 days (UAS7) score at baseline of 31.5 points were enrolled. Treatment consisted of six administrations of 300 mg omalizumab every 4 weeks succeeded by a follow‐up period of 12 weeks. Four punch skin biopsies were taken per patient; at baseline from lesional skin, at baseline from nonlesional skin, and after 1 and 7 days from formerly lesional skin. Complement activity, including C1q, C3, C3bc/C3, C4, C4bc/C4, C5a, and Membrane Attack Complex in peripheral blood were analyzed and complement activation in the skin was determined by the analysis of C4d deposition. Results were related to the clinical response to omalizumab. Results Fifteen patients showed a UAS7 score of 6 or lower (median 0) at Week 24, 15 patients did not (median 16). Lesional skin biopsies at baseline revealed complement deposition (C4d) in blood vessels in the papillary dermis of 53% (16/30) of the patients, which suggests involvement of immune complexes in the pathogenesis of urticaria. Moreover, indication of increased complement activation in CSU was substantiated by increased C5a levels in peripheral blood compared to healthy controls (p = 0.010). The clinical effect of omalizumab could not be linked to the variation of complement components. Conclusions Both C4d deposition in lesional skin and elevated C5a levels in peripheral blood indicate the involvement of complement activation in the pathogenesis of CSU. No correlation was found between omalizumab and activation of complement indicative of independent processes in the immunopathogenesis of CSU.

Published
2021
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2. Aged mice display altered numbers and phenotype of basophils, and bone marrow-derived basophil activation, with a limited role for aging-associated microbiota

Author

Adriaan A. van Beek, Floris Fransen, Ben Meijer, Paul de Vos, Edward F. Knol, and Huub F. J. Savelkoul

Subjects
Aging, Basophils, Immunity, Microbiota, Bone marrow, Spleen, Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract Background The influence of age on basophils is poorly understood, as well as the effect of aging-associated microbiota on basophils. Therefore, we studied the influence of aging and aging-associated microbiota on basophil frequency and phenotype, and differentiation from basophil precursors. Results Basophils became more abundant in bone marrow (BM) and spleens of 19-month-old mice compared with 4-month-old mice. Aged basophils tended to express less CD200R3 and more CD123, both in BM and spleen. Differences in microbiota composition with aging were confirmed by 16S sequencing. Microbiota transfers from young and old mice to germ-free recipients revealed that CD11b tended to be lowered on splenic basophils by aging-associated microbiota. Furthermore, abundance of Alistipes, Oscillibacter, Bacteroidetes RC9 gut group, and S24–7 family positively correlated and CD123 expression, whereas Akkermansia abundance negatively correlated with basophils numbers. Subsequently, we purified FcεRIα+CD11c−CD117− BM-derived basophils and found that those from aged mice expressed lower levels of CD11b upon stimulation. Higher frequencies of IL-4+ basophils were generated from basophil precursors of aged mice, which could be reproduced in basophils derived from germ-free recipients of aging-associated microbiota. Conclusions Collectively, these results show the influence of aging on basophils. Furthermore, this study shows that aging-associated microbiota altered activation of BM-derived basophils in a similar fashion as observed in BM-derived basophils from aged mice.

Published
2018
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3. Sensitization to PR-10 proteins is indicative of distinctive sensitization patterns in adults with a suspected food allergy

Author

Mark A. Blankestijn, André C. Knulst, Edward F. Knol, Thuy-My Le, Heike Rockmann, Henny G. Otten, and Rob J. B. Klemans

Subjects
ImmunoCAP ISAC, Food allergy, PR-10, Specific IgE, Storage proteins, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background The extent of co-sensitization within and between food protein families in an adult population is largely unknown. This study aimed to identify the most frequently recognized components in the PR-10 and storage protein family, as well as patterns in (co-)sensitization, in a birch-endemic area. Methods Results of ImmunoCAP ISAC, performed during routine care in Dutch adult outpatients suspected of food allergy, were collected. Results A total of 305 patients were selected, aged 16–79 years (median 32 years). Sensitization to one or more PR-10 proteins was most frequent (74% of all subjects), followed by 35% to storage protein and 15% to nsLTPs. Within the PR-10 family, subjects were most often sensitized to Bet v 1 (73% of 305), Cor a 1.04 (72%) and Mal d 1 (68%). Sensitization to PR-10s from soy, celery and kiwi occurred distinctively less often ( 70%). Subjects sensitized to these ‘less common PR-10 proteins’ were sensitized to more food and inhalant components on the ISAC, compared to subjects sensitized to ‘common PR-10 proteins’ (median 22 vs 13 out of 112, p

Published
2017
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4. Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

Author

Jolanda H. M. van Bilsen, Edyta Sienkiewicz-Szłapka, Daniel Lozano-Ojalvo, Linette E. M. Willemsen, Celia M. Antunes, Elena Molina, Joost J. Smit, Barbara Wróblewska, Harry J. Wichers, Edward F. Knol, Gregory S. Ladics, Raymond H. H. Pieters, Sandra Denery-Papini, Yvonne M. Vissers, Simona L. Bavaro, Colette Larré, Kitty C. M. Verhoeckx, and Erwin L. Roggen

Subjects
Adverse outcome pathway, Key events, Key event relations, Food allergy, Sensitization, Mechanistic understanding, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). Main body The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell–cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. Conclusion The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs.

Published
2017
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5. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Guillaume Pouessel, Claire Claverie, Julien Labreuche, Jean-Marie Renaudin, Aimée Dorkenoo, Mireille Eb, Anne Moneret-Vautrin, Antoine Deschildre, Stephane Leteurtre, Linus Grabenhenrich, Margitta Worm, Sabine Dölle, Kathrin Scherer, Isidor Hutteger, Morten Christensen, Carsten Bindslev-Jensen, Charlotte Mortz, Esben Eller, Henrik Fomsgaard Kjaer, Leonor Carneiro-Leão, Jenny Badas, Alice Coimbra, Dikla Pivko Levy, Moshe Ben-Shoshan, Ayelet Rimon, Shira Benor, Nicolette J. T. Arends, Nikki Edelbroek, Hans de Groot, Joyce A. M. Emons, H. Kim A. Brand, Dirk Verhoeven, Leonieke N. van Veen, Nicolette W. de Jong, Geunwoong Noh, Eun Ha Jang, Mariona Pascal, Olga Dominguez, Mònica Piquer, Montserrat Alvaro, Rosa Jimenez-Feijoo, Jaime Lozano, Adriana Machinena, Maria del Mar Folqué, Maria Teresa Giner, Ana María Plaza, Paul Turner, Nandinee Patel, Marta Vazquez-Ortiz, Sarah Lindsley, Lucy Walker, Simon Rosenberg, Adriano Mari, Claudia Alessandri, Ivana Giangrieco, Lisa Tuppo, Chiara Rafaiani, Georg Mitterer, Michela Ciancamerla, Rosetta Ferrara, Maria Livia Bernardi, Danila Zennaro, Maurizio Tamburrini, Maria Antonetta Ciardiello, Christian Harwanegg, Antonio Fernandez, Regina Selb, Philippe Egenmann, Michelle Epstein, Karin Hoffmann-Sommergruber, Frits Koning, Martinus Lovik, E. N. Clare Mills, Javier Moreno, Henk van Loveren, Jean-Michel Wal, Susanne Diesner, Cornelia Bergmayr, Barbara Pfitzner, Vera Elisabeth Assmann, Philipp Starkl, David Endesfelder, Thomas Eiwegger, Zsolt Szepfalusi, Heinz Fehrenbach, Erika Jensen-Jarolim, Anton Hartmann, Isabella Pali-Schöll, Eva Untersmayr, Soren Wille, Peter Meyer, Caroline Klingebiel, Jonas Lidholm, Angelica Ehrenberg, Jonas Östling, Isabelle Cleach, Jean-Louis Mège, Joana Vitte, Roberta Aina, Pawel Dubiela, Sabine Pfeifer, Merima Bublin, Christian Radauer, Piotr Humeniuk, Stefan Kabasser, Riccardo Asero, Gador Bogas, Francisca Gomez, Paloma Campo, Maria Salas, Inmaculada Doña, Esther Barrionuevo, Maria Auxiliadora Guerrero, Cristobalina Mayorga, Ana Prieto, Domingo Barber, Maria Jose Torres, Annette Jamin, Andrea Wangorsch, Barbara Ballmer, Stefan Vieths, Stephan Scheurer, Danijela Apostolovic, Jelena Mihailovic, Maja Krstic, Maria Starkhammar, Tanja Cirkovic Velickovic, Carl Hamsten, Marianne van Hage, Francine C. van Erp, Edward F. Knol, Hannah M. Kansen, Bo Pontoppidan, Yolanda Meijer, Cornelis K. van der Ent, André C. Knulst, Rebekah Sayers, Helen Brown, Adnan Custovic, Angela Simpson, Claire Mills, Juliane Schulz, Network for Online Registration of Anaphylaxis (NORA), Jaap Akkerdaas, Muriel Totis, Annabelle Capt, Corinne Herouet-Guicheney, Ronald van Ree, Tushar Banerjee, Antima Banerjee, Mathilde Claude, Grégory Bouchaud, Roberta Lupi, Laure Castan, Olivier Tranquet, Sandra Denery-Papini, Marie Bodinier, Chantal Brossard, Rosella De Poi, Elisa Gritti, Emiliano De Dominicis, Bert Popping, Patrizia Polverino de Laureto, Kati Palosuo, Anna Kaarina Kukkonen, Anna Pelkonen, Mika Mäkelä, Nanju Alice Lee, Johanna Rost, Sridevi Muralidharan, Dianne Campbell, Sam Mehr, Catherine Nock, Joseph Baumert, Steve Taylor, Carla Mastrorilli, Salvatore Tripodi, Carlo Caffarelli, Serena Perna, Andrea Di Rienzo Businco, Ifigenia Sfika, Arianna Dondi, Annamaria Bianchi, Carlotta Povesi Dascola, Giampaolo Ricci, Francesca Cipriani, Nunzia Maiello, Michele Miraglia del Giudice, Tullio Frediani, Simone Frediani, Francesco Macrì, Chiara Pistoletti, Iride Dello Iacono, Maria Francesca Patria, Elena Varin, Diego Peroni, Pasquale Comberiati, Loredana Chini, Viviana Moschese, Sandra Lucarelli, Roberto Bernardini, Giuseppe Pingitore, Umberto Pelosi, Roberta Olcese, Matteo Moretti, Anastasia Cirisano, Diego Faggian, Alessandro Travaglini, Mario Plebani, Maria Carmen Verga, Mauro Calvani, Paolo Giordani, Paolo Maria Matricardi, Noe Ontiveros, Francisco Cabrera-Chavez, Julie Galand, Etienne Beaudouin, The Anaphylaxis Working Group of the French Allergology SocietyThe Anaphylaxis Working Group of the French Allergology Society, Florence Pineau, Shinobu Sakai, Kayoko Matsunaga, Reiko Teshima, Colette Larré, Sandra Denery, Sebastian Tschirner, Valérie Trendelenburg, Gabriele Schulz, Bodo Niggemann, Kirsten Beyer, Youcef Bouferkas, Younes Belabbas, Djamel Saidi, Omar Kheroua, Kamel Eddine El Mecherfi, Malika Guendouz, Abir Haddi, Hanane Kaddouri, Luis Amaral, Ana Pereira, Susana Rodrigues, Mareen Datema, Laurian Jongejan, Michael Clausen, Andre Knulst, Nikolaos Papadopoulos, Marek Kowalski, Frédéric de Blay, Aeilko Zwinderman, Karin Hoffman-Sommergruber, Barbara Ballmer-Weber, Montserrat Fernandez-Rivas, Shan Deng, Jia Yin, Charlotte Eisenmann, Maria Nassiri, Rabea Reinert, Johanna P. M. van der Valk, Roy Gerth van Wijk, Yvonne Vergouwe, Ewout W. Steyerberg, Marit Reitsma, Harry J. Wichers, Huub F. J. Savelkoul, Berber Vlieg-Boerstra, Anthony E. J. Dubois, Fabrícia Carolino, Ana Rodolfo, Josefina Cernadas, Dasha Roa-Medellín, Ana Rodriguez-Fernandez, Joaquín Navarro, Vicente Albendiz, María Luisa Baeza, Sonsoles Intente-Herrero, Andrea Mikkelsen, Kirsten Mehlig, Lauren Lissner, Linda Verrill, Stefano Luccioli, Jolanda van Bilsen, Frieke Kuper, André Wolterbeek, Tanja Rouhani Rankouhi, Lars Verschuren, Hilde Cnossen, Prescilla Jeurink, Johan Garssen, Léon Knippels, Jossie Garthoff, Geert Houben, Winfried Leeman, M. Eleonore Pettersson, Afke M. M. Schins, Gerard H. Koppelman, Boudewjin J. Kollen, Svitlana Zubchenko, Sarah Kuntz, Pablo Mérida, Montserrat Álvaro, Monica Piquer, Carmen Riggioni, Juan Heber Castellanos, Rosa Jimenez, Melanie Cap, Elodie Drumez, Stéphanie Lejeune, Caroline Thumerelle, Clémence Mordacq, Véronique Nève, Sonia Ricò, Margherita Varini, Rita Nocerino, Linda Cosenza, Antonio Amoroso, Margherita Di Costanzo, Carmen Di Scala, Giorgio Bedogni, Roberto Berni Canani, Paul J. Turner, Paloma Poza-Guedes, Ruperto González-Pérez, Inmaculada Sánchez-Machín, Victor Matheu-Delgado, Erik Wambre, Anne-Sofie Ballegaard, Charlotte Madsen, Juliane Gregersen, Katrine Lindholm Bøgh, Philippe Aubert, Michel Neunlist, Antoine Magnan, Daniel Lozano-Ojalvo, Alba Pablos-Tanarro, Leticia Pérez-Rodríguez, Elena Molina, Rosina López-Fandiño, Akila Rekima, Patricia Macchiaverni, Mathilde Turfkruyer, Sebastien Holvoet, Lénaïck Dupuis, Nour Baiz, Isabella Annesi-Maesano, Annick Mercenier, Sophie Nutten, Valérie Verhasselt, Ines Mrakovcic-Sutic, Srdan Banac, Ivana Sutic, Zdenka Baricev-Novakovic, Ingrid Sutic, Valentino Pavisic, Rosa Muñoz-Cano, Teodoríkez Jiménez-Rodríguez, Daniel Corbacho, Jordi Roca-Ferrer, Joan Bartra, Aleksandar Bulog, Vladimir Micovic, Lidia Markiewicz, Agata Szymkiewicz, Anna Szyc, Barbara Wróblewska, Bryan M. Harvey, Lucien F. Harthoorn, A. Wesley Burks, Georgios Rentzos, Anna-Lena Bramstång Björk, Ulf Bengtsson, Colin Barber, Chrystyna Kalicinsky, Christine Breynaert, Lieve Coorevits, Cornelia Jansen, Erna Van Hoeyveld, Kristin Verbeke, Anne-Marie Kochuyt, Rik Schrijvers, Diana Deleanu, Adriana Muntean, Maria Konstantakopoulou, Maria Pasioti, Anastasia Papadopoulou, Anna Iliopoulou, Nikolaos Mikos, Evangelia Kompoti, Eunice Dias de Castro, Borja Bartalomé, Kok Loong Ue, Elizabeth Griffiths, Stephen Till, Kate Grimshaw, Graham Roberts, Anna Selby, Indre Butiene, Jose Ignacio Larco, Ruta Dubakiene, Ana Fiandor, Alessandro Fiocchi, Nikos Papadopoulos, Sigurveig Sigurdardottir, Aline Sprikkelman, Anne-Fleur Schoemaker, Paraskevi Xepapadaki, Thomas Keil, Zizi Cojocariu, Beatriz Secades Barbado, Vasti Iancu, Esozia Arroabarren, Marta Goñi Esarte, Miren Arteaga, Mayra Coutinho Andrade, Denise Borges, Jorge Kalil, Pedro Giavina Bianchi, Rosana Camara Agondi, Rinkesh Kumar Gupta, Akanksha Sharma, Kriti Gupta, Mukul Das, Premendra Dwivedi, Rusudan Karseladze, Liana Jorjoliani, Lali Saginadze, Mariam Tskhakaia, Katia Basello, Gabriele Piuri, Attilio Francesco Speciani, Michela Carola Speciani, Carla Camerotto, Francesco Zinno, Olga Pakholchuk, Svitlana Nedelska, Stefano Pattini, Maria Teresa Costantino, Silvia Peveri, Danilo Villalta, Eleonora Savi, Andrea Costanzi, Vera A. Revyakina, Marina A. Kiseleva, Elena D. Kuvshinova, Inna A. Larkova, Anton A. Shekhetov, Diana Silva, André Moreira, José Plácido, Hanneke van der Kleij, Esther van Twuijver, Robbert Sutorius, Pieter-Jan de Kam, Jenny van Odijk, Helen Lindqvist, Elin Lustig, Amyra Ali Azamar Jácome, Karla Leversia Borjas Aguilar, Miguel García Domínguez, David Alejandro Mendoza Hernández, Cristiano Caruso, Cono Casale, Gian Lodovico Rapaccini, Antonino Romano, Italo De Vitis, Renata R. Cocco, Carolina Aranda, Marcia C. Mallozi, Jackeline F. Motta, Lilian Moraes, Antonio Pastorino, Nelson Rosario, Ekaterini Goudouris, Arnaldo Porto, Neusa F. Wandalsen, Emanuel Sarinho, Flavio Sano, Dirceu Solé, Constantinos Pitsios, Maria Petrodimopoulou, Ekaterini Papadopoulou, Maria Passioti, Meropi Kontogianni, Nino Adamia, Ekaterina Khaleva, Ana Prieto del Prado, George Du Toit, Edyta Krzych, Urszula Samolinska-Zawisza, Konrad Furmanczyk, Aneta Tomaszewska, Filip Raciborski, Agnieszka Lipiec, Piotr Samel-Kowalik, Artur Walkiewicz, Jacek Borowicz, Boleslaw Samolinski, Aimee Lou Nano, Marysia Recto, Maria Luisa Somoza, Natalia Blanca López, Diana Pérez Alzate, Francisco Javier Ruano, Maria Isabel Garcimartín, Elisa Haroun, Maria Vázquez de la Torre, Antonia Rojas, Montserrat López Onieva, Gabriela Canto, Alexandra Rodrigues, Andreia Forno, António Jorge Cabral, Rute Gonçalves, Ilya Vorozhko, Tatyana Sentsova, Olga Chernyak, Svetlana Denisova, Lidia Ilènko, Valery Muhortnich, Caroline Zimmermann, Alexander Rohrbach, Faisal R. Bakhsh, Kollen Boudewijn, Anne-Marie Oomkes-Pilon, Dorien Van Ginkle, Mira Šilar, Anja Jeverica, Tina Vesel, Tadej Avčin, Peter Korošec, Johanna van der Valk, Irene Berends, Nicolette Arends, Maurits van Maaren, Harry Wichers, Joyce Emons, Anthony Dubois, Nicolette de Jong, Oksana Matsyura, Lesya Besh, Chung-Hsiung Huang, Tong-Rong Jan, Gary Stiefel, Jean Tratt, Kerrie Kirk, Fabricia Carolino, Stefania Arasi, Lucia Caminiti, Giuseppe Crisafulli, Chiara Fiamingo, Jlenia Fresta, Giovanni Pajno, Ben Remington, Astrid Kruizinga, W. Marty Blom, Joost Westerhout, Sabina Bijlsma, Joe Baumert, Mark Blankestijn, Henny Otten, Rob Klemans, Anouska D. Michelsen-Huisman, Harmieke van Os-Medendorp, Astrid G. Kruizinga, Astrid Versluis, Gert van Duijn, H. Mary-Lene de Zeeuw-Brouwer, Jacqueline J. M. Castenmiller, Hub P. J. M. Noteborn, Geert F. Houben, Kristian Bravin, David Luyt, Bushra Javed, Phil Couch, Christopher Munro, Phil Padfield, Matt Sperrin, Aideen Byrne, Lizalet Oosthuizen, Carina Kelleher, Fiona Ward, Niamh Brosnan, Graham King, Eva Corbet, Josué Alejandro Huertas Guzmán, Montserrat Bosque García, Oscar Asensio, Laura Valdesoiro Navarrete, Helena Larramona, Xavier Domingo Miró, Katarzyna Pyrz, Moira Austin, Yanne Boloh, Philip Couch, Deirdre Galloway, Pilar Hernandez, Jonathan O’B. Hourihane, Fiona Kenna, Barbara Majkowska-Wojciechowska, Lynne Regent, Marina Themisb, Sabine Schnadt, Aida Semic-Jusufagic, Audrey Dunn Galvin, Tiina Kauppila, Mikael Kuitunen, Nikolaos A. Kitsioulis, Nikolaos Douladiris, Sofia Kostoudi, Ioanna Manolaraki, Dimitris Mitsias, Emmanouil Manousakis, Nikolaos G. Papadopoulos, Rebecca Knibb, Jennifer Hammond, Richard Cooke, Jaakko Yrjänä, Anna-Maija Hanni, Päivi Vähäsarja, Oona Mustonen, Teija Dunder, Petri Kulmala, Eva Lasa, Carmen D’Amelio, Sara Martínez, Alejandro Joral, Gabriel Gastaminza, Maria Jose Goikoetxea, David C. A. Candy, Marleen T. J. Van Ampting, Manon M. Oude Nijhuis, Assad M. Butt, Diego G. Peroni, Adam T. Fox, Jan Knol, Louise J. Michaelis, Ines Padua, Patricia Padrao, Pedro Moreira, Renata Barros, Hanan Sharif, Manzoor Ahmed, Nehad Gomaa, Joris Mens, Koen Smit, Frans Timmermans, Tomaž Poredoš, Anja Koren Jeverica, Marjeta Sedmak, Evgen Benedik, Meta Accetto, Mirjana Zupančič, Glauce Yonamine, Gustavo Soldateli, Bruna Aquilante, Antonio Carlos Pastorino, Cleonir Lui de Moraes Beck, Andrea Keiko Gushken, Mayra de Barros Dorna, Cristiane Nunes dos Santos, Ana Paula Moschione Castro, Abdulhadi Al-Qahtani, Rand Arnaout, Agha Rehan Khaliq, Rashid Amin, Farrukh Sheikh, Jorge Alvarez, Marta Anda, Miriam Palacios, Montserrat De Prada, Carmen Ponce, Bianca Balbino, Riccardo Sibilano, Thomas Marichal, Nicolas Gaudenzio, Hajime Karasuyama, Pierre Bruhns, Mindy Tsai, Laurent L. Reber, Stephen J. Galli, Ana Reis Ferreira, Josefina R. Cernadas, Aida del Campo García, Sara Pereiro Fernández, Nerea Sarmiento Carrera, Fernando Bandrés Sánchez-Cruz, José Ramón Fernández Lorenzo, Stephanie Claus, Claudia Pföhler, Franziska Ruëff, Regina Treudler, Mercedes Escarrer Jaume, Agustin Madroñero, Maria Teresa Guerra Perez, Juan Carlos Julia, Charlotte Hands Plovdiv, Lee Gethings, Jim Langridge, Karine Adel-Patient, Hervé Bernard, Ivona Barcievic-Jones, Raditsa Sokolova, Rumyana Yankova, Mariya Ivanovska, Marianna Murdjeva, Tatyana Popova, Svetlan Dermendzhiev, Martin Karjalainen, Ulrike Lehnigk, Duncan Brown, Julie C. Locklear, Julie Locklear, Ioana Maris, Jonathan Hourihane, Cristina Ornelas, Joana Caiado, Manuel Branco Ferreira, Manuel Pereira-Barbosa, Yolanda Puente, Juan Carlos Daza, Francisco Javier Monteseirin, Natalia Ukleja-Sokolowska, Ewa Gawronska-Ukleja, Magdalena Zbikowska-Gotz, Zbigniew Bartuzi, Lukasz Sokolowski, Aine Adams, Bernard Mahon, Karen English, Nelly Gourdon-Dubois, Laetitia Sellam, Bruno Pereira, Elodie Michaud, Khaled Messaoudi, Bertrand Evrard, Jean-Luc Fauquert, Francisca Palomares, Gador Gomez, Maria Jose Rodriguez, Luisa Galindo, Ana Molina, Lorella Paparo, Maurizio Mennini, Rosita Aitoro, Adam Wawrzeńczyk, Michał Przybyszewski, Anna Wawrzeńczyk, Hulya Ercan Sarıcoban, Meltem Ugras, Zerrin Yalvac, Bertine M. J. Flokstra-de Blok, J. L. van der Velde, Andrea Vereda, Clara Ippolito, Amaranta Traversa, Daniela Adriano, Daniela Manila Bianchi, Silvia Gallina, Lucia Decastelli, Melina Makatsori, Anne Miles, Sonja Posega Devetak, Iztok Devetak, Soraya Ainad Tabet, Jeanette Fisker Trandbohus, Pernille Winther, Hans-Jørgen Malling, Kirsten Skamstrup Hansen, Lene Heise Garvey, Chia-Chi Wang, Yin-Hua Cheng, Chun-Wei Tung, Mariola Dietrich, Ingo Marenholz, Birgit Kalb, Sarah Grosche, Katharina Blümchen, Rupert Schlags, Mareike Price, Sylke Rietz, Jorge Esparza-Gordillo, Susanne Lau, Young-Ae Lee, Ali Almontasheri, Mohammad Al Bahkali, Sahar Elshorbagi, Abdullah Alfhaid, Mashary Altamimi, Eman Madbouly, Hassan Al-Dhekri, Rand K. Arnaout, Maria Basagaña, Sira Miquel, Borja Bartolomé, Bettina Brix, Stefanie Rohwer, Sandra Brandhoff, Alena Berger, Waltraud Suer, Alf Weimann, Cristina Bueno, Laura Martín-Pedraza, Sara Abián, Pablo San Segundo-Acosta, Juan Carlos López-Rodríguez, Rodrigo Barderas, Eva Batanero, Javier Cuesta-Herranz, María Teresa Villalba, Magna Correia, Filipe Benito-Garcia, Cristina Arêde, Susana Piedade, Mário Morais-Almeida, James Hindley, Ross Yarham, Anna Kuklinska-Pijanka, David Gillick, Karine Patient, Martin D. Chapman, Katrine L. Bøgh, Ana Miranda, Eugénia Matos, Anna Sokolova, Huan Rao, Ivona Baricevic-Jones, Frances Smith, Wentong Xue, Helga Magnusdottir, Anna G. Vidarsdottir, Sigrun Lund, Anders Blom Jensen, Bjorn R. Ludviksson, Reyna Simon, Robert Elfont, Sean Bennett, Robert Voyksner, Maria de Lurdes Torre, Songül Yürek, Margaretha A. Faber, Annick Bastiaensen, Evelyne Mangodt, Athina van Gasse, Ine Decuyper, Vito Sabato, Margo M. Hagendorens, Chris H. Bridts, Luc S. De Clerck, Didier Ebo, Susanne Schwarz, Mandy Ziegert, Saskia Albroscheit, Christian Schwager, Skadi Kull, Jochen Behrends, Niels Röckendorf, Frauke Schocker, Andreas Frey, Arne Homann, Wolf-Meinhard Becker, Uta Jappe, Nesrine Zaabat, Sylvia Osscini, Chantal Agabriel, Benoît Sterling, Ania Carsin, Valérie Liabeuf, Monica Maćków, Alina Zbróg, Monica Bronkowska, Justine Courtois, Romy Gadisseur, Catherine Bertholet, Pierre Lukas, Etienne Cavalier, Philippe Delahaut, Birgit Quinting, Margareta Brandt Gertmo, Ewa Ternesten Hasseus, Vladyslava Barzylovych, Júlio Oliveira, Luis F. Ensina, Carolina S. Aranda, Leire Dopazo, Rebeca Lopez, Raquel Perez, Laura Santos-Diez, Agurtzane Bilbao, Juan Miguel Garcia, Ignacio García Núñez, María Ángeles Algaba Mármol, María José Barasona Villarejo, José Antonio Bácter Martos, Marina Suárez Vergara, José María Ignacio García, Agata Michalska, Grzegorz Sergiejko, Robert Zacniewski, Ileana-Maria Ghiordanescu, Cristina Deaconu, Mihaela Popescu, Roxana Silvia Bumbacea, Alkerta Ibranji, Elida Nikolla, Gjustina Loloci, Nanna Juel-Berg, Lau Fabricius Larsen, Lars Kjaergaard Poulsen, João Marcelino, Ricardo Prata, Ana Célia Costa, Fátima Duarte, Marta Neto, Jennifer Santos, Luís Câmara Pestana, Daniel Sampaio, Paola Minale, Paola Dignetti, Donatella Bignardi, Irena Nedelea, Florin-Dan Popescu, Mariana Vieru, Florin-Adrian Secureanu, Carmen Saviana Ganea, Miguel Vieira, José Pedro Moreira Silva, Timothy Watts, Sophia Watts, Marta Lomikovska, Marina Peredelskaya, Natalia Nenasheva, Ivana Filipovic, Zorica Zivkovic, Djordje Filipovic, Jennette Higgs, Amena Warner, and Carla Jones

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2017
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6. Non-Digestible Oligosaccharides Can Suppress Basophil Degranulation in Whole Blood of Peanut-Allergic Patients

Author

Simone M. Hayen, Constance F. den Hartog Jager, André C. Knulst, Edward F. Knol, Johan Garssen, Linette E. M. Willemsen, and Henny G. Otten

Subjects
basophil degranulation, food allergy, galectin-9, immunomodulation, non-digestible oligosaccharides, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundDietary non-digestible oligosaccharides (NDOs) have a protective effect against allergic manifestations in children at risk. Dietary intervention with NDOs promotes the colonization of beneficial bacteria in the gut and enhances serum galectin-9 levels in mice and atopic children. Next to this, NDOs also directly affect immune cells and low amounts may reach the blood. We investigated whether pre-incubation of whole blood from peanut-allergic patients with NDOs or galectin-9 can affect basophil degranulation.MethodsHeparinized blood samples from 15 peanut-allergic adult patients were pre-incubated with a mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS), scFOS/lcFOS, or galectin-9 (1 or 5 µg/mL) at 37°C in the presence of IL-3 (0.75 ng/mL). After 2, 6, or 24 h, a basophil activation test was performed. Expression of FcεRI on basophils, plasma cytokine, and chemokine concentrations before degranulation were determined after 24 h.ResultsPre-incubation with scGOS/lcFOS, scFOS/lcFOS, or galectin-9 reduced anti-IgE-mediated basophil degranulation. scFOS/lcFOS or 5 µg/mL galectin-9 also decreased peanut-specific basophil degranulation by approximately 20%, mainly in whole blood from female patients. Inhibitory effects were not related to diminished FcεRI expression on basophils. Galectin-9 was increased in plasma after pre-incubation with scGOS/lcFOS, and both NDOs and 5 µg/mL galectin-9 increased MCP-1 production.Conclusion and clinical relevanceThe prebiotic mixture scFOS/lcFOS and galectin-9 can contribute to decreased degranulation of basophils in vitro in peanut-allergic patients. The exact mechanism needs to be elucidated, but these NDOs might be useful in reducing allergic symptoms.

Published
2018
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7. The immunological phenotype of rituximab-sensitive chronic graft-versus-host disease: a phase II study

Author

Suzanne van Dorp, Henrike Resemann, Liane te Boome, Floor Pietersma, Debbie van Baarle, Frits Gmelig-Meyling, Roel de Weger, Eefke Petersen, Monique Minnema, Henk Lokhorst, Saskia Ebeling, Scott J.P. Beijn, Edward F. Knol, Marijke van Dijk, Ellen Meijer, and Jürgen Kuball

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Chronic graft-versus-host disease is the major long-term complication after allogeneic stem cell transplantation with a suboptimal response rate to current treatments. Therefore, clinical efficacy and changes in lymphocyte subsets before and after rituximab treatment were evaluated in a prospective phase II study in patients with steroid-refractory chronic graft-versus-host disease. Overall response rate was 61%. Only responding patients were found to have increased B-cell numbers prior to treatment. B cells had a naïve-antigen-presenting phenotype and were mainly CD5 negative or had a low CD5 expression. Normal B-cell homeostasis was reestablished in responding patients one year after ritxumab treatment and associated with a significant decline in skin-infiltrating CD8+ T cells, suggesting that host B cells play a role in maintaining pathological CD8+ T-cell responses. Imbalances in B-cell homeostasis could be used to identify patients a priori with a higher chance of response to rituximab treatment (Eudra-CT 2008-004125-42).

Published
2011
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8. Unraveling heterogeneity in pediatric atopic dermatitis: Identification of serum biomarker based patient clusters

Author

Daphne S. Bakker, Marjolein S. de Bruin-Weller, Judith L. Thijs, Marlies de Graaf, Stefan Nierkens, Edward F. Knol, Eveline M. Delemarre, Julia Drylewicz, and Femke van Wijk

Subjects
Male, Oncology, medicine.medical_specialty, Adolescent, Immunology, Severity of Illness Index, Dermatitis, Atopic, Disease severity, Serum biomarkers, Internal medicine, medicine, Humans, Immunology and Allergy, Child, Retinol binding protein 4, biology, business.industry, Infant, Newborn, Infant, T-Lymphocytes, Helper-Inducer, Atopic dermatitis, medicine.disease, Persistent Disease, Child, Preschool, biology.protein, Biomarker (medicine), Female, Personalized medicine, Age of onset, business, Biomarkers
Abstract

Background Increasing evidence shows that pediatric atopic dermatitis (AD) differs from adult AD on a biologic level. Broad biomarker profiling across a wide range of ages of pediatric patients with AD is lacking. Objective Our aim was to identify serum biomarker profiles in children with AD aged 0 to 17 years and compare these profiles with those previously found in adults with AD. Methods Luminex multiplex immunoassays were used to measure 145 biomarkers in serum from 240 children with AD (aged 0-17 years). Principal components analysis followed by unsupervised k-means clustering were performed to identify patient clusters. Patients were stratified into age groups (0-4 years, 5-11 years, and 12-17 years) to assess association between age and cluster membership. Results Children aged 0 to 4 years had the highest levels of TH1 cell–skewing markers and lowest levels of TH17 cell–related markers. TH2 cell–related markers did not differ significantly between age groups. Similar to the pattern in adults, cluster analysis identified 4 distinct pediatric patient clusters (TH2 cell/retinol–dominant, skin-homing–dominant, TH1 cell/TH2 cell/TH17 cell/IL-1–dominant, and TH1 cell/IL-1/eosinophil–inferior clusters). Only the TH1 cell/TH2 cell/TH17 cell/IL-1–dominant cluster resembled 1 of the previously identified adult clusters. Although no association with age or age of onset seemed to be found, disease severity was significantly associated with the skin-homing–dominant cluster. Conclusion Four distinct patient clusters based on serum biomarker profiles could be identified in a large cohort of pediatric patients with AD, of which 1 was similar to previously identified adult clusters. The identification of endotypes driven by distinct underlying immunopathologic pathways might be useful to define pediatric patients with AD who are at risk of persistent disease and may necessitate different targeted treatment approaches.

Published
2022

9. Management of anaphylaxis due to COVID-19 vaccines in the elderly

Author

Paulo Augusto Moreira Camargos, Radolslaw Gawlik, Mirko Petrovic, Gunter J. Sturm, Kristof Nekam, Sergio Bonini, Zhanat Ispayeva, Marilyn Urrutia Pereira, Jean Bousquet, Antti Lauerma, Menachem Rottem, Arzu Yorgancioglu, Hubert Blain, Antonio Cherubini, Mário Morais-Almeida, Nathalie Salles, Charlotte G. Mortz, Sylwia Smolinska, Davor Plavec, A. Bedbrook, Torsten Zuberbier, Helga Kraxner, M. Beatrice Bilò, Sinthia Bosnic-Anticevich, Gaëtan Gavazzi, Finbarr C. Martin, Alvaro A. Cruz, K. S. Bennoor, Isabella Annesi-Maesano, Mohamed H. Shamji, Karin Hoffmann-Sommergruber, Marina Atanaskovic-Markovic, Carsten Bindslev-Jensen, Lan Tt Le, Isabel Skypala, Ana Todo-Bom, Vincenzo Patella, Lorenzo Cecchi, Charlotte Suppli Ulrik, Oscar Palomares, Joaquin Sastre, Hans Jürgen Hoffmann, Knut Brockow, Eva Untersmayr, Martin Hrubisko, Bernadette Eberlein, Aziz Sheikh, Milan Sova, Osman M. Yusuf, Violeta Kvedariene, G. Walter Canonica, Dana Wallace, Ioana Agache, Milena Sokolowska, Jos M. G. A. Schols, Susan Waserman, Stéphanie Miot, Carla Irani, Regina E Roller-Winsberger, Michael Levin, Yves Rolland, Emma Montella, Bilun Gemicioglu, Bolesław Samoliński, Stefano Del Giacco, Madda lenaIllario, Yehia El-Gamal, Olga Lourenço, Jean-Christoph Roger J-P Caubet, Luisa Brussino, Marysia Recto, De Yun Wang, Igor Kaidashev, Renaud Louis, Antonino Romano, Mario E. Zernotti, Jacques Reynes, Pedro Carreiro-Martins, Alexandra F. Santos, Marek Niedoszytko, M. Gotua, Musa Khaitov, Thomas B. Casale, Andrea Matucci, Bernardo Sousa-Pinto, Rafael Stelmach, Dejan Dokic, Joana Vitte, Motohiro Ebisawa, Maria Teresa Ventura, Joaquim Mullol, Tomas Chivato, Petr Panzner, Oliver Pfaar, Sanna Toppila-Salmi, Ioanna Tsiligianni, Wytske Fokkens, Alessandra Vultaggio, H. Neffen, Juan Carlos Ivancevich, Ya-dong Gao, Anna Sediva, Maja Hofmann, Ana Maria Carriazo, João Fonseca, Marek Jutel, A. Benetos, Nhân Pham-Thi, Mona Al-Ahmad, Arunas Valiulis, Mihaela Zidarn, Elizabeth Angier, Yoshitaka Okamoto, Montserrat Fernandez-Rivas, Cezmi A. Akdis, Philip W. Rouadi, Olivier Guérin, John Farrell, Mikaela Odemyr, George Christoff, Vera Mahler, Claus Bachert, Edward F. Knol, Wienczyslawa Czarlewski, Robyn E O'Hehir, Victoria Cardona, Ludger Klimek, Tari Haahtela, Vincent Le Moing, Branislava Milenkovic, Carmen Rondon, Kaja Julge, Jolanta Walusiak-Skorupa, Nikolaos G. Papadopoulos, Aslı Gelincik, Markus Ollert, Piotr Kuna, Leyla Namazova-Baranova, Margitta Worm, Annick Barbaud, Elena Camelia Berghea, Todor A. Popov, Derek K. Chu, María José Torres, Faradiba Sarquis Serpa, Nicola Scichilone, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Gianni Passalacqua, Humboldt-Universität zu Berlin, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Humboldt University Of Berlin, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Transylvania University, Wrocław Medical University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Cagliari, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Università Politecnica delle Marche [Ancona] (UNIVPM), Medical Consulting Czarlewski, Universiti Putra Malaysia, University of Southampton, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Belgrade [Belgrade], Ghent University Hospital, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Dhaka Shishu Hospital [Bangladesh], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Odense University Hospital (OUH), Italian National Research Council, National Research Council [Italy] (CNR), The University of Sydney, Technische Universität München = Technical University of Munich (TUM), Università degli studi di Torino = University of Turin (UNITO), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), IRCCS Research Hospital, Milan, Vall d'Hebron University Hospital [Barcelona], Centro Hospitalar de Lisboa Central E.P.E, University of South Florida [Tampa] (USF), Geneva University Hospital (HUG), Azienda Usl Toscana centro [Firenze], Софийски университет = Sofia University, McMaster University [Hamilton, Ontario], State University of Bahia, Institute of Public Health of Republic of North Macedonia [Skopje], Ain Shams University (ASU), Sagamihara National Hospital [Kanagawa, Japan], Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Amsterdam UMC - Amsterdam University Medical Center, Universidade do Porto = University of Porto, Wuhan University [China], CHU Grenoble, Silesian University of Medicine, Istanbul Faculty of Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Centre Hospitalier Universitaire de Nice (CHU Nice), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Medizinische Universität Wien = Medical University of Vienna, Aarhus University [Aarhus], Oncology Institute of St Elisabeth, University of Naples Federico II = Università degli studi di Napoli Federico II, St Joseph University, Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Kazakh National Medical University, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Tartu University Institute of Clinical Medicine, Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Federal Medicobiological Agency [Moscow, Russian Federation], University Medical Center [Utrecht], Semmelweis University [Budapest], Medical University of Łódź (MUL), Vilnius University [Vilnius], University of Medicine and Pharmacy (VIETNAM), University of Cape Town, CHU Sart Tilman, Université de Liège, University of Beira Interior [Portugal] (UBI), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), uBibliorum, Ear, Nose and Throat, AII - Inflammatory diseases, CHU Montpellier, Wroclaw Medical University [Wrocław, Pologne], University of Bari Aldo Moro (UNIBA), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sagamihara National Hospital, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Toulouse [Toulouse], RS: CAPHRI - R1 - Ageing and Long-Term Care, Health Services Research, Bousquet J., Agache I., Blain H., Jutel M., Ventura M.T., Worm M., Del Giacco S., Benetos A., Bilo B.M., Czarlewski W., Abdul Latiff A.H., Al-Ahmad M., Angier E., Annesi-Maesano I., Atanaskovic-Markovic M., Bachert C., Barbaud A., Bedbrook A., Bennoor K.S., Berghea E.C., Bindslev-Jensen C., Bonini S., Bosnic-Anticevich S., Brockow K., Brussino L., Camargos P., Canonica G.W., Cardona V., Carreiro-Martins P., Carriazo A., Casale T., Caubet J.-C., Cecchi L., Cherubini A., Christoff G., Chu D.K., Cruz A.A., Dokic D., El-Gamal Y., Ebisawa M., Eberlein B., Farrell J., Fernandez-Rivas M., Fokkens W.J., Fonseca J.A., Gao Y., Gavazzi G., Gawlik R., Gelincik A., Gemicioglu B., Gotua M., Guerin O., Haahtela T., Hoffmann-Sommergruber K., Hoffmann H.J., Hofmann M., Hrubisko M., Illario M., Irani C., Ispayeva Z., Ivancevich J.C., Julge K., Kaidashev I., Khaitov M., Knol E., Kraxner H., Kuna P., Kvedariene V., Lauerma A., Le L.T.T., Le Moing V., Levin M., Louis R., Lourenco O., Mahler V., Martin F.C., Matucci A., Milenkovic B., Miot S., Montella E., Morais-Almeida M., Mortz C.G., Mullol J., Namazova-Baranova L., Neffen H., Nekam K., Niedoszytko M., Odemyr M., O'Hehir R.E., Okamoto Y., Ollert M., Palomares O., Papadopoulos N.G., Panzner P., Passalacqua G., Patella V., Petrovic M., Pfaar O., Pham-Thi N., Plavec D., Popov T.A., Recto M.T., Regateiro F.S., Reynes J., Roller-Winsberger R.E., Rolland Y., Romano A., Rondon C., Rottem M., Rouadi P.W., Salles N., Samolinski B., Santos A.F., S Sarquis F., Sastre J., M. G. A. Schols J., Scichilone N., Sediva A., Shamji M.H., Sheikh A., Skypala I., Smolinska S., Sokolowska M., Sousa-Pinto B., Sova M., Stelmach R., Sturm G., Suppli Ulrik C., Todo-Bom A.M., Toppila-Salmi S., Tsiligianni I., Torres M., Untersmayr E., Urrutia Pereira M., Valiulis A., Vitte J., Vultaggio A., Wallace D., Walusiak-Skorupa J., Wang D.-Y., Waserman S., Yorgancioglu A., Yusuf O.M., Zernotti M., Zidarn M., Chivato T., Akdis C.A., Zuberbier T., Klimek L., HUS Inflammation Center, University of Helsinki, and Department of Dermatology, Allergology and Venereology

Subjects
Male, Allergy, Pediatrics, Eaaci Position Paper, COVID-19 vaccines, older (adults, GUIDELINES, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Immunology and Allergy, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Geriatrics, MESH: Aged, RISK, Vaccines, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, people), EPINEPHRINE, Epinephrine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, COVID -19 vaccines, Anaphylaxis, medicine.drug, older (adults/people), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), MESH: Covid-19, MESH: Epinephrine, Immunology, adrenaline, anaphylaxis, Aged, COVID-19 Vaccines, Humans, SARS-CoV-2, COVID-19, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes mellitus, Anaphylaxis/etiology, MESH: SARS-CoV-2, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, COVID‐19 vaccines, Older - Adults/people, Asthma, MESH: Humans, business.industry, adrenaline, anaphylaxis, COVID-19 vaccines, older (adults/people), medicine.disease, Obesity, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: Anaphylaxis, Older, 3121 General medicine, internal medicine and other clinical medicine, business, MESH: Covid-19 vaccines, 030215 immunology
Abstract

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Published
2021

10. ARIA‐EAACI statement on severe allergic reactions to COVID‐19 vaccines – An EAACI‐ARIA Position Paper

Author

Ioana Agache, Eva Untersmayr, Torsten Zuberbier, Jean Bousquet, Karin Hoffmann-Sommergruber, Mübeccel Akdis, María José Torres, Stefano Del Giacco, Cezmi A. Akdis, G. Walter Canonica, Anna Bedbrook, Ludger Klimek, Marek Jutel, Edward F. Knol, Margitta Worm, Tomas Chivato, Mohamed H. Shamji, Johannes Ring, Jürgen Schwarze, Liam O'Mahony, University of Zurich, and Klimek, Ludger

Subjects
0301 basic medicine, Allergy, medicine.medical_specialty, COVID-19 Vaccines, Immunology, Population, 610 Medicine & health, Herd immunity, 03 medical and health sciences, 0302 clinical medicine, 10183 Swiss Institute of Allergy and Asthma Research, medicine, Humans, Immunology and Allergy, Medical history, education, Intensive care medicine, Adverse effect, BNT162 Vaccine, Asthma, Vaccines, 2403 Immunology, education.field_of_study, SARS-CoV-2, business.industry, COVID-19, medicine.disease, Vaccination, 030104 developmental biology, 030228 respiratory system, 2723 Immunology and Allergy, business, Anaphylaxis
Abstract

Coronavirus disease 2019 (COVID-19) vaccine BNT162b2 received approval and within the first few days of public vaccination several severe anaphylaxis cases occurred. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and concerns raised for severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerges. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as the exclusion of all these patients from vaccination may have a significant impact on reaching the goal of population immunity. Health care practitioners vaccinating against COVID-19 are required to be sufficiently prepared to recognise and treat anaphylaxis properly with the ability to administer adrenaline. A mandatory observation period after vaccine administration of at least 15 minutes for all individuals should be followed. The current data has not shown any higher risk for patients suffering from allergic rhinitis or asthma and this message should be clearly stated by physicians to give our patients trust. The benefit of the vaccination clearly outweighs the risk of severe COVID-19 development including the more than 30% of the population suffering from allergic diseases.

Published
2021

11. COVID-19 pandemic

Author

W. J. Fokkens, Jürgen Schwarze, Cezmi A. Akdis, J Mullol, W. Czarlewski, Claudia Traidl-Hoffmann, Claus Bachert, D. Larenas-Linnemann, Tomas Chivato, M. Gotua, Mateo Bonini, Ludger Klimek, Vincenzo Patella, A. A. Cruz, Stephanie Dramburg, Kari C. Nadeau, H W Fritsch, K. Ohta, Thomas Eiwegger, Robert M. Naclerio, Antti Lauerma, A. Yorgancioglu, Aslı Gelincik, Piotr Kuna, Oliver Pfaar, Carmen Riggioni, Violeta Kvedariene, Markus Ollert, Sinthia Bosnic-Anticevich, V. Cardona, S. Del Giacco, Sanna Toppila-Salmi, Helen A. Brough, Heimo Breiteneder, Valérie Hox, B. Samolinski, Zuzana Diamant, G.W. Canonica, Lihong Zhang, María José Torres, Y. Okamoto, Liam O'Mahony, Radosław Gawlik, Jolanta Walusiak-Skorupa, Sharon Chinthrajah, Winfried Rief, T. Haatela, M. Morais-Almeida, Ioana Agache, Manfred Schedlowski, I Skypala, R. Brehler, D. Y. Wang, João Fonseca, I. J. Ansotegui, Robyn E O'Hehir, Oscar Palomares, Charlotte G. Mortz, J. C. Ivancevich, C. Suppli Ulrik, M. T. Ventura, P M Matricardi, S Untersmayr, Gabrielle L. Onorato, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Vanitha Sampath, Arũnas Valiulis, Marek Jutel, Luisa Brussino, Pedro Carreiro-Martins, Jean Bousquet, Nikolaos G. Papadopoulos, A. Bedbrook, Torsten Zuberbier, Karin Hoffmann-Sommergruber, Edward F. Knol, Ear, Nose and Throat, AII - Inflammatory diseases, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service d'oto-rhino-laryngologie, Philipps Universität Marburg = Philipps University of Marburg, Allergologie, Stimm und Sprachstörungen [Wiesbaden, Germany], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], University of Wrocław [Poland] (UWr), ALL-MED, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Medizinische Universität Wien = Medical University of Vienna, Stanford University, Skane University Hospital [Malmo], Lund University [Lund], Charles University [Prague] (CU), University Medical Center Groningen [Groningen] (UMCG), Univ Toronto, Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Mol Med, Toronto, ON M5G 0A4, Canada, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Amsterdam UMC - Amsterdam University Medical Center, Alfred Health, Victoria University [Melbourne], University College Cork (UCC), Sean N. Parker Center for Allergy and Asthma Research [Stanford], Stanford Medicine, Stanford University-Stanford University, University Clinics of Essen, University of Essen, Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Helmholtz Zentrum München = German Research Center for Environmental Health, University Hospital Augsburg, National University of Singapore (NUS), Beijing Tongren Hospital, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Evelina London Children's Hospital, King‘s College London, CEU-San Pablo University and HM-Hospitals School of Medicine, University of Cagliari, Medical University of Silesia (SUM), Istanbul University, Cliniques Universitaires Saint-Luc [Bruxelles], University Medical Center [Utrecht], Helsinki University Central Hospital, University of Helsinki, Odense University Hospital (OUH), Luxembourg Institute of Health (LIH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital Sant Joan de Déu [Barcelona], Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], University of Edinburgh, NHS Foundation Trust [London], The Royal Marsden, Nofer Institute of Occupational Medicine (NIOM), Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Woolcock Institute of Medical Research [Sydney], The University of Sydney, University of Turin, Mauriziano Umberto I Hospital, Humanitas University [Milan] (Hunimed), Vall d'Hebron University Hospital [Barcelona], Hospital de Dona Estefania, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Federal University of Bahia School of Medicine, Global Alliance Against Chronic Respiratory Diseases (GARD-WHO), Medical Consulting Czarlewski, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, MEDIDA, Lda, David Tvildiani Medical University (DTMU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Barlicki University Hospital, Vilnius University [Vilnius], Hospital Medica Sur [Mexico City, Mexico], Pantai Hospital [Kuala Lumpur], Hospital CUF Descobertas, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Epidemiología y Salud Pública (CIBERESP), Johns Hopkins University School of Medicine [Baltimore], Fukujuji Hospital, Tokyo National Hospital, Chiba Rosai Hospital, Chiba University Hospital, Royal Manchester Children's Hospital, University of Manchester [Manchester], General Children's Hospital of Athens P & A Kyriakou, 'Santa Maria della Speranza' Hospital, Centro Hospitalar e Universitário [Coimbra], Coimbra Institute for Clinical and Biomedical Research [Coimbra, Portugal] (iCBR - Faculty of Medicine), University of Coimbra [Portugal] (UC), Medical University of Warsaw - Poland, Hvidovre Hospital, University of Copenhagen = Københavns Universitet (UCPH), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Manisa Celal Bayar University, Transilvania University of Brasov, Salvy-Córdoba, Nathalie, Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center

Subjects
0301 basic medicine, viruses, Eaaci Position Paper, Medizin, Cochrane Library, GUIDELINES, FOOD ALLERGY, allergen immunotherapy, allergy clinic, anaphylaxis, asthma, clinical trials, COVID-19, Position Paper, psychological impact, SARS-CoV-2, Allergists, Health Personnel, Humans, Hypersensitivity, Information Technology, Patient Care Team, Triage, SARS‐CoV‐2, DESENSITIZATION, 0302 clinical medicine, MESH: Patient Care Team, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HDE ALER, Pandemic, Health care, Immunology and Allergy, ATOPIC-DERMATITIS, MESH: COVID-19, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, allergen immunotherapy (AIT), virus diseases, DRUG HYPERSENSITIVITY REACTIONS, 3. Good health, INFECTIONS, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Triage, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Allergen immunotherapy, medicine.medical_specialty, MESH: Information Technology, MESH: Hypersensitivity, Immunology, education, MEDLINE, DIAGNOSIS, psychological COVID, 03 medical and health sciences, MESH: Allergists, COVID‐19, medicine, MESH: SARS-CoV-2, ddc:610, RHINOSINUSITIS, MESH: Humans, business.industry, Clinical trial, Coronavirus, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Position paper, MESH: Health Personnel, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

BackgroundThe Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.MethodThe scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.ResultsBased on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.ConclusionsThis international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.

Published
2021

12. Confirmation of multiple endotypes in atopic dermatitis based on serum biomarkers

Author

Judith L. Thijs, Eveline M. Delemarre, Jorien van der Schaft, Marjolein S. de Bruin-Weller, Edward F. Knol, Stefan Nierkens, Julia Drylewicz, Femke van Wijk, Barbara Giovannone, and Daphne S. Bakker

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Immunology, Eczema Area and Severity Index, Dermatitis, Atopic, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Serum biomarkers, Internal medicine, medicine, Cluster (physics), Humans, Immunology and Allergy, business.industry, Models, Immunological, Atopic dermatitis, Middle Aged, medicine.disease, 030228 respiratory system, Cohort, Biomarker (medicine), Female, Personalized medicine, business, Biomarkers
Abstract

Background Atopic dermatitis (AD) is a highly heterogeneous disease, both clinically and biologically, whereas patients are still being treated according to a “one-size-fits-all” approach. Stratification of patients into biomarker-based endotypes is important for future development of personalized therapies. Objective Our aim was to confirm previously defined serum biomarker-based patient clusters in a new cohort of patients with AD. Methods A panel of 143 biomarkers was measured by using Luminex technology in serum samples from 146 patients with severe AD (median Eczema Area and Severity Index = 28.3; interquartile range = 25.2-35.3). Principal components analysis followed by unsupervised k-means cluster analysis of the biomarker data was used to identify patient clusters. A prediction model was built on the basis of a previous cohort to predict the 1 of the 4 previously identified clusters to which the patients of our new cohort would belong. Results Cluster analysis identified 4 serum biomarker–based clusters, 3 of which (clusters B, C, and D) were comparable to the previously identified clusters. Cluster A (33.6%) could be distinguished from the other clusters as being a “skin-homing chemokines/IL-1R1–dominant” cluster, whereas cluster B (18.5%) was a “TH1/TH2/TH17-dominant” cluster, cluster C (18.5%) was a “TH2/TH22/PARC-dominant” cluster, and cluster D (29.5%) was a “TH2/eosinophil-inferior” cluster. Additionally, by using a prediction model based on our previous cohort we accurately assigned the new cohort to the 4 previously identified clusters by including only 10 selected serum biomarkers. Conclusion We confirmed that AD is heterogeneous at the immunopathologic level and identified 4 distinct biomarker-based clusters, 3 of which were comparable with previously identified clusters. Cluster membership could be predicted with a model including 10 serum biomarkers.

Published
2021

13. T-cell subsets in the skin and their role in inflammatory skin disorders

Author

Inge Kortekaas Krohn, Femke van Wijk, Jan Gutermuth, Cleo Goyvaerts, Karine Breckpot, Edward F. Knol, Joeri L. Aerts, Dermatology, Neuro-Aging & Viro-Immunotherapy, Pharmaceutical and Pharmacological Sciences, Basic (bio-) Medical Sciences, Laboratory of Molecullar and Cellular Therapy, Artificial Intelligence supported Modelling in clinical Sciences, Gerontology, and Skin function and permeability

Subjects
skin, medicine.medical_treatment, T cell, Immunology, Skin Diseases, DISEASE, Allergic inflammation, Chemokine receptor, T-Lymphocyte Subsets, melanoma, Humans, Immunology and Allergy, Medicine, Receptor, Transcription factor, Inflammation, business.industry, Acquired immune system, Cytokine, medicine.anatomical_structure, Health, Cytokines, business, Function (biology)
Abstract

T lymphocytes (T cells) are major players of the adaptive immune response. Naive T cells are primed in the presence of cytokines, leading to polarization into distinct T-cell subsets with specific functions. These subsets are classified based on their T-cell receptor profile, expression of transcription factors, surface cytokine and chemokine receptors, and their cytokine production, which together determine their specific function. This review provides an overview of the various T-cell subsets and their function in several inflammatory skin disorders ranging from allergic inflammation to skin tumors. Moreover, we highlight similarities of T-cell responses across different skin disorders, demonstrating the presence of similar and opposing functions for the different T-cell subsets. Finally, we discuss the effects of currently available and promising therapeutic approaches to harness T cells in inflammatory skin diseases for which efficacy next to unwanted side effects provide new insights into the pathophysiology of skin disorders.

Published
2022

14. Handling of allergen immunotherapy in the COVID‐19 pandemic: An ARIA‐EAACI statement

Author

Erik Melén, Edward F Knol, Karin Hoffmann-Sommergruber, N. Khaltaev, Bolesław Samoliński, Cezmi A. Akdis, Claus Bachert, Hui Du, Sinthia Bosnic-Anticevich, Maria Teresa Ventura, Ruby Pawankar, Mohamed H. Shamji, Mübeccel Akdis, Ken Ohta, Joaquim Mullol, Jean Bousquet, Robert M. Naclerio, Ioana Agache, Tari Haahtela, Arunas Valiulis, Sanna Toppila-Salmi, I. J. Ansotegui, J. C. Ivancevich, Oliver Pfaar, Giorgio Walter Canonica, Gabrielle L. Onorato, Ya-dong Gao, Alvaro A. Cruz, Anna Bedbrook, Stefano Del Giacco, Yoshitaka Okamoto, Marek Jutel, P. M. Matricardi, Nikos G Papadopoulos, Wiencyslawa Czarlewski, João Fonseca, D. Larenas-Linnemann, Piotr Kuna, Tomas Chivato, Arzu Yorgancioglu, Jürgen Schwarze, Torsten Zuberbier, Ludger Klimek, Liam O'Mahony, Center for Rhinology and Allergology, Wiesbaden, Germany, Department of Clinical Immunology, Wrocław Medical University, ALL-MED Medical Research Institute, Poland, Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland, Universitätsmedizin Berlin, Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, CharitéHumboldt-Universität zu BerlinBerlin, Germany, University Hospital, Montpellier, France, MACVIA-France, Montpellier, France, Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium, Transylvania University BrasovBrasov, Romania, Department of Allergy and Immunology, Hospital Quirónsalud Bizkaia, Erandio, Spain, Woolcock Institute of Medical Research, University of Sydney and Woolcock Emphysema Centre and Sydney Local Health District, NSW, Australia, Personalized Medicine Clinic Asthma & Allergy, Humanitas University, Humanitas Research Hospital, Rozzano, Milan, Italy, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Rozzano, MI, Italy, School of Medicine, University CEU San PabloMadrid, Spain, ProAR - Nucleo de Excelencia em Asma, Federal University of Bahia, Brasil and WHO GARD Planning Group, Salvador, Brazil, Medical Consulting Czarlewski, Montpellier, France, Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital 'Duilio Casula', University of Cagliari, Cagliari, Italy, Department of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College, University of Science and Technology, Wuhan, Hubei, China, Center for research in health technologies and information systems- CINTESIS, Universidade do PortoPorto, Portugal, Allergy Unit, Instituto CUF Porto e Hospital CUF PortoPorto, Portugal, Health Information and Decision Sciences Department - CIDES, Faculdade de Medicina, Universidade do PortoPorto, Portugal, Faculdade de Medicina da Universidade do PortoPorto, Portugal, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland, Department of Pathophysiology and Allergy Research, Medical University of ViennaVienna, Austria, Servicio de Alergia e Immunologia, Clinica Santa Isabel, Aires, Argentina, Geneva, Switzerland, Departments of Immunology and Dermatology/Allergology, University Medical CenterUtrecht, Netherlands, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and HospitalMéxico City, Mexico, Institute of Environmental Medicine, Karolinska Institutet and Sachs' Children's HospitalStockholm, Sweden, Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Johns Hopkins School of Medicine, Baltimore, MD, United States, National Hospital Organization, Tokyo National HospitalTokyo, Japan, Dept of Otorhinolaryngology, Chiba University HospitalChiba, Japan, Departments of Medicine and Microbiology, University College Cork, Cork, Ireland, Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of ManchesterManchester, United Kingdom, Department of Pediatrics, Nippon Medical SchoolTokyo, Japan, Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Germany, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Poland, Centre for Inflammation Research, Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom, Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London. Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom, University of Bari Medical School, Unit of Geriatric ImmunoallergologyBari, Italy, Vilnius University, Faculty of Medicine, Institute of Clinical Medicine &, Institute of Health SciencesVilnius, Lithuania, European Academy of Paediatrics, Brussels, Belgium, Celal Bayar University, Department of PulmonologyManisa, Turkey, Charité - Universitätsmedizin BerlinBerlin, Germany, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Comprehensive Allergy-Centre, Department of Dermatology and AllergyBerlin, Germany, Klimek, Ludger, Jutel, Marek, Akdis, Cezmi, Bousquet, Jean, Akdis, Mübeccel, Bachert, Clau, Agache, Ioana, Ansotegui, Ignacio, Bedbrook, Anna, Bosnic-Anticevich, Sinthia, Canonica, Giorgio W, Chivato, Toma, Cruz, Alvaro A, Czarlewski, Wiencyslawa, Giacco, Stefano Del, Du, Hui, Fonseca, Joao A, Gao, Yadong, Haahtela, Tari, Hoffmann-Sommergruber, Karin, Ivancevich, Juan-Carlo, Iaccarino, Guido, Khaltaev, Nikolai, Knol, Edward F, Kuna, Piotr, Larenas-Linnemann, Desiree, Melen, Erik, Mullol, Joaquim, Naclerio, Robert, Ohta, Ken, Okamoto, Yoshitaka, O'Mahony, Liam, Onorato, Gabrielle L, Papadopoulos, Nikos G, Pawankar, Ruby, Pfaar, Oliver, Samolinski, Boleslaw, Schwarze, Jurgen, Toppila-Salmi, Sanna, Shamji, Mohamed H, Ventura, Maria Teresa, Valiulis, Aruna, Yorgancioglu, Arzu, Matricardi, Paolo, Zuberbier, Torsten, Department of Dermatology, Allergology and Venereology, HUS Inflammation Center, and Department of Pathology

Subjects
0301 basic medicine, Allergy, Eaaci Position Paper, CD8-Positive T-Lymphocytes, Social life, 0302 clinical medicine, clinical immunotherapy, Pandemic, Immunology and Allergy, Infection control, AIT, Treatment options, 3. Good health, Coronavirus Infections, Allergen immunotherapy, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Immunology, Eaaci Position Papers, MECHANISMS, Betacoronavirus, 03 medical and health sciences, Allergists, Th2 Cells, VACCINES, allergy treatment, medicine, VENOM ALLERGY, Humans, Intensive care medicine, Pandemics, Infection Control, Sublingual Immunotherapy, immunotherapy vaccines and mechanisms, SARS-CoV-2, business.industry, COVID-19, Immunoglobulin E, medicine.disease, Rhinitis, Allergic, Asthma, Allergen-specific immunotherapy, Coronavirus, Eosinophils, 030104 developmental biology, Immunoglobulin M, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, business
Abstract

The current COVID-19 pandemic influences many aspects of personal and social interaction, including patient contacts with health care providers and the manner in which allergy care is provided and maintained. Allergen-specific immunotherapy (AIT) is one of the most important treatment options for IgE-mediated allergies and is based on inducing an appropriate immune response in the allergic patient. This manuscript outlines the EAACI recommendations regarding AIT during the COVID-19 pandemic and aims at supporting allergists and all physicians performing AIT in their current daily practice with clear recommendations on how to perform treatment during the pandemic and in SARS-CoV-2 infected patients.

Published
2020

15. Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemiea, b, c

Author

F. Hentges, Peter Schmid-Grendelmeier, Davide Firinu, Mübecell Akdis, Randolf Brehler, Adam Chaker, Joachim Saloga, Alexander R. Rosenkranz, Eva Untersmayr, Wolfgang Czech, Jörg Kleine-Tebbe, Christian Vogelberg, Torsten Zuberbier, Verena Niederberger-Leppin, Karin Hoffmann-Sommergruber, Eckard Hamelmann, Tomas Chivato, Thomas Werfel, Zsolt Szépfalusi, Wolfram Hötzenecker, Marek Jutel, Edward F. Knol, Stephanie Korn, Jürgen Schwarze, Thilo Jakob, Stefan Wöhrl, Susanne Lau, Markus Ollert, Christian Taube, Thomas Keil, J. Hagemann, P. Kauppi, Alexia Chatzipetrou, Ralph Mösges, Petra Staubach, P. V. Tomazic, Thomas Eiwegger, Laura Freudelsperger, Norbert Mülleneisen, Sevim Bavbek, Oliver Pfaar, Stefano Del Giacco, Uta Jappe, Uta Rabe, Johannes Ring, François Spertini, Werner Aberer, Karl-Christian Bergmann, Tilo Biedermann, Hans F. Merk, Jeroen Buters, Martin Wagenmann, Susan Chan, Antje Fink Wagner, Jean-Pierre Michel, Claus Rabe, Thomas Fuchs, Rudolf Valenta, Wolfgang Wehrmann, Otto Spranger, Roland Buhl, A. Vultaggio, Jean Bousquet, Katja Nemat, Regina Roller-Wirnsberger, Thomas Bieber, Ioana Agache, Marcus Maurer, Cezmi A. Akdis, Kirsten Jung, Wolfgang Schlenter, Apostolos Bossios, F. Horak, Isabella Pali-Schöll, L. Nicod, Ingrid Casper, N. Khaltaev, Andrea Matucci, Marco Idzko, Sven Becker, Akash Kothari, Ludger Klimek, Oscar Palomares, Erika Jensen-Jarolim, A. Kolios, Wolfgang Pohl, Claus Vogelmeier, P. M. Matricardi, Ulf Darsow, Holger Wrede, Margitta Worm, and Liam O´mahony

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology and Allergy, Medicine, business, Virology
Published
2020

16. Dupilumab is very effective in a large cohort of difficult-to-treat adult atopic dermatitis patients

Author

Cynthia C. A. van Amerongen, Marie L A Schuttelaar, Lieneke F.M. Ariëns, Tessa A. Kouwenhoven, Edward F. Knol, Evelien M Delemarre, Femke van Wijk, Deepak M.W. Balak, Julia Drylewicz, Judith L. Thijs, Marijke Kamsteeg, Jorien van der Schaft, Margreet L E Romeijn, Stefan Nierkens, Barbara Giovannone, Marjolein S. de Bruin-Weller, Daphne S. Bakker, and Public Health Research (PHR)

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Immunology, Antibodies, Monoclonal, Humanized, Placebo, Eczema Area and Severity Index, Dermatitis, Atopic, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Internal medicine, dupilumab, Anti-Allergic Agents, Humans, Medicine, Immunology and Allergy, Registries, daily practice, atopic dermatitis, PLACEBO, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], biomarkers, Dermatology Life Quality Index, Atopic dermatitis, Middle Aged, medicine.disease, Dupilumab, Treatment Outcome, 030104 developmental biology, 030228 respiratory system, Concomitant, Cohort, Biomarker (medicine), Female, disease severity, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

INTRODUCTION: Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce.OBJECTIVE: To study the effect of 16-week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate-severe AD in daily practice.METHODS: Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen-week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI-50 (Eczema Area and Severity Index) or EASI-75, as well as patient-reported outcomes measures (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty-one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16 weeks).RESULTS: In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult-to-treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI-50 and EASI-75 were achieved by 114 (86%) and 82 (62%) patients after 16 weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity-related serum biomarkers (TARC, PARC, periostin, and IL-22), eotaxin-1, and eotaxin-3 significantly decreased.CONCLUSION: Treatment with dupilumab significantly improved disease severity and decreased severity-related serum biomarkers in patients with very difficult-to-treat AD in a daily practice setting.

Published
2020

17. Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic

Author

Ludger Klimek, Oliver Pfaar, Margitta Worm, Thomas Eiwegger, Jan Hagemann, Markus Ollert, Eva Untersmayr, Karin Hoffmann-Sommergruber, Alessandra Vultaggio, Ioana Agache, Sevim Bavbek, Apostolos Bossios, Ingrid Casper, Susan Chan, Alexia Chatzipetrou, Christian Vogelberg, Davide Firinu, Paula Kauppi, Antonios Kolios, Akash Kothari, Andrea Matucci, Oscar Palomares, Zsolt Szépfalusi, Wolfgang Pohl, Wolfram Hötzenecker, Alexander R. Rosenkranz, Karl-Christian Bergmann, Thomas Bieber, Roland Buhl, Jeroen Buters, Ulf Darsow, Thomas Keil, Jörg Kleine-Tebbe, Susanne Lau, Marcus Maurer, Hans Merk, Ralph Mösges, Joachim Saloga, Petra Staubach, Uta Jappe, Klaus F. Rabe, Uta Rabe, Claus Vogelmeier, Tilo Biedermann, Kirsten Jung, Wolfgang Schlenter, Johannes Ring, Adam Chaker, Wofgang Wehrmann, Sven Becker, Laura Freudelsperger, Norbert Mülleneisen, Katja Nemat, Wolfgang Czech, Holger Wrede, Randolf Brehler, Thomas Fuchs, Peter-Valentin Tomazic, Werner Aberer, Antje-Henriette Fink-Wagner, Fritz Horak, Stefan Wöhrl, Verena Niederberger-Leppin, Isabella Pali-Schöll, Regina Roller-Wirnsberger, Otto Spranger, Rudolf Valenta, Mübecell Akdis, Paolo M. Matricardi, François Spertini, Nicolai Khaltaev, Jean-Pierre Michel, Larent Nicod, Peter Schmid-Grendelmeier, Marco Idzko, Eckard Hamelmann, Thilo Jakob, Thomas Werfel, Martin Wagenmann, Christian Taube, Erika Jensen-Jarolim, Stephanie Korn, Francois Hentges, Jürgen Schwarze, Liam O´Mahony, Edward F. Knol, Stefano del Giacco, Tomás Chivato Pérez, Jean Bousquet, Anna Bedbrook, Torsten Zuberbier, Cezmi Akdis, and Mared Jutel

Subjects
benralizumab, Allergy, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, General Engineering, COVID-19, mepolizumab, reslizumab, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, dupilumab, Immunology, Pandemic, omalizumab, General Earth and Planetary Sciences, Medicine, telemedicine, 030212 general & internal medicine, Current (fluid), business, Research Article, General Environmental Science
Abstract

Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for “social distancing” and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2. Materials and methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 – April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic. Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future. Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.

Published
2020

18. Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food: A first step in an initiative to better inform patients and avoid fatal allergic reactions, A GA²LEN position paper

Author

Giovanni Battista Pajno, Stefan Wöhrl, Sasho Stoleski, Caroline Nilsson, Mary Jane Marchisotto, Ronald van Ree, Carina Venter, Anna Nowak-Wegrzyn, Montserrat Fernandez-Rivas, Akio Tanaka, Barbara Rogala, Benjamin Kendziora, Michihiro Hide, Stefano Del Giacco, Katarina Stevanovic, Dragan Mijakoski, Enrico Heffler, Nikolaos G. Papadopoulos, Werner Aberer, Antoine Deschildre, Lisa A. Beck, Kate Grimshaw, M. Gotua, Torsten Zuberbier, Hugh A. Sampson, Marek Jutel, Mikela Odemyr, Carlo Lombardi, Erkka Valovirta, Antonella Cianferoni, Nicolette W. de Jong, Jovanka Karadzinska Bislimovska, Michael J. Cork, Christer Janson, Karin Hoffmann-Sommergruber, Gianenrico Senna, Jean Bousquet, Michael Makris, Carsten Bindslev-Jensen, Tamara Dörr, Joan Bartra, Ana Todo-Bom, Mika J. Mäkelä, Ulf Darsow, Margitta Worm, Richard Loh, Rosan Meyer, Giampaolo Ricci, Roy Gerth van Wijk, Audrey Dunn Galvin, Joaquim Mullol, M Alvaro, Alessandro Fiocchi, Zuotao Zhao, Stefania Arasi, Marta Ferrer, Norito Katoh, Philippe Bégin, Brigita Sitkauskiene, Sushil Paudel, Knut Brockow, Johannes Ring, Edward F. Knol, Susanne Lau, Gary W.K. Wong, Jordan Minov, Cristoforo Incorvaia, Marcus Maurer, Hasan Arshad, Fatih A Topal, Bright I Nwaru, Hania Szajewska, Andrew Bush, Tamar Kinaciyan, Adnan Custovic, Elizabeth Angier, O M Kurbacheva, Diana Deleanu, Harald Renz, Peter Smith, Motohiro Ebisawa, J. Grünhagen, Swen Malte John, Carla P. Jones, Barbara Ballmer-Weber, Ear, Nose and Throat, Experimental Immunology, AII - Inflammatory diseases, APH - Global Health, and APH - Personalized Medicine

Subjects
Food industry, Eggs, Immunology, Provocation test, Declaration, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Allergen, Food allergy, Food Labeling, Environmental health, anaphylaxis, Immunology and Allergy, Medicine, Ingestion, Animals, Humans, SDG 2 - Zero Hunger, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Meal, food allergy, business.industry, digestive, oral, and skin physiology, Allergens, medicine.disease, 3. Good health, nutrition, 030228 respiratory system, Food processing, business, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Food Hypersensitivity
Abstract

Background\ud \ud Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as “may contain traces of” is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin.\ud \ud \ud \ud Methods\ud \ud MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results.\ud \ud \ud \ud Results\ud \ud In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds.\ud \ud \ud \ud Conclusion\ud \ud Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement “this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product” for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.

Published
2021

19. Systemic and local evidence for complement involvement in chronic spontaneous urticaria

Author

Marijke R. van Dijk, Harmieke van Os-Medendorp, Edward F. Knol, Mignon T. van den Elzen, Henny G. Otten, Heike Röckmann, André C. Knulst, and Mehran Alizadeh Aghdam

Subjects
Pulmonary and Respiratory Medicine, skin, medicine.medical_specialty, Immunology, Omalizumab, Gastroenterology, Pathogenesis, urticaria, Immune system, blood, Internal medicine, medicine, Immunology and Allergy, complement, business.industry, Research, Papillary dermis, RC581-607, Peripheral blood, Complement system, Complement (complexity), omalizumab, Immunologic diseases. Allergy, Complement membrane attack complex, business, medicine.drug
Abstract

Background The pathogenesis of chronic spontaneous urticaria (CSU), including the mechanism of action of omalizumab, remain unclear. We hypothesized complement system involvement given the often fast clinical response induced by treatment, including omalizumab. Therefore, we assessed the role of various complement factors surrounding omalizumab treatment. Methods Thirty CSU patients (median age 42 [range 21–70]; 73 % female) with a median once daily Urticaria Activity Score over 7 days (UAS7) score at baseline of 31.5 points were enrolled. Treatment consisted of six administrations of 300 mg omalizumab every 4 weeks succeeded by a follow‐up period of 12 weeks. Four punch skin biopsies were taken per patient; at baseline from lesional skin, at baseline from nonlesional skin, and after 1 and 7 days from formerly lesional skin. Complement activity, including C1q, C3, C3bc/C3, C4, C4bc/C4, C5a, and Membrane Attack Complex in peripheral blood were analyzed and complement activation in the skin was determined by the analysis of C4d deposition. Results were related to the clinical response to omalizumab. Results Fifteen patients showed a UAS7 score of 6 or lower (median 0) at Week 24, 15 patients did not (median 16). Lesional skin biopsies at baseline revealed complement deposition (C4d) in blood vessels in the papillary dermis of 53% (16/30) of the patients, which suggests involvement of immune complexes in the pathogenesis of urticaria. Moreover, indication of increased complement activation in CSU was substantiated by increased C5a levels in peripheral blood compared to healthy controls (p = 0.010). The clinical effect of omalizumab could not be linked to the variation of complement components. Conclusions Both C4d deposition in lesional skin and elevated C5a levels in peripheral blood indicate the involvement of complement activation in the pathogenesis of CSU. No correlation was found between omalizumab and activation of complement indicative of independent processes in the immunopathogenesis of CSU.

Published
2021

20. EASI p‐EASI: Predicting disease severity in atopic dermatitis patients treated with dupilumab using a combination of serum biomarkers

Author

Julia Drylewicz, Eveline M. Delemarre, Stefan Nierkens, Judith L. Thijs, Edward F. Knol, Lieneke F.M. Ariëns, DirkJan Hijnen, Marjolein S. de Bruin-Weller, Barbara Giovannone, Daphne S. Bakker, and Dermatology

Subjects
Biological Products, medicine.medical_specialty, atopic dermatitis, business.industry, Immunology, biomarkers, Antibodies, Monoclonal, Atopic dermatitis, Antibodies, Monoclonal, Humanized, medicine.disease, Severity of Illness Index, Dermatology, Dupilumab, Dermatitis, Atopic, Treatment Outcome, Disease severity, Serum biomarkers, medicine, Humans, Immunology and Allergy, biologics, Dermatologic Agents, Letters to the Editor, business, Letter to the Editor
Published
2020

21. Measurement of IgE to hazelnut allergen components cannot replace hazelnut challenge in Dutch adults

Author

Paco M J Welsing, Thuy-My Le, Mariam Hakobyan, Hannah M. Kansen, Henny G. Otten, André C. Knulst, Sarah A. Lyons, Edward F. Knol, Ronald van Ree, Ear, Nose and Throat, Experimental Immunology, AII - Inflammatory diseases, APH - Global Health, and APH - Personalized Medicine

Subjects
Immunology, Diagnostic accuracy, medicine.disease_cause, Immunoglobulin E, Serum ige, component-resolved diagnostics, Allergen, Corylus, adults, Immunology and Allergy, Medicine, Humans, hazelnut allergy, biology, business.industry, Plant Extracts, Area under the curve, Allergens, Antigens, Plant, Hazelnut allergy, Dutch Population, biology.protein, IgE, diagnostic value, Nut Hypersensitivity, business, Challenge testing
Abstract

Background Component-resolved diagnostics (CRD) help predict hazelnut allergy (HA) in children, but are of unknown diagnostic value in adults. This study aimed to evaluate the diagnostic accuracy of IgE to hazelnut extract and components in adults. Methods A Dutch population of consecutively presenting adults suspected of HA, who underwent a double-blind placebo-controlled food challenge, were included. Serum IgE to hazelnut extract and Cor a 1, 8, 9 and 14 was measured on ImmunoCAP. Diagnostic accuracy was assessed by area under the curve (AUC) analysis. Results Of 89 patients undergoing challenge, 46 had challenge-confirmed HA: 17 based on objective and 29 based on subjective symptoms. At commonly applied cutoffs 0.1 and 0.35 kUA /L, high sensitivity was observed for IgE to hazelnut extract and Cor a 1 (range 85-91%), and high specificity for IgE to Cor a 8, 9 and 14 (range 77-95%). However, the AUCs for hazelnut extract and components were too low for accurate prediction of HA (range 0.50-0.56). Combining hazelnut extract and component IgE measurements did not significantly improve accuracy. Higher IgE levels to Cor a 9 and 14 were tentatively associated with HA with objective symptoms, but the corresponding AUCs still only reached 0.68 and 0.63 respectively. Conclusions Although hazelnut allergic adults are generally sensitized to hazelnut extract and Cor a 1, and hazelnut tolerant adults are usually not sensitized to Cor a 8, 9 or 14, challenge testing is still needed to accurately discriminate between presence and absence of HA in adults from a birch-endemic country.

Published
2021

22. Immune modulation via T regulatory cell enhancement: disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases - An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)

Author

Antonios G.A. Kolios, Ian M. Adcock, Betty C.A.M. van Esch, Onur Boyman, Zuzana Diamant, Cristina Benito-Villalvilla, Francesca Levi-Schaffer, Frank A. Redegeld, Giuseppe Nocentini, Kian Fan Chung, Leif Bjermer, Luigi Cari, Rodolfo Bianchini, Gaetano Caramori, Ibon Eguiluz-Gracia, Oscar Palomares, Cristiana Stellato, Edward F. Knol, Franziska Roth-Walter, Afd Pharmacology, Pharmacology, University of Zurich, and Stellato, Cristiana

Subjects
Adoptive cell transfer, Disease, medicine.disease_cause, T-Lymphocytes, Regulatory, FOOD ALLERGY, adoptive cell therapies, Autoimmunity, CONFERS PROTECTION, 0302 clinical medicine, allergy, autoimmunity, CAR-Treg cells, immunoregulation, Immunology and Allergy, LYMPHOCYTE-ACTIVATION, EXPERIMENTAL COLITIS, 10177 Dermatology Clinic, MOUSE MODEL, CAR&#8208, medicine.anatomical_structure, 1107 Immunology, 2723 Immunology and Allergy, Allergen immunotherapy, T cell, Immunology, DNA METHYLTRANSFERASE, 610 Medicine & health, Autoimmune Diseases, 03 medical and health sciences, Immune system, medicine, Hypersensitivity, Humans, ADOPTIVE TRANSFER, 2403 Immunology, TRANSCRIPTION FACTOR FOXP3, business.industry, Immunopharmacology, Asthma, Transplantation, ATTENUATES AIRWAY INFLAMMATION, ORAL TOLERANCE, 030228 respiratory system, 10033 Clinic for Immunology, business, Treg cells, 030215 immunology
Abstract

Therapeutic advances using targeted biologicals and small-molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune, and inflammatory diseases particularly for some patients with severe, treatment-resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements, not all severe forms of chronic inflammatory and autoimmune diseases are successfully targeted, and current treatment options, besides allergen immunotherapy for selected allergic diseases, fail to change the disease course. T cell-based therapies aim to cure diseases through the selective induction of appropriate immune responses following the delivery of engineered, specific cytotoxic, or regulatory T cells (Tregs). Adoptive cell therapies (ACT) with genetically engineered T cells have revolutionized the oncology field, bringing curative treatment for leukemia and lymphoma, while therapies exploiting the suppressive functions of Tregs have been developed in nononcological settings, such as in transplantation and autoimmune diseases. ACT with Tregs are also being considered in nononcological settings such as cardiovascular disease, obesity, and chronic inflammatory disorders. After describing the general features of T cell-based approaches and current applications in autoimmune diseases, this position paper reviews the experimental models testing or supporting T cell-based approaches, especially Treg-based approaches, in severe IgE-mediated responses and chronic respiratory airway diseases, such as severe asthma and COPD. Along with an assessment of challenges and unmet needs facing the application of ACT in these settings, this article underscores the potential of ACT to offer curative options for patients with severe or treatment-resistant forms of these immune-driven disorders.

Published
2021

23. COVID‐19 pandemic and allergen immunotherapy—an EAACI survey

Author

Isabel J. Skypala, Ludger Klimek, Montserrat Alvaro-Lozano, Oliver Pfaar, Ioana Agache, Helen A. Brough, Oscar Palomares, Adam Chaker, Eva Untersmayr, Jürgen Schwarze, Karin Hoffmann-Sommergruber, Erika Jensen-Jarolim, Mattia Giovannini, Marek Jutel, Charlotte G. Mortz, Cristina Quecchia, Aslı Gelincik, Antti Lauerma, Jolanta Walusiak-Skorupa, Vesna Tomic Spiric, Umit Murat Sahiner, María José Torres, Mónica Sandoval-Ruballos, Edward F. Knol, Tomas Chivato, Matteo Bonini, Liam O'Mahony, Radosław Gawlik, Carmen Riggioni, Stefano Del Giacco, Markus Ollert, Enrico Heffler, HUS Inflammation Center, and Department of Dermatology, Allergology and Venereology

Subjects
Intoxicative inhalant, Pediatrics, Allergy, IMPACT, SARS‐CoV‐2, 0302 clinical medicine, Surveys and Questionnaires, Pandemic, Original Article: Allergen‐specific Immunotherapy and Biologics, Immunology and Allergy, 0303 health sciences, allergen immunotherapy (AIT), SARS-CoV-2, 3. Good health, ddc, Tolerability, pandemic, COVID-19, safety, Allergen immunotherapy, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, 03 medical and health sciences, Original Articles: Allergen‐specific Immunotherapy and Biologics, COVID‐19, medicine, Humans, survey, TELEMEDICINE, practicability, Pandemics, 030304 developmental biology, Asthma, Retrospective Studies, business.industry, SERVICES, medicine.disease, RHINOCONJUNCTIVITIS, 030228 respiratory system, Desensitization, Immunologic, 3121 General medicine, internal medicine and other clinical medicine, ASTHMA, business
Abstract

Background: As in many fields of medical care, the coronavirus disease 2019 (COVID-19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and systematically collect all information available regarding tolerability and possible amendments in daily practice of sublingual AIT (SLIT), subcutaneous AIT (SCIT) for inhalant allergies and venom AIT.Method: Under the framework of the EAACI, a panel of experts in the field of AIT coordinated by the Immunotherapy Interest Group (IT IG) set-up a web-based retrospective survey (SurveyMonkey®) including 27 standardized questions on practical and safety aspects on AIT in worldwide clinical routine. Results: 417 respondents providing AIT to their patients in daily routine answered the survey. For patients (without any current symptoms to suspect COVID-19), 60% of the respondents informed of not having initiated SCIT (40% venom AIT, 35% SLIT) whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID-19 and/or a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Conclusions: This first international retrospective survey in atopic diseases investigated practical aspects and tolerability of AIT during the COVID-19 pandemic and gave no concerns regarding reduced tolerability under real-life circumstances. However, the data indicate an undertreatment of AIT, which may be temporary, but could have a long-lasting negative impact on the clinical care of allergic patients. Keywords: COVID-19, allergen immunotherapy (AIT), SARS-CoV-2, practicability, survey, safety, pandemic

Published
2020

24. Immunology of COVID‐19: mechanisms, clinical outcome, diagnostics and perspectives – a report of the European Academy of Allergy and Clinical Immunology (EAACI)

Author

Wojciech Feleszko, Isabella Pali-Schöll, Weronika Barcik, Jozef Janda, Hideaki Morita, Rodrigo Jiménez-Saiz, Gerdien A. Tramper-Stranders, Willem van de Veen, Kari C. Nadeau, Marcin Moniuszko, Akash Kothari, Oscar Palomares, Cezmi A. Akdis, Cristina Gomez-Casado, Karin Hoffmann-Sommergruber, Stefanie Eyerich, Inge Kortekaas Krohn, Joanna Makowska, Mohamed H. Shamji, Carsten B. Schmidt-Weber, Anna Sediva, Helen A. Brough, Mary Prunicki, Zuzanna Lukasik, Eva Untersmayr, Francesco Papaleo, Milena Sokolowska, Mübeccel Akdis, Ioana Agache, Cevdet Ozdemir, Andrzej Eljaszewicz, Thomas Eiwegger, Edward F. Knol, Deniz Akdis, Marek Jutel, Jürgen Schwarze, Liam O'Mahony, European Academy of Allergy and Clinical Immunology, Swiss National Science Foundation, Ministerio de Economía y Competitividad (España), Research Foundation - Flanders, Istituto Italiano di Tecnologia, Fondazione Telethon, Ministero della Salute, Comunidad de Madrid, German Research Foundation, European Commission, Sokolowska, Milena, Agache, Ioana, Akdis, Cezmi A., Akdis, Mubeccel, Barcik, Weronika, Brough, Helen, Eiwegger, Thomas, Eliaszewicz, Andrzej, Feleszko, Wojciech, Gómez-Casado, C., Hoffmann-Sommergruber, Karin, Janda, Jozef, Jiménez Saiz, Rodrigo, Knol, Edward, Krohn, Kortekaas, Kothari, Akash, Moniuszko, Marcin, Morita, Hideaki, Nadeau, Kari C., Ozdemir, Cevdet, Pali-Schöll, Isabella, Palomares, O., Papaleo, Francesco, Prunicki, Mary, Schmidt-Weber, C. B., Schwarze, Jürgen, Tramper-Stranders, Gerdien, Veen, Willem van de, Untersmayr, Eva, Dermatology, Sokolowska, Milena [0000-0001-9710-6685], Agache, Ioana [0000-0001-7994-364X], Akdis, Cezmi A. [0000-0001-8020-019X], Akdis, Mubeccel [0000-0003-0554-9943], Barcik, Weronika [0000-0001-8580-9690], Brough, Helen [0000-0001-7203-0813], Eiwegger, Thomas [0000-0002-2914-7829], Eliaszewicz, Andrzej [0000-0002-8980-1474], Feleszko, Wojciech [0000-0001-6613-2012], Gómez-Casado, C. [0000-0002-7707-6367], Hoffmann-Sommergruber, Karin [0000-0002-8830-058X], Janda, Jozef [0000-0001-9958-5683], Jiménez Saiz, Rodrigo [0000-0002-0606-3251], Knol, Edward [0000-0001-7368-9820], Krohn, Kortekaas [0000-0003-3649-1131], Kothari, Akash [0000-0003-1980-161X], Moniuszko, Marcin [0000-0001-7183-3120], Morita, Hideaki [0000-0003-0928-8322], Nadeau, Kari C. [0000-0002-2146-2955], Ozdemir, Cevdet [0000-0002-9284-4520], Pali-Schöll, Isabella [0000-0003-2089-6011], Palomares, O. [0000-0003-4516-0369], Papaleo, Francesco [0000-0002-6326-0657], Prunicki, Mary [0000-0002-5511-8896], Schmidt-Weber, C. B. [0000-0002-3203-8084], Schwarze, Jürgen [0000-0002-6899-748X], Tramper-Stranders, Gerdien [0000-0002-0228-5375], Veen, Willem van de [0000-0001-9951-6688], and Untersmayr, Eva [0000-0002-1963-499X]

Subjects
medicine.medical_specialty, Allergy, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Pneumonia, Viral, Eaaci Position Paper, SARS‐CoV‐2 receptors, Disease, medicine.disease_cause, COVID‐19 treatment, 03 medical and health sciences, Betacoronavirus, COVID‐19 prevention, 0302 clinical medicine, Immune system, COVID-19 Testing, Pandemic, medicine, Immunology and Allergy, Humans, Intensive care medicine, Pandemics, Coronavirus, SARS, business.industry, Clinical Laboratory Techniques, SARS-CoV-2, Academies and Institutes, COVID‐19 comorbidity, COVID-19, biochemical phenomena, metabolism, and nutrition, Acquired immune system, medicine.disease, 3. Good health, 030228 respiratory system, COVID‐19 immunity, COVID‐19 multi‐morbidity, business, Coronavirus Infections, 030215 immunology
Abstract

With the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS‐CoV‐2‐induced Coronavirus disease‐19 (COVID‐19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS‐CoV‐2 infection and COVID‐19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multi‐organ disease. The similarities of the human immune response to SARS‐CoV‐2 and the SARS‐CoV and MERS‐CoV are underlined. We also summarize known and potential SARS‐CoV‐2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender and age in development of COVID‐19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID‐19 studies., The authors would like to thank the European Academy of Allergy and Clinical Immunology (EAACI) for the financial support to the sections, interest groups and working groups enabling the development of this paper. The research of SM is supported by a SNSF grant 310039_189334; JSR is funded by Ministerio de Economía y Competitividad (IJCI-2016-27619); KKI is supported by the FWO Post doc mandate 12W2219N; BW and PF were supported by funding from the Istituto Italiano di Tecnologia, Fondazione Telethon (project GGP19103), and Ricerca Finalizzata Giovani Ricercatori 2016 - Ministero Salute Italia (project GR-2016-02362413); GCC is supported by a postdoctoral contract cofounded by the competitive Program “Attracting Talent,” Community of Madrid, Spain; the research of SWCB was funded by DFG (398577603), “ADAPT” EIT Health is a body of the EU receiving support from H2020 and BMBF “ESCAPE” 01KI20169A; the research of UE is supported by the H2020 grant 768641 and by the BMF grant 19056.

Published
2020

25. Accurate Prediction of Peanut Allergy in One-Third of Adults Using a Validated Ara h 2 Cutoff

Author

Cornelis K. van der Ent, Yolanda Meijer, Anna M. Ehlers, Henny G. Otten, Francine C. van Erp, Thuy-My Le, Sarah A. Lyons, André C. Knulst, Hannah M. Kansen, and Edward F. Knol

Subjects
Adult, medicine.medical_specialty, Arachis, Peanut allergy, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Daily practice, Immunology and Allergy, Medicine, Cutoff, Humans, Peanut Hypersensitivity, 030212 general & internal medicine, Child, Glycoproteins, Receiver operating characteristic, business.industry, Area under the curve, food and beverages, Allergens, Antigens, Plant, Immunoglobulin E, medicine.disease, Predictive value, Confidence interval, 030228 respiratory system, business, 2S Albumins, Plant
Abstract

Background The diagnostic value of peanut components is extensively studied in children, but to a lesser extent in adults with suspected peanut allergy. The use of peanut components in daily practice may reduce the need for double-blind placebo-controlled food challenges (DBPCFCs); however, validation studies are currently lacking. Objective To evaluate the diagnostic value of (combined) peanut components and validate a previously found Ara h 2 cutoff level with 100% positive predictive value (PPV) in adults with suspected peanut allergy. Methods Adults who underwent a peanut DBPCFC were included: 84 patients from a previous study (2002-2012) and 70 new patients (2012-2019). Specific IgE (sIgE) to peanut extract, Ara h 1, 2, 3, 6, and 8 was measured using ImmunoCAP. Diagnostic value was assessed with an area under the curve (AUC) analysis. Results In total, 95 (62%) patients were peanut allergic. sIgE to Ara h 2 and Ara h 6 were the best predictors with an AUC (95% confidence interval) of 0.85 (0.79-0.91) and 0.85 (0.79-0.92), respectively. The Ara h 2 cutoff level with 100% PPV (≥1.75 kUA/L) was validated in the 70 new patients. Thirty percent of all included patients could be classified correctly as peanut allergic using this validated cutoff level. Conclusion sIgE to Ara h 2 and Ara h 6 have equally high discriminative ability. Peanut allergy can be predicted accurately in one-third of adults using a validated cutoff level of sIgE to Ara h 2.

Published
2020

26. ARIA���EAACI statement on asthma and COVID���19 (June 2, 2020)

Author

Tari Haahtela, Victoria Cardona, Alvaro A. Cruz, Anna Bedbrook, Ken Ohta, Wienczyslawa Czarlewski, Nikos G. Papadopoulos, Marc Humbert, Menachem Rottem, Violeta Kvedariene, Omar S. Usmani, Eric D. Bateman, Helga Kraxner, Ludger Klimek, Hubert Blain, Thomas B. Casale, Mário Morais-Almeida, Aziz Sheikh, Joaquin Sastre, Piotr Kuna, Giovanni Rolla, Nataliya Ilina, Thomas Eiwegger, Seppo Koskinen, Tomas Chivato, Torsten Zuberbier, Nicola Scichilone, De Yun Wang, Luisa Brussino, Désirée Larenas-Linnemann, Manuel Soto-Martínez, Maciej Kupczyk, Karin Hoffmann-Sommergruber, Sharon Chinthrajah, Karl Christian Bergmann, M. Gotua, Sinthia Bosnic-Anticevich, Charlotte Suppli-Ulrik, Marek L. Kowalski, Mübeccel Akdis, Bilun Gemicioglu, Petr Panzner, Giovanni Viegi, Elisabete Nunes, Jürgen Schwarze, Sanna Toppila-Salmi, Ioanna Tsiligianni, Hui Du, Wytske Fokkens, Maria Teresa Ventura, Eckard Hamelmann, Paulo Augusto Moreira Camargos, Dmitry Kudlay, Mateo Bonini, Sian Williams, Mina Gaga, Louis-Philippe Boulet, Ignacio J. Ansotegui, Teresa To, Oliver Pfaar, Ioana Agache, Giorgio Walter Canonica, João Fonseca, Leyla Namazova, K. S. Bennoor, Elena Camelia Berghea, Ya-dong Gao, Roland Buhl, David M.G. Halpin, Gabrielle L. Onorato, Nhân Pham-Thi, Todor A. Popov, Mihaela Zidarn, Stefania Nicola, Branislava Milenkovic, Robyn E O'Hehir, Kari C. Nadeau, Juan Carlos Ivancevich, Luís Taborda-Barata, Florin Mihaltan, Amir Hamzah Abdul Latiff, Rafael Stelmach, Marek Jutel, Frederico S. Regateiro, B. Pigearias, Theodor Vontetsianos, Ruby Pawankar, Mohammad R. Masjedi, Renaud Louis, Musa Khaitov, Manuel E. Soto-Quiros, Lan T. Le, H. Neffen, Yousser Mohammad, Yoshitaka Okamoto, Fanny W.S. Ko, Yehia El-Gamal, Edward F. Knol, Gary W.K. Wong, Guy Joos, Gianni Passalacqua, Jean Bousquet, Paul M. O'Byrne, Arunas Valiulis, Cezmi A. Akdis, George Christoff, Bolesław Samoliński, Claus Bachert, Vincenzo Patella, Josep M. Antó, Arzu Yorgancioglu, Michael Levin, Liam O'Mahony, Mario E. Zernotti, Erik Melén, Joaquim Mullol, Peter Valentin Tomazic, Stefano Del Giacco, Francesca Puggioni, Milan Sova, Bruce Kirenga, UAM. Departamento de Medicina, Ear, Nose and Throat, AII - Inflammatory diseases, Bousquet J., Jutel M., Akdis C.A., Klimek L., Pfaar O., Nadeau K.C., Eiwegger T., Bedbrook A., Ansotegui I.J., Anto J.M., Bachert C., Bateman E.D., Bennoor K.S., Berghea E.C., Bergmann K.-C., Blain H., Bonini M., Bosnic-Anticevich S., Boulet L.-P., Brussino L., Buhl R., Camargos P., Canonica G.W., Cardona V., Casale T., Chinthrajah S., Akdis M., Chivato T., Christoff G., Cruz A.A., Czarlewski W., Del Giacco S., Du H., El-Gamal Y., Fokkens W.J., Fonseca J.A., Gao Y., Gaga M., Gemicioglu B., Gotua M., Haahtela T., Halpin D., Hamelmann E., Hoffmann-Sommergruber K., Humbert M., Ilina N., Ivancevich J.-C., Joos G., Khaitov M., Kirenga B., Knol E.F., Ko F.W., Koskinen S., Kowalski M.L., Kraxner H., Kudlay D., Kuna P., Kupczyk M., Kvedariene V., Abdul Latiff A.H., Le L.T., Levin M., Larenas-Linnemann D., Louis R., Masjedi M.R., Melen E., Mihaltan F., Milenkovic B., Mohammad Y., Morais-Almeida M., Mullol J., Namazova L., Neffen H., Nunes E., O'Byrne P., O'Hehir R., O'Mahony L., Ohta K., Okamoto Y., Onorato G.L., Panzner P., Papadopoulos N.G., Passalacqua G., Patella V., Pawankar R., Pham-Thi N., Pigearias B., Popov T.A., Puggioni F., Regateiro F.S., Rolla G., Rottem M., Samolinski B., Sastre J., Schwarze J., Sheikh A., Scichilone N., Soto-Quiros M., Soto-Martinez M., Sova M., Nicola S., Stelmach R., Suppli-Ulrik C., Taborda-Barata L., To T., Tomazic P.-V., Toppila-Salmi S., Tsiligianni I., Usmani O., Valiulis A., Ventura M.T., Viegi G., Vontetsianos T., Wang D.Y., Williams S., Wong G.W.K., Yorgancioglu A., Zernotti M., Zidarn M., Zuberbier T., and Agache I.

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Allergy, Statement (logic), Medicina, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, Immunology, Settore MED/10 - Malattie Dell'Apparato Respiratorio, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, astma, Medicine and Health Sciences, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Letters to the Editor, Letter to the Editor, udc:616.2, Asthma, Coronavirus, Science & Technology, business.industry, SARS-CoV-2, virus diseases, COVID-19, asthma, medicine.disease, Virology, 3. Good health, 030228 respiratory system, covid-19, 1107 Immunology, Angiotensin-Converting Enzyme 2, business, ARIA-EAACI, Life Sciences & Biomedicine, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Abstract

Artículo con numerosos autores sólo se mencionan el primero y el de la UAM, Open access funding enabled and organized by Projekt DEAL

Published
2020
Full Text
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27. A field-applicable method for flow cytometric analysis of granulocyte activation

Author

Nienke Vrisekoop, Leo Koenderman, Bart Hilvering, Karin de Ruiter, Edward F. Knol, Maria Yazdanbakhsh, Selma van Staveren, and Pulmonary medicine

Subjects
0301 basic medicine, Granulocyte activation, Histology, cryopreservation, Cryopreservation, Pathology and Forensic Medicine, Flow cytometry, 03 medical and health sciences, activation marker, medicine, Humans, medicine.diagnostic_test, biology, Cell adhesion molecule, Chemistry, flow cytometry, Granule (cell biology), Cell Biology, granulocytes, Molecular biology, Staining, 030104 developmental biology, field study, Integrin alpha M, biology.protein, Cytometry
Abstract

Upon activation granulocytes upregulate several adhesion molecules (CD11b) and granule proteins (CD35, CD66b) and shed surface l-selectin (CD62L). These changes in expression, as assessed by flow cytometry, can be used as markers for activation. Whereas these markers are usually studied in fresh blood samples, a new method is required when samples are collected at a field site with no direct access to a flow cytometer. Therefore, we developed and tested a field-applicable method in which fixed leukocytes were cryopreserved. Using this method, the intensity of granulocyte activation markers was compared to samples that were either stained fresh, or fixed prior to staining but not cryopreserved. In addition, the response to an in vitro stimulation with fMLF was determined. While we observed differences in marker intensities when comparing fresh and fixed granulocytes, similar intensities were found between fixed cells that had been cryopreserved and fixed cells that did not undergo cryopreservation. Although fixation using FACS lysing solution might lead to membrane permeabilization, activation markers, and the responsiveness to fMLF or eotaxin could still be clearly measured. This method will, therefore, enable future studies of granulocyte activation in settings with limited resources and will allow simultaneous analysis of samples collected at different time points. © 2018 International Society for Advancement of Cytometry.

Published
2018

28. EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy

Author

Ulugbek Nurmatov, Aziz Sheikh, Kari C. Nadeau, Edward F. Knol, Mika J. Mäkelä, Carsten Bindslev-Jensen, R. G. Van Wijk, Ioana Agache, M. Ebisawa, Oliver Pfaar, E-M. Varga, S. Dhami, Cezmi A. Akdis, Philippe Eigenmann, Y Boloh, Cansin Sackesen, Nikolaos G. Papadopoulos, Montserrat Alvaro-Lozano, G. Du Toit, Graham Roberts, Antonella Muraro, Montserrat Fernandez-Rivas, Elizabeth Angier, Kirsten Beyer, Stefania Arasi, Dermot Ryan, Steffen Lau, Marek Jutel, Liam O'Mahony, R. van Ree, Susanne Halken, Gunter J. Sturm, Alexandra F. Santos, Giovanni B. Pajno, Lars K. Poulsen, Wesley Burks, APH - Personalized Medicine, AII - Inflammatory diseases, APH - Global Health, Experimental Immunology, Ear, Nose and Throat, and Internal Medicine

Subjects
Allergy, medicine.medical_treatment, Desensitization, medicine.disease_cause, 0302 clinical medicine, Allergen, allergy, Medicine, Immunology and Allergy, 030212 general & internal medicine, allergen immunotherapy, Desensitization (medicine), Allergen immunotherapy, Pediatric, Food Hypersensitivity/prevention & control, ddc:618, adult, pediatric, 3. Good health, Tolerance induction, Immunoglobulin E/immunology, Immunologic/methods/standards, adolescent, Food Hypersensitivity, Adult, medicine.medical_specialty, Adolescent, Immunology, 03 medical and health sciences, Food allergy, Internal medicine, Animals, Humans, Eosinophilic esophagitis, business.industry, food, Immunoglobulin E, medicine.disease, Adolescent, Adult, Allergen immunotherapy, Allergy, Food, Pediatric, Immunology and Allergy, Immunology, 030228 respiratory system, Desensitization, Immunologic, Food, Egg allergy, business
Abstract

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

Published
2018

30. Seeking diagnostic and prognostic biomarkers for childhood bacterial pneumonia in sub-Saharan Africa: study protocol for an observational study

Author

Julio Ramirez, Grant A. Mackenzie, Alejandro A. Diaz, Edward F. Knol, Roger C. Wiegand, Wilco de Jager, Quique Bassat, Sheriffo Kanyi, Sarwar Golam, Yasir Shitu Isa, Rasheed Salaudeen, Abdoulie Jammeh, Clarissa Valim, Yekin Ajauoi Olatunji, Marsha A. Moses, Umberto D'Alessandro, and Patricia L. Hibberd

Subjects
medicine.medical_specialty, Disease, paediatric infectious disease & immunisation, respiratory infections, Pneumonia, Bacterial, Humans, Medicine, Child, Intensive care medicine, Diagnostics, Africa South of the Sahara, Bacterial disease, business.industry, Bacterial pneumonia, General Medicine, Prognosis, diagnostic microbiology, medicine.disease, Institutional review board, Anti-Bacterial Agents, Observational Studies as Topic, Pneumonia, paediatric thoracic medicine, Etiology, Observational study, business, Biomarkers, Malaria
Abstract

IntroductionClinically diagnosed pneumonia in children is a leading cause of paediatric hospitalisation and mortality. The aetiology is usually bacterial or viral, but malaria can cause a syndrome indistinguishable from clinical pneumonia. There is no method with high sensitivity to detect a bacterial infection in these patients and, as result, antibiotics are frequently overprescribed. Conversely, unrecognised concomitant bacterial infection in patients with malarial infections occur with omission of antibiotic therapy from patients with bacterial infections. Previously, we identified two combinations of blood proteins with 96% sensitivity and 86% specificity for detecting bacterial disease. The current project aimed to validate and improve these combinations by evaluating additional biomarkers in paediatric patients with clinical pneumonia. Our goal was to describe combinations of a limited number of proteins with high sensitivity and specificity for bacterial infection to be incorporated in future point-of-care tests. Furthermore, we seek to explore signatures to prognosticate clinical pneumonia.Methods and analysisPatients (n=900) aged 2–59 months presenting with clinical pneumonia at two Gambian hospitals will be enrolled and classified according to criteria for definitive bacterial aetiology (based on microbiological tests and chest radiographs). We will measure proteins at admission using Luminex-based immunoassays in 90 children with definitive and 160 with probable bacterial aetiology, and 160 children classified according to the prognosis of their disease. Previously identified diagnostic signatures will be assessed through accuracy measures. Moreover, we will seek new diagnostic and prognostic signatures through machine learning methods, including support vector machine, penalised regression and classification trees.Ethics and disseminationEthics approval has been obtained from the Gambia Government/Medical Research Council Unit The Gambia Joint Ethics Committee (protocol 1616) and the institutional review board of Boston University Medical Centre (STUDY00000958). Study results will be disseminated to the staff of the study hospitals, in scientific seminars and meetings, and in publications.Trial registration numberH-38462.

Published
2021

31. Management of Cow's Milk Allergy from an Immunological Perspective : What Are the Options?

Author

Nicolette W. de Jong, Edward F. Knol, Laurien H. Ulfman, Machteld M. Tiemessen, and Internal Medicine

Subjects
0301 basic medicine, Adult, Allergy, Milk allergy, lcsh:TX341-641, Immunoglobulin E, Epitope, 03 medical and health sciences, 0302 clinical medicine, Immune system, Cow's milk allergy, Allergic symptoms, medicine, Animals, Humans, Child, Cow’s milk, Nutrition and Dietetics, biology, business.industry, Communication, Immune cells, Infant, medicine.disease, Infant Formula, 030104 developmental biology, 030228 respiratory system, Immunology, biology.protein, Formula, Immunoglubuline E, Cattle, Therapy, Milk Hypersensitivity, business, lcsh:Nutrition. Foods and food supply, Allergic process, Food Science
Abstract

The immunological mechanism underlying Immunoglobuline E (IgE)-mediated cow’s milk allergy has been subject to investigations for many years. Identification of the key immune cells (mast cells, B cells) and molecules (IgE) in the allergic process has led to the understanding that avoidance of IgE-crosslinking epitopes is effective in the reduction of allergic symptoms but it cannot be envisioned as a treatment. For the treatment and prevention of IgE-mediated cow’s milk allergy, it is thought that the induction of a sustained state of immunological tolerance is needed. In this review, we will discuss various approaches aimed at achieving immunological tolerance and their success. Furthermore, we will speculate on the involved immunological mechanism.

Published
2019

32. EAACI Research and Outreach Committee: Improving standards and facilitating global collaboration through a Research Excellence Network

Author

Mohamed H. Shamji, Oscar Palomares, Stefano Del Giacco, Ioana Agache, Sylwia Smolinska, Liam O'Mahony, Domingo Barber, Marek Jutel, Karin Hoffman-Sommergruber, Markus Ollert, Jürgen Schwarze, Cezmi A. Akdis, Tomas Chivato, Edward F. Knol, Stefan Vieths, Walter Canonica, and Joaquín Sastre

Subjects
food allergy, Medical education, Clinical immunology, business.industry, allergy treament, media_common.quotation_subject, Immunology, MEDLINE, biomarkers, Reference Standards, Outreach, allergy diagnosis, Excellence, Hypersensitivity, Immunology and Allergy, Medicine, Humans, business, clinical immunology, media_common
Published
2019

33. Response of FcεRI-bearing leucocytes to omalizumab in chronic spontaneous urticaria

Author

Heike Röckmann, Henny G. Otten, Mignon T. van den Elzen, Constance F. den Hartog Jager, André C. Knulst, Harmieke van Os-Medendorp, Mehran Alizadeh Aghdam, and Edward F. Knol

Subjects
0301 basic medicine, Adult, Male, skin, FcεRI, Immunology, Basic Mechanisms in Allergic Disease, chemical and pharmacologic phenomena, Omalizumab, Basophil, high‐affinity IgE receptor, Basophil degranulation, Pathogenesis, 03 medical and health sciences, urticaria, 0302 clinical medicine, parasitic diseases, medicine, Leukocytes, Immunology and Allergy, Humans, Clinical significance, Chronic Urticaria, Prospective Studies, Prospective cohort study, Aged, business.industry, Receptors, IgE, basophil degranulation, therapy response, Degranulation, hemic and immune systems, Dendritic cell, Middle Aged, 030104 developmental biology, medicine.anatomical_structure, 030228 respiratory system, Female, Original Article, ORIGINAL ARTICLES, business, medicine.drug
Abstract

Background The pathogenesis of chronic spontaneous urticaria (CSU) and the mechanism of action of omalizumab in CSU remain unclear. Objective In this study, we assessed the responsiveness and FceRI expression of various subsets of leucocytes in patients with CSU treated with omalizumab. Methods In this prospective cohort study, 30 patients were treated with 6 administrations of 300 mg omalizumab every 4 weeks, followed by a follow-up period of 12 weeks. FceRI expression and the percentage of basophils, monocytes, and dendritic cell subsets were analysed before and during treatment, and after follow-up. In addition, anti-IgE- and C5a-induced basophil degranulation was measured. The results were correlated with disease activity and response to omalizumab. Results In addition to a rapid and significant reduction in FceRI on basophils, we demonstrated a reduction in FceRI on plasmacytoid dendritic cells during omalizumab treatment, which persisted until 3 months after discontinuation. FceRI expression on basophils and its reduction did not correlate with the treatment response. Omalizumab led to an increased percentage of basophils in blood but not of the other FceRI-bearing leucocytes. Basophil responsiveness was differentially affected; anti-IgE-, but not C5a-induced basophil degranulation increased during the treatment. Apart from clinical non-responders showing a stronger increase in anti-IgE-induced basophil degranulation over a period time, no differences were found in omalizumab responders vs non-responders. Conclusions/clinical relevance FceRI expression on basophils decreased rapidly, while anti-IgE-induced degranulation significantly increased due to omalizumab treatment in patients with CSU, persisting at least for 3 months after stopping the treatment. None of the markers were able to predict the effectiveness of treatment. Whether basophils play a role in omalizumab responsiveness in CSU remains unclear.

Published
2019

34. Early identification of atopic dermatitis patients in need of systemic immunosuppressive treatment

Author

Edward F. Knol, Jorien van der Schaft, Stefan Nierkens, Judith L. Thijs, Julia Drylewicz, Deepak M.W. Balak, Marjolein S. de Bruin-Weller, Eveline M. Delemarre, Barbara Giovannone, and Daphne S. Bakker

Subjects
Immunosuppressive treatment, Adult, Male, business.industry, Administration, Topical, Immunology, Atopic dermatitis, Middle Aged, medicine.disease, Research Letters, Dermatitis, Atopic, Adrenal Cortex Hormones, medicine, Research Letter, Immunology and Allergy, Humans, Identification (biology), Female, business, Biomarkers, Immunosuppressive Agents, Retrospective Studies
Published
2019

35. Pegvaliase: Immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy

Author

Edward F. Knol, Mohamed R. Daha, Ingo Müller, Nicola Longo, Knut Brockow, Oliver Hausmann, and Hope Northrup

Subjects
0301 basic medicine, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, Phenylalanine, Complement, Type III hypersensitivity, Review, 030105 genetics & heredity, Immune complex formation, Biochemistry, Antibodies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Maintenance therapy, Phenylketonurias, medicine, Genetics, Journal Article, Hypersensitivity, Phenylketonuria, Humans, Enzyme Replacement Therapy, Dosing, Intensive care medicine, Adverse effect, Molecular Biology, Phenylalanine Ammonia-Lyase, Immune complex, business.industry, Disease Management, Recombinant Proteins, ddc, Clinical trial, Hypersensitivity reaction, Diabetes and Metabolism, Phenylalanine ammonia lyase, Pegvaliase, Tolerability, Clinical Trials, Phase III as Topic, Premedication, business, 030217 neurology & neurosurgery
Abstract

Objective To provide recommendations for managing hypersensitivity adverse events (HAEs) to an injectable enzyme substitution therapy (pegvaliase, a PEGylated phenylalanine ammonia lyase enzyme) in adult patients with phenylketonuria (PKU). Methods Eight European academic immunology experts with a broad range of experience in hypersensitivity, anaphylaxis, and/or drug reactions, and two geneticists from the USA with pegvaliase experience convened for two advisory board meetings. Efficacy, safety, and immunological profile of pegvaliase were discussed with the objective of developing recommendations for the clinical management of HAEs associated with pegvaliase treatment. Results Based on available immunogenicity data, it was concluded that pegvaliase induces a Type III hypersensitivity reaction, causing HAEs with peak event rates during induction/titration and a decline over time during maintenance therapy. The decline in HAEs with longer duration of therapy was considered to likely be driven by anti-drug antibody affinity maturation, reduced immune complex formation, and decreased complement activation over time. Immunology and PKU experts unanimously supported that the use of an induction, titration, and maintenance dosing regimen and implementation of several risk mitigation strategies contributed to the improvement of tolerability over time. Key risk mitigation strategies utilized in the Phase 3 clinical trials such as premedication with H1-receptor antagonists, allowance for a longer titration period after an HAE, patient education, and requirement to carry auto-injectable adrenaline (epinephrine) should be continued in clinical practice. A tool for administration of auto-injectable adrenaline in patients using pegvaliase was suggested. It was added that after the occurrence of a severe HAE a temporary dose reduction is more likely to improve tolerability than treatment interruption. Conclusions Overall, it was agreed that pegvaliase has a generally tolerable safety profile in adults with PKU. Importantly, the risk mitigation strategies utilized in the clinical trials were considered to support the continued use of key strategies for management in the commercial setting, such as a slow induction/titration dosing paradigm and premedication with H1-receptor antagonists. However, physicians and patients need to be aware of the risk of HAEs associated with pegvaliase; presence of a trained observer during early treatment may be beneficial in certain circumstances, and a requirement to carry auto-injectable adrenaline is recommended. Because pegvaliase offers the possibility to normalize diet, while maintaining blood phenylalanine within the recommended therapeutic range, safe use of this medication in the clinical setting is important. Ongoing monitoring of long-term clinical safety of patients on pegvaliase treatment in the commercial setting was recommended.

Published
2019

36. Comparing biologicals and small molecule drug therapies for chronic respiratory diseases: An EAACI Taskforce on Immunopharmacology position paper

Author

Cristiana Stellato, Leif Bjermer, Luigi Cari, Edward F. Knol, Francesca Levi-Schaffer, Frank A. Redegeld, Kian Fan Chung, Oscar Palomares, Ibon Eguiluz-Gracia, Zuzana Diamant, Ian M. Adcock, Franziska Roth-Walter, Cristina Benito-Villalvilla, Betty C.A.M. van Esch, Gaetano Caramori, Rodolfo Bianchini, Antonios G.A. Kolios, Pier Giorgio Puzzovio, Giuseppe Nocentini, University of Zurich, and Stellato, Cristiana

Subjects
0301 basic medicine, Allergy, Respiratory Tract Diseases, Pulmonary Disease, Chronic Obstructive, DOUBLE-BLIND, 0302 clinical medicine, Eosinophilic, Immunology and Allergy, antibodies, Molecular Targeted Therapy, Pharmaceutical sciences, Non-U.S. Gov't, media_common, COPD, Research Support, Non-U.S. Gov't, Disease Management, INHIBITOR, asthma, biologicals, chronic obstructive pulmonary disease, small molecule drugs, Phenotype, Treatment Outcome, 2723 Immunology and Allergy, Drug, medicine.medical_specialty, PROSTAGLANDIN D-2, media_common.quotation_subject, Immunology, INNATE LYMPHOID-CELLS, 610 Medicine & health, CRTH2 ANTAGONIST, Research Support, OBSTRUCTIVE PULMONARY-DISEASE, Diagnosis, Differential, 03 medical and health sciences, Journal Article, medicine, Humans, Intensive care medicine, Asthma, CLUSTER-ANALYSIS, 2403 Immunology, Biological Products, business.industry, medicine.disease, Immunopharmacology, 030104 developmental biology, 030228 respiratory system, ANTIBODY, Chronic Disease, 10033 Clinic for Immunology, Position paper, Antibodies, Asthma, Biologicals, Chronic Obstructive Pulmonary Disease, Small Molecule Drugs, Immunology and Allerg, Immunology, business, Biomarkers
Abstract

Chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), together with their comorbidities, bear a significant burden on public health. Increased appreciation of molecular networks underlying inflammatory airway disease needs to be translated into new therapies for distinct phenotypes not controlled by current treatment regimens. On the other hand, development of new safe and effective therapies for such respiratory diseases is an arduous and expensive process. Antibody-based (biological) therapies are successful in treating certain respiratory conditions not controlled by standard therapies such as severe allergic and refractory eosinophilic severe asthma, while in other inflammatory respiratory diseases, such as COPD, biologicals are having a more limited impact. Small molecule drug (SMD)-based therapies represent an active field in pharmaceutical research and development. SMDs expand biologicals' therapeutic targets by reaching the intracellular compartment by delivery as either an oral or topically based formulation, offering both convenience and lower costs. Aim of this review was to compare and contrast the distinct pharmacological properties and clinical applications of SMDs- and antibody-based treatment strategies, their limitations and challenges, in order to highlight how they should be integrated for their optimal utilization and to fill the critical gaps in current treatment for these chronic inflammatory respiratory diseases.

Published
2019

37. Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study

Author

Martin K. Church, Elias Toubi, Petra Staubach, Gordon Sussman, Riccardo Asero, Nadine Marrouche, Carsten Bindslev-Jensen, Clive Grattan, Arno Kromminga, Marcus Maurer, Marta Ferrer, Per Stahl Skov, Tamar Kinaciyan, André Ellrich, Ulrike Raap, Ana Giménez-Arnau, Nicole Schoepke, Alvaro Daschner, George N. Konstantinou, Peter Schmid-Grendelmeier, Thilo Jakob, Michael Makris, Edward F. Knol, and Ke Zhang

Subjects
0301 basic medicine, chronic spontaneous urticaria, Male, Basophil, IgG autoantibodies, Immunoglobulin E, Autoantigens, Histamine Release, chemistry.chemical_compound, 0302 clinical medicine, Iron-Binding Proteins, Immunology and Allergy, Chronic Urticaria, Receptor, Autologous serum skin test, biology, Degranulation, Middle Aged, Chronic spontaneous urticaria, Antibodies, Anti-Idiotypic, Basophils, medicine.anatomical_structure, Phenotype, autologous serum skin test, Female, Symptom Assessment, Histamine, Adult, Adolescent, Immunology, Iodide Peroxidase, Autoimmune Diseases, 03 medical and health sciences, Young Adult, autoimmune CSU, medicine, Journal Article, Humans, Aged, Autoantibodies, business.industry, Receptors, IgE, Autoantibody, Basophil activation, 030104 developmental biology, 030228 respiratory system, chemistry, Immunoglobulin G, Basophil activation assays, biology.protein, Autoimmune CSU, business, basophil activation assays, Biomarkers
Abstract

Background: Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU. Methods: This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyroperoxidase (IgG anti-TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). Results: Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti-FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P

Published
2019

38. Basophil activation testing in diagnosis and monitoring of allergic disease – an overview

Author

Oliver Hausmann, Paul Rouzaire, Tatjana Pecaric-Petkovic, Wayne G. Shreffler, Sarita U. Patil, Marta Ferrer, Hans Jürgen Hoffmann, Didier G. Ebo, Cristobalina Mayorga, Bernadette Eberlein, Anna Nopp, Edward F. Knol, Peter Korošec, Vito Sabato, Alexandra F. Santos, and Maria L. Sanz

Subjects
0301 basic medicine, Allergen immunotherapy, Allergy, Basophil activation test, Drug allergy, Basophil, Immunoglobulin E, medicine.disease_cause, Allergen provocation, 03 medical and health sciences, 0302 clinical medicine, Allergen, Allergy diagnosis, CD63, medicine, Immunology and Allergy, Basophil granulo, Cyte, biology, business.industry, Allergy monitoring, BAT, medicine.disease, Challenge testing, Basophil activation, 030104 developmental biology, medicine.anatomical_structure, 030228 respiratory system, Immunology, biology.protein, Human medicine, business
Abstract

The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. Through the development of flow cytometry, discovery of activation markers such as CD63 and markers identifying basophil granulocytes, the basophil activation test ( BAT) has become a pervasive test. BAT measures basophil response to allergen crosslinking IgE on between 150 and 2,000 basophil granulocytes with remarkable analytical sensitivity in < 0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In patients with food-, insect venom-, and drug allergy and patients with chronic urticaria BAT can be part of the diagnostic evaluation in addition to history, skin prick testing, and specific IgE determination. BAT may also be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment, or in the natural resolution of allergy. The test may use fewer resources and be more reproducible than oral, sting, nasal or bronchial challenge testing. BAT may be useful before challenge testing as it is less stressful for the patient and avoids severe allergic reactions. It may be useful before challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. This article provides an overview of the practical and technical details as well as the utility of BAT in diagnosis and management of allergic diseases.

Published
2016

39. Aged mice display altered numbers and phenotype of basophils, and bone marrow-derived basophil activation, with a limited role for aging-associated microbiota

Author

Floris Fransen, Adriaan A. van Beek, Paul de Vos, Edward F. Knol, Huub F. J. Savelkoul, Ben Meijer, Man, Biomaterials and Microbes (MBM), Translational Immunology Groningen (TRIGR), and Immunology

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, Aging, Immunology, Spleen, Celbiologie en Immunologie, chemical and pharmacologic phenomena, Biology, Basophil, lcsh:Geriatrics, HEMATOPOIESIS, 03 medical and health sciences, 0302 clinical medicine, IL-4 PRODUCTION, parasitic diseases, SURVEILLANCE, medicine, Journal Article, PROMOTE, Bone marrow, Alistipes, IN-VIVO, Research, Microbiota, Immunity, RECOGNITION, Akkermansia, hemic and immune systems, biology.organism_classification, Basophils, Basophil activation, Haematopoiesis, Ageing, lcsh:RC952-954.6, 030104 developmental biology, medicine.anatomical_structure, Cell Biology and Immunology, CELLS, biology.protein, WIAS, Antibody, lcsh:RC581-607, 030215 immunology, RESPONSES
Abstract

Background: The influence of age on basophils is poorly understood, as well as the effect of aging-associated microbiota on basophils. Therefore, we studied the influence of aging and aging-associated microbiota on basophil frequency and phenotype, and differentiation from basophil precursors.Results: Basophils became more abundant in bone marrow (BM) and spleens of 19-month-old mice compared with 4-month-old mice. Aged basophils tended to express less CD200R3 and more CD123, both in BM and spleen. Differences in microbiota composition with aging were confirmed by16S sequencing. Microbiota transfers from young and old mice to germ-free recipients revealed that CD11b tended to be lowered on splenic basophils by aging-associated microbiota. Furthermore, abundance of Alistipes, Oscillibacter, Bacteroidetes RC9 gut group, and S24-7 family positively correlated and CD123 expression, whereas Akkermansia abundance negatively correlated with basophils numbers.Subsequently, we purified Fc epsilon RI(+)CD11c(-)CD117(-) BM-derived basophils and found that those from aged mice expressed lower levels of CD11b upon stimulation. Higher frequencies of IL-4(+) basophils were generated from basophil precursors of aged mice, which could be reproduced in basophils derived from germ-free recipients of aging-associated microbiota.Conclusions: Collectively, these results show the influence of aging on basophils. Furthermore, this study shows that aging-associated microbiota altered activation of BM-derived basophils in a similar fashion as observed in BM-derived basophils from aged mice.

Published
2018

40. EAACI Guidelines on Allergen Immunotherapy:Allergic Rhinoconjunctivitis

Author

Ralph Mösges, Graham Roberts, Jamie Wilkinson, P W Hellings, Eckard Hamelmann, E. Angier, Désirée Larenas-Linnemann, Andrew James Williams, Sandra Y. Lin, Olympia Tsilochristou, Steffen Lau, Constantinos Pitsios, Cezmi A. Akdis, Lewei Zhang, Montserrat Fernandez-Rivas, Ioana Agache, Marek Jutel, P. Maggina, Carsten B. Schmidt-Weber, S. Dhami, Lars Jacobsen, Antonella Muraro, Dermot Ryan, Ruby Pawankar, I. J. Ansotegui, Gunter J. Sturm, G. Rotiroti, Elideanna Pastorello, Frans Timmermans, R. van Ree, Stefania Arasi, Susanne Halken, Edward F. Knol, Moises A. Calderon, Cemal Cingi, Aziz Sheikh, J. N. G. Oude Elberink, Giovanni B. Pajno, Martin Penagos, Oliver Pfaar, Stephen R. Durham, Jean-Luc Fauquert, R. Gerth van Wijk, Eva-Maria Varga, Margitta Worm, Internal Medicine, Erasmus MC other, Ear, Nose and Throat, AII - Inflammatory diseases, APH - Personalized Medicine, APH - Global Health, Experimental Immunology, AII - Amsterdam institute for Infection and Immunity, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Allergy, Allergen immunotherapy, medicine.medical_specialty, Immunology, Population, Placebo-controlled study, SHORT-TERM IMMUNOTHERAPY, COST-EFFECTIVENESS ANALYSIS, Allergen immunotherapy, Allergic conjunctivitis, Allergic rhinitis, Allergy, Rhinoconjunctivitis, Immunology and Allergy, Immunology, PLACEBO-CONTROLLED TRIAL, law.invention, DOUBLE-BLIND, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Randomized controlled trial, SUBLINGUAL-SWALLOW IMMUNOTHERAPY, law, medicine, HOUSE-DUST-MITE, Immunology and Allergy, Humans, 030212 general & internal medicine, Intensive care medicine, education, Conjunctivitis, Allergic, education.field_of_study, allergic rhinitis, business.industry, PERSISTENT SUBCUTANEOUS NODULES, rhinoconjunctivitis, GRASS-POLLEN IMMUNOTHERAPY, Guideline, RANDOMIZED CONTROLLED-TRIAL, medicine.disease, allergy, Rhinitis, Allergic, Allergic conjunctivitis, allergic conjunctivitis, 030228 respiratory system, Desensitization, Immunologic, allergen immunotherapy, ADVERSE SYSTEMIC REACTIONS, business
Abstract

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology and it may have a disease modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergy Immunotherapy". It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass-tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children. This article is protected by copyright. All rights reserved

Published
2018

41. Sensitization to PR-10 proteins is indicative of distinctive sensitization patterns in adults with a suspected food allergy

Author

André C. Knulst, Mark A. Blankestijn, Henny G. Otten, Thuy My Le, Rob J.B. Klemans, Edward F. Knol, and Heike Röckmann

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Intoxicative inhalant, Allergy, Immunology, Adult population, Storage proteins, 03 medical and health sciences, 0302 clinical medicine, Food allergy, medicine, Storage protein, Immunology and Allergy, PR-10, Sensitization, chemistry.chemical_classification, Food protein, business.industry, Research, RC581-607, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Specific IgE, 030228 respiratory system, chemistry, Concomitant, Immunologic diseases. Allergy, ImmunoCAP ISAC, business
Abstract

Background The extent of co-sensitization within and between food protein families in an adult population is largely unknown. This study aimed to identify the most frequently recognized components in the PR-10 and storage protein family, as well as patterns in (co-)sensitization, in a birch-endemic area. Methods Results of ImmunoCAP ISAC, performed during routine care in Dutch adult outpatients suspected of food allergy, were collected. Results A total of 305 patients were selected, aged 16–79 years (median 32 years). Sensitization to one or more PR-10 proteins was most frequent (74% of all subjects), followed by 35% to storage protein and 15% to nsLTPs. Within the PR-10 family, subjects were most often sensitized to Bet v 1 (73% of 305), Cor a 1.04 (72%) and Mal d 1 (68%). Sensitization to PR-10s from soy, celery and kiwi occurred distinctively less often ( 70%). Subjects sensitized to these ‘less common PR-10 proteins’ were sensitized to more food and inhalant components on the ISAC, compared to subjects sensitized to ‘common PR-10 proteins’ (median 22 vs 13 out of 112, p

Published
2017

42. Erratum to: Allergen immunotherapy for allergic rhinoconjunctivitis

Author

Vivian Maggina, Désirée Larenas Linnemann, Frans Timmermans, Ruby Panwankar, Oliver Pfaar, Pascal Demoly, Jamie Wilkinson, Eva-Maria Varga, Stephen R. Durham, Sandra Y. Lin, Ronald Gerth van Wijk, Sangeeta Dhami, Cemal Cingi, Aziz Sheikh, Margitta Worm, Luo Zhang, Hanneke Oude-Elberink, Giovanni Battista Pajno, Giuseppina Rotiroti, Eckard Hamelmann, Susanne Halken, Elideanna Pastorello, Edward F. Knol, Antonella Muraro, Peter Hellings, Graham Roberts, Lars Jacobsen, Ignacio J. Ansotegui, Andrew James Williams, Olympia Tsilochristou, Constantinos Pitsios, Ulugbek Nurmatov, Moises A. Calderon, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Montpellier (UM)

Subjects
Pulmonary and Respiratory Medicine, Protocol (science), medicine.medical_specialty, Allergen immunotherapy, business.industry, Published Erratum, Immunology, Section (typography), RC581-607, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Immunology and Allergy, Medicine, media_common.cataloged_instance, Medical physics, European union, Immunologic diseases. Allergy, Erratum, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, business, media_common
Abstract

The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic rhinoconjunctivitis.We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised.The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.

Published
2017

43. Serum biomarker profiles suggest that atopic dermatitis is a systemic disease

Author

Stefan Nierkens, Athula Herath, Carla A.F.M. Bruijnzeel-Koomen, Richard D. May, Tomas Mustelin, Edward F. Knol, Ian Strickland, Julia Drylewicz, Bret R. Sellman, Matthew A. Sleeman, Eszter Csomor, DirkJan Hijnen, Judith L. Thijs, Barbara Giovannone, and Marjolein S. de Bruin-Weller

Subjects
0301 basic medicine, Adult, Male, Systemic disease, Transgene, Immunology, Inflammation, Mice, Transgenic, Dermatitis, Atopic, 030207 dermatology & venereal diseases, 03 medical and health sciences, Mice, 0302 clinical medicine, Serum biomarkers, medicine, Immunology and Allergy, Animals, Humans, Asthma, business.industry, Atopic dermatitis, medicine.disease, Mice transgenic, 030104 developmental biology, Female, medicine.symptom, business, Biomarkers
Published
2017

44. Reply

Author

Yolanda Meijer, Francine C. van Erp, Bo Pontoppidan, Edward F. Knol, Hannah M. Kansen, André C. Knulst, and Cornelis K. van der Ent

Subjects
Allergy, medicine.medical_specialty, Clinical immunology, business.industry, Immunology, Allergy testing, Immunoglobulin E, medicine.disease, Outcome (game theory), humanities, Basophils, Family medicine, Immunology and Allergy, Medicine, Humans, Peanut Hypersensitivity, business, Child
Abstract

Refers to Shelly Rajput, Vibha Sharma, Stephen M. Hughes, Carol I. Ewing, Peter D. Arkwright Allergy testing in predicting outcome of open food challenge to peanut Journal of Allergy and Clinical Immunology, Available online 16 June 2017

Published
2017

45. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Georgios Rentzos, Esben Eller, Annick Mercenier, Magna Correia, Pedro Moreira, Linda Verrill, Mário Morais-Almeida, Frauke Schocker, Carsten Bindslev-Jensen, Ulrike Lehnigk, Andreas Frey, Lars Verschuren, Anna-Lena Bramstång Björk, Lene Heise Garvey, Elena Molina, Katrine L. Bøgh, J. L. van der Velde, Montserrat Alvaro, Phil Padfield, Niamh Brosnan, Nelly Gourdon-Dubois, Christian Harwanegg, Manuel Branco Ferreira, Songül Yürek, Amyra Ali Azamar Jácome, Rashid Amin, José Ramón Fernández Lorenzo, Kirsten Beyer, Florin-Adrian Secureanu, Charlotte Bernhard Madsen, Julie Galand, Claudia Pföhler, Rabea Reinert, Heinz Fehrenbach, Anton Hartmann, Maria Salas, Arne Homann, Rand Arnaout, Sarah Lindsley, Nerea Sarmiento Carrera, Patrícia Padrão, Berber Vlieg-Boerstra, Alkerta Ibranji, Benoît Sterling, Maria Auxiliadora Guerrero, Maria L. Baeza, Maurizio Tamburrini, Eva Untersmayr, Tanja Cirkovic Velickovic, Farrukh Sheikh, Sarah Kuntz, Sara Martínez, Kriti Gupta, Maria de Lurdes Torre, Yvonne Vergouwe, Ross Yarham, Faisal R. Bakhsh, Marta Vazquez-Ortiz, João Marcelino, Tullio Frediani, Ricardo Prata, Anna Kaarina Kukkonen, Gustavo Soldateli, Ines Mrakovčić-Šutić, Elodie Drumez, Cristina Ornelas, Maria Vazquez de La Torre, Renata Barros, Agata Szymkiewicz, Aneta Tomaszewska, Stefanie Rohwer, Charlotte Eisenmann, Adriana Muntean, Matteo Moretti, Johanna P. M. van der Valk, Birgit Quinting, Stefan Kabasser, David Gillick, Michał Przybyszewski, Grzegorz Sergiejko, Antonio Jorge Cabral, Alba Pablos-Tanarro, Robert Elfont, Marit Reitsma, Roxana Silvia Bumbăcea, Nelson Rosario, Maria Livia Bernardi, Cristiane N. Santos, Christian Radauer, Sandra Denery-Papini, Geert F. Houben, Nicolette W. de Jong, Marta Anda, Alexander Rohrbach, Teodorikez Wilfox Jimenez-Rodriguez, María Teresa Villalba, Karine Patient, Harmieke van Os-Medendorp, Kathrin Scherer, Marta Goñi Esarte, Svetlan Dermendzhiev, Jossie Garthoff, Michelle M. Epstein, Catherine Bertholet, Bruna Pultrini Aquilante, Didier G. Ebo, Roberta Aina, Jorge Kalil, Petri Kulmala, Lars K. Poulsen, Barbara Ballmer, H. Mary-Lene de Zeeuw-Brouwer, Karin Hoffman-Sommergruber, Winfried Leeman, Anne Miles, Nehad Gomaa, Maria Teresa Costantino, Evelyne Mangodt, Maria Konstantakopoulou, Rosa Jimenez, Attilio Francesco Speciani, Helga Magnusdottir, Inmaculada Sánchez-Machín, H. Kaddouri, Raquel Perez, Astrid Versluis, Anthony E. J. Dubois, Anja Koren Jeverica, Zdenka Barićev-Novaković, Joost Westerhout, A.M. Plaza, Júlio Oliveira, Pierre Lukas, Oksana Matsyura, Giuseppe Pingitore, Mira Silar, Huub F. J. Savelkoul, Urszula Samolinska-Zawisza, Chantal Brossard, Ana Reis Ferreira, Reiko Teshima, Serena Perna, Mariola Dietrich, Dirk Verhoeven, Fiona Kenna, Paloma Poza-Guedes, Cristobalina Mayorga, Pilar Hernandez, Roberto Bernardini, Roberto Berni Canani, Maria Francesca Patria, Mariana Vieru, Julie Locklear, Esther van Twuijver, Marina A. Kiseleva, H. Kim A. Brand, Gabriele Schulz, Ileana-Maria Ghiordanescu, Nikolaos G. Papadopoulos, Danijela Apostolovic, Maria del Mar Folqué, Eva Lasa, Mohammad Al Bahkali, Arianna Dondi, Sofia Kostoudi, Simon Rosenberg, Véronique Nève, Rumyana Yankova, Barbara Ballmer-Weber, Maria Jose Goikoetxea, María José Barasona Villarejo, Teija Dunder, Tina Vesel, Elisa Gritti, Marianne van Hage, Laure Castan, Etienne Beaudouin, Margherita Di Costanzo, Natalia Ukleja-Sokołowska, Matthew Sperrin, Paul Turner, Saskia Albroscheit, Rebeca Lopez, Sonja Posega Devetak, Francisca Palomares, Laetitia Sellam, Jennifer Hammond, Astrid G. Kruizinga, Konrad Furmanczyk, Patricia Macchiaverni, Olga Pakholchuk, I V Vorozhko, Ania Carsin, Aleksandar Bulog, Joris Mens, Bianca Balbino, James P. Hindley, Jaap H. Akkerdaas, Jonathan Hourihane, Hilde Cnossen, Tatyana A Popova, Rupert Schlags, Natalia Nenasheva, A. Ehrenberg, Sigurveig T. Sigurdardottir, Anna Iliopoulou, Clara Ippolito, Piotr Samel-Kowalik, Paloma Campo, Gador Bogas, Constantinos Pitsios, Sarah Grosche, Karla Leversia Borjas Aguilar, Amena Warner, Birgit Kalb, Lénaïck Dupuis, Harry J. Wichers, Diana Silva, Gabriele Piuri, Linus Grabenhenrich, Emanuel Sarinho, M. Eleonore Pettersson, Rodrigo Barderas, Gary Stiefel, E. N. Clare Mills, Lali Saginadze, Ruta Dubakiene, Francesca Cipriani, Mindy Tsai, Marina Themisb, Michela Ciancamerla, Rebecca Knibb, Ruperto González-Pérez, Marina Peredelskaya, André C. Knulst, Irene Berends, S N Denisova, Montserrat Fernandez-Rivas, Paolo Maria Matricardi, Daniel Sampaio, Giorgio Bedogni, Sira Miquel, Koen Smit, Stefania Arasi, Sylvia Osscini, Justine Courtois, Cristina Deaconu, Srdan Banac, Kirsten Hansen, Jennette Higgs, Charlotte Hands Plovdiv, Carlotta Povesi Dascola, Noe Ontiveros, Rik Schrijvers, Carla Mastrorilli, Maria Passioti, Sebastian Tschirner, Bjorn R. Ludviksson, Joana Caiado, Daniel Corbacho, Sophie Nutten, Agustin Madroñero, Marina Suárez Vergara, Boudewjin J. Kollen, Catherine J Nock, Johanna Rost, Agnieszka Lipiec, Skadi Kull, Geert Houben, Carlo Caffarelli, Jordi Roca-Ferrer, Bolesław Samoliński, Isabelle Cleach, Colette Larré, Aideen Byrne, Corinne Herouet-Guicheney, Jonas Lidholm, Vera Assmann, W. Marty Blom, Adriano Mari, Adam T. Fox, Giuseppe Crisafulli, Afke M. M. Schins, Anastasia Papadopoulou, Flávio Sano, Richard Cooke, Franziska Ruëff, L Jorjoliani, Rebekah Sayers, Anne-Marie Kochuyt, Borja Bartalomé, Anne Moneret-Vautrin, Juan Carlos Julia, Jelena Mihailovic, Katarzyna Pyrz, Kollen Boudewijn, Margherita Varini, Paolo Giordani, Claudia Alessandri, Johanna van der Valk, Antoine Deschildre, Mariam Tskhakaia, Rosina López-Fandiño, Omar Kheroua, Nicolette J. T. Arends, Alina Zbróg, Chung-Hsiung Huang, Andrea Wangorsch, Ulf Bengtsson, Jim Langridge, Dasha Roa-Medellín, Jose Ignacio Larco, Bert Popping, Ana Prieto del Prado, José Antonio Bácter Martos, Rita Nocerino, Sophia Watts, Elisa Haroun, Danilo Villalta, Lee A. Gethings, María Ángeles Algaba Mármol, Ewa Gawrońska-Ukleja, Cornelia Jansen, André Moreira, V A Revyakina, Robert Zacniewski, Xavier Domingo Miró, Francesco Macrì, Mayra de Barros Dorna, Akanksha Sharma, Stephen J. Till, Ali Almontasheri, Chrystyna Kalicinsky, Robbert Sutorius, Akila Rekima, Mark A. Blankestijn, Nicolette Arends, Chiara Pistoletti, Merima Bublin, Manuel Pereira-Barbosa, Reyna Simon, Martin Karjalainen, Sam Mehr, Tushar Banerjee, Carmen Riggioni, Bertrand Evrard, Antonio Carlos Pastorino, Lidia Ilènko, Nikolaos Douladiris, Miguel Vieira, Erik Wambre, Francisco Cabrera-Chavez, Nikos G. Papadopoulos, Piotr Humeniuk, Gert van Duijn, Francesco Zinno, Young-Ae Lee, Lisa Tuppo, Hans de Groot, Léon M.J. Knippels, Pawel Dubiela, Henrik Fomsgaard Kjaer, Andrea Vereda, Djamel Saidi, Kok Loong Ue, Henk Van Loveren, Maria Jose Rodriguez, Marta Lomikovska, Elodie Michaud, Josefina Cernadas, Carmen Ponce, Marysia Recto, Frances Smith, Hassan Al-Dhekri, Shinobu Sakai, Thomas Eiwegger, Ana Rodolfo, Diego Peroni, Nikki Edelbroek, Waltraud Suer, Jenny van Odijk, Irena Nedelea, Borja Bartolomé, Lauren Lissner, Marjeta Sedmak, Annette Jamin, Italo De Vitis, Bo Pontoppidan, Annabelle Capt, Diego G. Peroni, Susana Rodrigues, Juan Carlos López-Rodríguez, David Endesfelder, Lesya Besh, Danila Zennaro, Charlotte G. Mortz, Kati Palosuo, María José Torres, Esozia Arroabarren, Lynne Regent, Laura Valdesoiro Navarrete, Ana Molina, Agha Rehan Khaliq, Phil Couch, Ana Miranda, Thomas Marichal, Riccardo Asero, Denise Borges, Dikla Pivko Levy, Miriam Palacios, Mireille Eb, Stephen J. Galli, Karin Hoffmann-Sommergruber, Anna Gudrun Vidarsdottir, Ifigenia Sfika, André Wolterbeek, Mauro Calvani, Edward F. Knol, Joyce A. M. Emons, Anne-Marie Oomkes-Pilon, Montserrat Bosque García, Daniel Lozano-Ojalvo, Filip Raciborski, Deirdre Galloway, Nanna Juel-Berg, Margareta Brandt Gertmo, Cornelia Bergmayr, Rob Klemans, Juliane Gregersen, Yolanda Meijer, Bettina Brix, Susanne Lau, Karine Adel-Patient, Hanneke van der Kleij, Mareike Price, Jean-Louis Mege, Lizalet Oosthuizen, Agurtzane Bilbao, Indre Butiene, Antonino Romano, Colin Barber, Rosana Camara Agondi, Nour Baïz, Soraya Ainad Tabet, Peter Korošec, Laurian Jongejan, Francine C. van Erp, José Pedro Moreira Silva, Nandinee Patel, Jaime Lozano, Prescilla V. Jeurink, Artur Walkiewicz, Bryan M. Harvey, Tiina J. Kauppila, Aida Semic-Jusufagic, Marianna Murdjeva, Miren Arteaga, Y. Bouferkas, Geunwoong Noh, Henny G. Otten, Sabine Dölle, Christopher Munro, O Dominguez, Gerard H. Koppelman, Leonieke N. van Veen, Vasti Iancu, Georg Mitterer, Patrizia Polverino de Laureto, Juliane Schulz, Ewa Ternesten Hasseus, Caroline Zimmermann, Ivona Barcievic-Jones, Shira Benor, Susanne Schwarz, Eun Ha Jang, Josefina Rodrigues Cernadas, Tadej Avcin, Joseph L. Baumert, Pernille Winther, Stéphane Leteurtre, Gabriela Canto, Louise J Michaelis, Jorge Alvarez, Gabriel Gastaminza, Michela Carola Speciani, Rute Gonçalves, Leire Dopazo, Evgen Benedik, Susanne C. Diesner, Luc S. De Clerck, A. Wesley Burks, Maurits S. van Maaren, Salvatore Tripodi, Philippe Aubert, Kamel Eddine El Mecherfi, Aline B. Sprikkelman, Ana Prieto, Margitta Worm, Edyta Krzych, Maja Krstic, Iride Dello Iacono, Melanie Cap, Alf Weimann, Maria Nassiri, Niels Röckendorf, Vladyslava Barzylovych, Marcia C. Mallozi, Pierre Bruhns, Jeanette Fisker Trandbohus, Ekaterini Papadopoulou, Vicente Albendiz, Timothy Watts, Uta Jappe, Javier Moreno, Maria Carmen Verga, Beatriz Secades Barbado, Carmen Di Scala, Roy Gerth van Wijk, Vladimir Mićović, Esther Barrionuevo, Giampaolo Ricci, Luisa Galindo, Ana Paula Beltran Moschione Castro, Oona Mustonen, Jia Yin, Lucia Caminiti, Jorge Esparza-Gordillo, N Adamia, Anna-Maija Hanni, Romy Gadisseur, Stefano Luccioli, Regina Treudler, Rosetta Ferrara, M. Guendouz, Jaakko Yrjänä, Philipp Starkl, Premendra D. Dwivedi, Javier Cuesta-Herranz, Johan Garssen, Ekaterini Goudouris, Sridevi Muralidharan, Kate Grimshaw, Carolina Sanchez Aranda, Ioana Maris, Manzoor Ahmed, Hajime Karasuyama, Stephanie Claus, Chantal Agabriel, Karen English, Dorien Van Ginkle, Eleonora Savi, Loredana Chini, Ine I. Decuyper, Sabine Schnadt, Valérie Trendelenburg, Jean-Luc Fauquert, Maurizio Mennini, Nikolaos Mikos, Ana Célia Costa, Steve L. Taylor, A. A. Schoemaker, Sara Abián, Margo M. Hagendorens, Andrea Di Rienzo Businco, Melina Makatsori, Eugénia Matos, Lucy Walker, Nikolaos A. Kitsioulis, David Alejandro Mendoza Hernández, Maria Starkhammar, Djordje Filipovic, Aine Adams, Mukul Das, Sonsoles Intente-Herrero, Natalia Blanca López, Marek L. Kowalski, Diana Deleanu, Bernard P. Mahon, Jean-Michel Wal, Lucia Decastelli, Mihaela Popescu, Aimee Lou Nano, Eva Batanero, Tong-Rong Jan, Yolanda Puente, Jacek Borowicz, Aimée Dorkenoo, J. Östling, Mashary Altamimi, Michel Neunlist, Zerrin Yalvaç, Sonia Ricò, Wentong Xue, Linda Cosenza, David C. A. Candy, Robert D. Voyksner, Montserrat De Prada, Abdulhadi Al-Qahtani, Sébastien Holvoet, Wolf-Meinhard Becker, Meropi D. Kontogianni, Bruno Pereira, F. Pineau, Eva Corbet, Kirsten Mehlig, Rosella De Poi, Jolanda H. M. van Bilsen, José Luís Plácido, Hans-Jørgen Malling, Chia-Chi Wang, Philip Couch, Kerrie Kirk, Agata Michalska, Sylke Rietz, Mariya Ivanovska, Victor Matheu-Delgado, Carl Hamsten, Francisca Gómez, Neusa Falbo Wandalsen, Mika J. Mäkelä, Tatyana Sentsova, Kristian Bravin, Philippe Delahaut, Hervé Bernard, Leonor Carneiro-Leão, Michele Miraglia del Giudice, Elena D. Kuvshinova, Jochen Behrends, Caroline Klingebiel, Meta Accetto, Claire Mills, Mariona Pascal, Miguel García Domínguez, Huan Rao, Carmen Saviana Ganea, Umberto Pelosi, Stefano Pattini, Bodo Niggemann, Annamaria Bianchi, Laura Martín-Pedraza, Anna Selby, Cristina Bueno, Stefan Vieths, Luis Felipe Ensina, Florin-Dan Popescu, Antonio Fernandez, Soren Wille, Erna Van Hoeyveld, Carina Kelleher, Athina L. Van Gasse, Anders Blom Jensen, Zorica Zivkovic, Moshe Ben-Shoshan, Sara Pereiro Fernández, Ronald van Ree, Antima Banerjee, Pablo Merida, Mandy Ziegert, Barbara Wróblewska, Morten Christensen, Gador Gomez, Pablo San Segundo-Acosta, Khaled Messaoudi, Anne-Sofie Ravn Ballegaard, Mikael Kuitunen, David Luyt, Vito Sabato, Nesrine Zaabat, Svitlana Zubchenko, Julien Labreuche, Elin Lustig, Katharina Blumchen, Guillaume Pouessel, Ana Fiandor, Stéphanie Lejeune, Paola Dignetti, Helen Brown, Anastasia Cirisano, Evangelia Kompoti, Anna Sokolova, Mercedes Escarrer Jaume, Shan Deng, Dirceu Solé, Chiara Fiamingo, Alessandro Travaglini, Nicolas Gaudenzio, Zbigniew Bartuzi, Antonia Rojas, Roberta Olcese, Nanju Alice Lee, Sandra Brandhoff, Lucien F. Harthoorn, Anna Maria Szyc, Andrea Costanzi, Sabine Pfeifer, Emiliano De Dominicis, Chiara Rafaiani, Yin-Hua Cheng, Elida Nikolla, Ignacio García Núñez, Diego Faggian, Lieve Coorevits, Ayelet Rimon, Erika Jensen-Jarolim, Jacqueline J.M. Castenmiller, Kristin Verbeke, Sean Bennett, Paraskevi Xepapadaki, Glauce Hiromi Yonamine, Anna Wawrzeńczyk, Rusudan Karseladze, Emmanouil Manousakis, Fiona Ward, Ivana Filipovic, Marie Bodinier, Viviana Moschese, Pedro Giavina Bianchi, Alice Coimbra, Alena Berger, Anton A. Shekhetov, Monica Maćków, Philippe Egenmann, Oscar Asensio, Lidia Hanna Markiewicz, Chun-Wei Tung, Zsolt Szépfalusi, Jan Knol, Frits Koning, Carolina S. Aranda, Annick Bastiaensen, Giovanni Battista Pajno, Leticia Pérez-Rodríguez, Ewout W. Steyerberg, Riccardo Sibilano, Valérie Verhasselt, Roberta Lupi, Lukasz Sokolowski, Adam Wawrzeńczyk, Dimitris I. Mitsias, Andreia Forno, Antoine Magnan, Christian Schwager, Ioanna Manolaraki, Alessandro Fiocchi, Tanja Rouhani Rankouhi, Carla Jones, Ana Pereira, Hannah M. Kansen, Michael Clausen, D. Bignardi, Assad M. Butt, Julie C. Locklear, Katrine Lindholm Bøgh, Valery Muhortnich, María Teresa Giner, Juan Miguel Garcia, Maria Luisa Somoza, Raditsa Sokolova, Maria Pasioti, Mirjana Zupancic, Joana Vitte, Duncan Brown, Arnaldo Porto, M. Turfkruyer, Lau Fabricius Larsen, Filipe Benito-Garcia, Mayra Coutinho Andrade, Meltem Ugras, Ingrid Sutic, Rand K. Arnaout, Etienne Cavalier, Marta Neto, Grégory Bouchaud, Elena Varin, Bushra Javed, Carla Camerotto, Monica Bronkowska, Cristiano Caruso, Luís Amaral, Jackeline F. Motta, Sahar Elshorbagi, Cornelis K. van der Ent, Alexandra Rodrigues, Silvia Peveri, Juan Heber Castellanos, Muriel Totis, Joan Bartra, Gjustina Loloci, Ivana Giangrieco, Ekaterina Khaleva, Joaquín Navarro, Kayoko Matsunaga, Jlenia Fresta, Jonathan O'b Hourihane, Sabina Bijlsma, Ana Rodriguez-Fernandez, Rosita Aitoro, Daniela Manila Bianchi, Rosa Jimenez-Feijoo, Mario Plebani, Marleen T. J. Van Ampting, Anthony E.J. Dubois, Clémence Mordacq, Simone Frediani, Martin Chapman, Helena Larramona, Fabrícia Carolino, Yanne Boloh, Ivona Baricevic-Jones, Mathilde Claude, Caroline Thumerelle, Päivi Vähäsarja, Mareen R. Datema, Abdullah Alfhaid, Diana Perez Alzate, Laura Santos-Diez, Graham King, Maria Teresa Guerra Perez, Jean-Marie Renaudin, Frieke Kuper, Josué Alejandro Huertas Guzmán, Harry Wichers, Thomas Keil, A. Haddi, Jennifer Santos, Regina Selb, Aida del Campo García, Maria Basagaña, Valentino Pavišić, Angela Simpson, Chris H. Bridts, Susana Piedade, Silvia Gallina, Isabella Pali-Schöll, Inês Pádua, Margaretha A. Faber, Frédéric de Blay, Luís Câmara Pestana, Ben Remington, Anna S. Pelkonen, Sandra Lucarelli, Ivana Šutić, Olivier Tranquet, Montserrat López Onieva, Antonio Amoroso, Paola Minale, Katia Basello, George Du Toit, Daniela Adriano, Adnan Custovic, Zbikowska-Gotz M, Domingo Barber, Inmaculada Doña, Christine Breynaert, Hanan Sharif, Manon M. Oude Nijhuis, Sandra Denery, Bertine M. J. Flokstra-de Blok, Rinkesh Kumar Gupta, Pieter-Jan de Kam, Dianne E. Campbell, Carmen M. D'Amelio, Nunzia Maiello, Ingo Marenholz, José María Ignacio García, Helen Lindqvist, Lilian Moraes, Cleonir Lui de Moraes Beck, Eunice Dias de Castro, Cono Casale, Barbara Majkowska-Wojciechowska, Maria Petrodimopoulou, Andrea Mikkelsen, Hub P. J. M. Noteborn, Hulya Ercan Saricoban, Moira Austin, Martinus Løvik, Graham Roberts, Isabella Annesi-Maesano, Aeilko H. Zwinderman, Sigrun H. Lund, Anouska D. Michelsen-Huisman, Fernando Bandrés Sánchez-Cruz, Francisco Javier Ruano, Valérie Liabeuf, Eman Madbouly, Pasquale Comberiati, Maria Isabel Garcimartin, Stephan Scheurer, Inna A. Larkova, Jean Tratt, Renata Rodrigues Cocco, Younes Belabbas, Lorella Paparo, Elizabeth Griffiths, Gian Lodovico Rapaccini, Audrey Dunn Galvin, Zizi Cojocariu, Isidor Hutteger, Claire Claverie, S.M. Nedelska, Anna Kuklinska-Pijanka, Jenny Badas, Mónica Piquer, Iztok Devetak, A.K.F. Gushken, Frans Timmermans, Adriana Machinena, Francisco Javier Monteseirin, Amaranta Traversa, Fátima Cabral Duarte, Tomaž Poredoš, Peter Meyer, Cristina Arêde, Rosa Muñoz-Cano, Barbara Pfitzner, Alejandro Joral, Juan Carlos Daza, Laurent L. Reber, Olga Chernyak, and Maria Antonetta Ciardiello

Subjects
Pulmonary and Respiratory Medicine, Allergy, medicine.medical_specialty, 030504 nursing, business.industry, Immunology, RC581-607, medicine.disease, Meeting Abstracts, 03 medical and health sciences, 0302 clinical medicine, Food allergy, 030225 pediatrics, Family medicine, medicine, Immunology and Allergy, Immunologic diseases. Allergy, 0305 other medical science, business, Anaphylaxis
Published
2017

46. Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic overview of systematic reviews

Author

Ruby Panwankar, Luo Zhang, Hanneke Oude-Elberink, Désirée Larenas-Linnemann, Giuseppina Rotiroti, Frans Timmermans, Lars Jacobsen, Eckard Hamelmann, Stephen R. Durham, Roy Gerth van Wijk, Sangeeta Dhami, Susanne Halken, Giovanni Battista Pajno, Aziz Sheikh, Sandra Y. Lin, Vivian Maggina, Ignacio J. Ansotegui, Oliver Pfaar, Andrew James Williams, Antonella Muraro, Constantinos Pitsios, Eva M. Varga, Ulugbek Nurmatov, Margitta Worm, Moises A. Calderon, Peter Hellings, Graham Roberts, Elideanna Pastorello, Cemal Cingi, Edward F. Knol, Stefania Arasi, Jamie Wilkinson, Olympia Tsilochristou, Internal Medicine, Erasmus MC other, and Clinical Genetics

Subjects
Pulmonary and Respiratory Medicine, Allergen immunotherapy, medicine.medical_specialty, Allergy, IMPACT, Hay fever, Immunology, Alternative medicine, CHILDREN, Allergic rhinitis, Allergic rhinoconjuctivitis, Rhinitis, Review, RECOMMENDATIONS, 03 medical and health sciences, 0302 clinical medicine, SUBCUTANEOUS IMMUNOTHERAPY, medicine, Journal Article, Immunology and Allergy, QUALITY, In patient, 030212 general & internal medicine, Intensive care medicine, METAANALYSIS, Asthma, Science & Technology, business.industry, RHINITIS, RC581-607, medicine.disease, EFFICACY, R1, Checklist, Critical appraisal, Systematic review, 030228 respiratory system, SUBLINGUAL IMMUNOTHERAPY, ASTHMA, Immunologic diseases. Allergy, business, Life Sciences & Biomedicine
Abstract

Background The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the effectiveness, safety and cost-effectiveness of AIT for ARC. Methods We undertook a systematic overview, which involved searching nine international biomedical databases from inception to October 31, 2015. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme (CASP) Systematic Review Checklist for systematic reviews. Data were descriptively synthesized. Results Our searches yielded a total of 5932 potentially eligible studies, from which 17 systematic reviews met our inclusion criteria. Eight of these were judged to be of high, five moderate and three low quality. These reviews suggested that, in carefully selected patients, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy resulted in significant reductions in symptom scores and medication requirements. Serious adverse outcomes were rare for both SCIT and SLIT. Two systematic reviews reported some evidence of potential cost savings associated with use of SCIT and SLIT. Conclusions We found moderate-to-strong evidence that SCIT and SLIT can, in appropriately selected patients, reduce symptoms and medication requirements in patients with ARC with reassuring safety data. This evidence does however need to be interpreted with caution, particularly given the heterogeneity in the populations, allergens and protocols studied. There is a lack of data on the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT. We are now systematically reviewing all the primary studies, including recent evidence that has not been incorporated into the published systematic reviews. Electronic supplementary material The online version of this article (doi:10.1186/s13601-017-0159-6) contains supplementary material, which is available to authorized users.

Published
2017

47. Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis

Author

Alexandra F. Santos, Giovanni Battista Pajno, Lars K. Poulsen, Edward F. Knol, Stefania Arasi, Kari C. Nadeau, Kirsten Beyer, R. van Ree, Liam O'Mahony, G. Du Toit, Carsten Bindslev-Jensen, Aziz Sheikh, Montserrat Alvaro-Lozano, Hugh A. Sampson, Ulugbek Nurmatov, M. Ebisawa, Cansin Sackesen, Antonella Muraro, S. Dhami, Philippe Eigenmann, Graham Roberts, Frans Timmermans, Nikolaos G. Papadopoulos, Montserrat Fernandez-Rivas, Wesley Burks, Mika J. Mäkelä, and Cezmi A. Akdis

Subjects
0301 basic medicine, Peanut allergy, Desensitization, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Odds Ratio, Immunology and Allergy, Allergens/administration & dosage, ddc:618, 3. Good health, Treatment Outcome, Meta-analysis, sustained unresponsiveness, Immunoglobulin E/immunology, Immunologic/methods, Food Hypersensitivity, safety, medicine.medical_specialty, Allergen immunotherapy, Food/adverse effects, Immunology, desensitization, Allergens/administration & dosage/immunology, 03 medical and health sciences, Food allergy, Internal medicine, Desensitization, Immunologic/methods, medicine, Animals, Humans, Adverse effect, Immunology and Allerg, food allergy, Sublingual Immunotherapy, business.industry, allergen immunotherapy, desensitization, food allergy, safety, sustained unresponsiveness, Immunology and Allerg, Immunology, Allergens, Immunoglobulin E, medicine.disease, 030104 developmental biology, 030228 respiratory system, Desensitization, Immunologic, Food, Egg allergy, Relative risk, allergen immunotherapy, Quality of Life, Food Hypersensitivity/immunology, business, Food Hypersensitivity/immunology/therapy
Abstract

BACKGROUND:The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy.METHODS:We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses.RESULTS:We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses.CONCLUSIONS:AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.

Published
2017

48. Erratum to : Allergen immunotherapy for IgE-mediated food allergy: protocol for a systematic review

Author

Giovanni Battista Pajno, Kirsten Beyer, Alexandra F. Santos, Sangeeta Dhami, Ronald van Ree, Antonella Muraro, Liam O'Mahony, Frans Timmermans, Graham Roberts, Lars K. Poulsen, Hugh A. Sampson, Kari C. Nadeau, Carsten Bindslev-Jensen, Mika J. Mäkelä, Montserrat Fernandez-Rivas, Philippe Eigenmann, Wesley Burks, Ulugbek Nurmatov, Nikolaos G. Papadopoulos, Cezmi A. Akdis, Cansin Sackesen, George Du Toit, Motohiro Ebisawa, Aziz Sheikh, Montserrat Alvaro-Lozano, Edward F. Knol, and University of Zurich

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Allergen immunotherapy, Allergy, Published Erratum, Immunology, 610 Medicine & health, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Ige mediated, 10183 Swiss Institute of Allergy and Asthma Research, Food allergy, medicine, Immunology and Allergy, media_common.cataloged_instance, European union, media_common, Protocol (science), 2403 Immunology, ddc:618, business.industry, RC581-607, medicine.disease, 3. Good health, 030228 respiratory system, 2740 Pulmonary and Respiratory Medicine, Family medicine, 2723 Immunology and Allergy, Immunologic diseases. Allergy, business
Abstract

Unfortunately this article [1] was published with an error in the Funding section. The BM4SIT project is not acknowledged. This section should be corrected to the below: Funding EAACI and the BM4SIT project (Grant Number 601763) in the European Union’s Seventh Framework Programme FP7.

Published
2017

49. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: An EAACI Position Paper

Author

Adam Chaker, Carsten B. Schmidt-Weber, Jörg Kleine-Tebbe, Moises A. Calderon, Stephen J. Till, Pascal Demoly, M. Akdis, Mohamed H. Shamji, Lars Jacobsen, Oliver Pfaar, Stephen R. Durham, Jasper H. Kappen, Erika Jensen-Jarolim, Rudolf Valenta, Edward F. Knol, Lars K. Poulsen, and Barbara Bohle

Subjects
0301 basic medicine, Allergen immunotherapy, Allergy, Immunology, Provocation test, Immunoglobulin E, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, Humans, Asthma, Conjunctivitis, Allergic, biology, Allergen Immunotherapy, Basophil Activation, Biomarkers, Ige-fab, Igg4, business.industry, Allergens, medicine.disease, Prognosis, Rhinitis, Allergic, Lymphocyte Subsets, Basophils, Clinical trial, Basophil activation, 030104 developmental biology, Treatment Outcome, 030228 respiratory system, Desensitization, Immunologic, Immunoglobulin G, biology.protein, Biomarker (medicine), Cytokines, business
Abstract

Background Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. Method The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). Results All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed. Conclusions It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.

Published
2017

50. Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis

Author

Antonella Muraro, Martin Penagos, Elide A. Pastorello, Lars Jacobsen, Arnav Agarwal, Hadar Zaman, Edward F. Knol, Stefania Arasi, Graham Roberts, Carsten B. Schmidt-Weber, Eckard Hamelmann, Giuseppina Rotiroti, Ulugbek Nurmatov, H. N. G. Oude Elberink, Sandra Y. Lin, Jamie Wilkinson, R. Mösges, Stephen R. Durham, I. J. Ansotegui, Moises A. Calderon, P W Hellings, Lewei Zhang, Tahir Mehmood Khan, Cemal Cingi, Miqdad Asaria, Eva-Maria Varga, Andrew James Williams, Olympia Tsilochristou, Susanne Halken, Constantinos Pitsios, Margitta Worm, Paraskevi Maggina, G. Netuveli, R. Gerth van Wijk, S. Dhami, Giovanni Battista Pajno, Ruby Panwankar, Désirée Larenas-Linnemann, Frans Timmermans, Aziz Sheikh, Oliver Pfaar, Internal Medicine, Erasmus MC other, and Clinical Genetics

Subjects
0301 basic medicine, Allergy, Databases, Factual, Conjunctivitis, Allergic/therapy, Placebo-controlled study, Review, PLACEBO-CONTROLLED TRIAL, sublingual, law.invention, 0302 clinical medicine, Randomized controlled trial, Quality of life, QUALITY-OF-LIFE, law, HOUSE-DUST-MITE, Immunology and Allergy, Conjunctivitis, Allergic, allergen, allergen immunotherapy, allergic rhinoconjunctivitis, subcutaneous, sublingual, Immunology and Allergy, Immunology, DOUBLE-BLIND-PLACEBO, Cost-effectiveness analysis, Rhinitis, Allergic, Seasonal/therapy, RANDOMIZED CONTROLLED-TRIAL, Meta-analysis, subcutaneous, allergen, Allergen immunotherapy, medicine.medical_specialty, Immunology, SHORT-TERM IMMUNOTHERAPY, COST-EFFECTIVENESS ANALYSIS, 03 medical and health sciences, Allergens/immunology, SUBLINGUAL-SWALLOW IMMUNOTHERAPY, Internal medicine, Desensitization, Immunologic/methods, medicine, Journal Article, Humans, STANDARDIZED 5-GRASS-POLLEN EXTRACT, business.industry, Rhinitis, Allergic, Seasonal, allergic rhinoconjunctivitis, Allergens, medicine.disease, Discontinuation, 030104 developmental biology, 030228 respiratory system, Desensitization, Immunologic, allergen immunotherapy, GRASS-POLLEN EXTRACT, business
Abstract

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. In order to inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic rhinoconjunctivitis METHODS: We searched 15 international biomedical databases for published, in progress and unpublished evidence. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. RESULTS: We identified 5932 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95%CI -0.63, -0.42), medication (SMD -0.37, 95%CI -0.49, -0.26) and combined symptom and medication (SMD -0.49, 95%CI -0.69, -0.30) scores whilst on treatment that were robust to pre-specified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, this suggesting a benefit in relation to symptom scores. CONCLUSIONS: AIT is effective in improving symptom, medication and combined symptom and medication scores in patients with allergic rhinoconjunctivitis whilst on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy. This article is protected by copyright. All rights reserved.

Published
2017

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