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1. 75% negative skin test results in patients with suspected hypersensitivity to beta-lactam antibiotics: Influencing factors and interpretation of test results

Author

Lukas Joerg, MD, Susann Hasler, MD, Anna Gschwend, PhD, Cordula Meincke, MD, Thierry M. Nordmann, PhD, Martin Glatz, MD, Michelle Heilig, BSc, Benno Schnyder, MD, Arthur Helbling, MD, and Peter Schmid-Grendelmeier, MD

Subjects
Drug hypersensitivity, Drug allergy, Beta-lactams, Penicillins, Amoxicillin, Cephalosporins, Immunologic diseases. Allergy, RC581-607
Abstract

Background: The diagnostic approach for beta-lactam (BL) drug hypersensitivity reactions (DHR) is based on the history, clinical signs, skin tests (ST), in vitro tests, and drug provocation tests (DPT). The aim of this study was to assess the performance of an allergy workup with ST in a real-world use. Methods: In this cross-sectional study the rate of positive ST in subjects with suspected DHR to penicillins and cephalosporins was investigated. Of special interest were correlations of ST positivity: 1) to the time intervals between index reaction and the allergic work-up, 2) time interval from drug exposure to the onset of signs, 3) pattern of manifestation in delayed DHR and involvement of test area in the index reaction, and 4) potential advantage of patch testing in delayed DHR. Results: 175 patients were included between January 2018 and April 2019 (63.4% female), 45 (25.7%) with immediate DHR manifestation and 130 with delayed DHR manifestation (74.3%). A total of 44 patients (25.1%) had a positive ST (immediate DHR 37.8% versus 20.0% in delayed DHR). ST positivity decreased in both groups after 3 years from 47.8% [95%CI 29.2–67] to 23.5% [95%CI 9.6–47.3] in immediate DHR and 23.0% [95%CI 15-4-32.9] to 12.9% [95%CI 5.1–28.9] in delayed DHR. The proportion of positive ST was higher in patients with more severe forms of delayed DHR, and in subjects with a shorter latency period of onset of symptoms after drug exposure: 0-3d: 29.5% [95%CI 19.6–41.9] vs. >3d: 11.6% [95%CI 6.0–21.2]). No sensitization was shown in delayed urticaria or angioedema. ST done outside the skin area involved during the index reaction were negative in all cases (0/38 vs. 26/84 in cases with involved area). The combination of patch test and intradermal test (IDT) revealed an additional positive result in 2/77 cases. Additional in vitro testing reduced the proportion of negative test results to 72%. Conclusion: In most patients with negative test results, we could not clarify the cause of the BL-associated adverse events even with further investigations (including DPT). How to prevent new drug-induced adverse events in such patients has hardly been investigated yet. Corresponding cohort studies could improve the data situation.

Published
2021
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2. Specific Immunotherapy in a Pollen-Allergic Patient With Human Immunodeficiency Virus Infection

Author

Urs C. Steiner, MD, Hansjakob Furrer, MD, and Arthur Helbling, MD

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Background According to the World Health Organization position paper, immunodeficiency such as human immunodeficiency virus (HIV) infection is a relative contraindication for specific immunotherapy (SIT). Since the introduction of highly active antiretroviral therapy, a significant reconstitution of immune competence in individuals with HIV is possible.Case Report In a 52-year-old man, HIV infection was diagnosed in 1987. Antiretroviral therapy was started in 1998. He presented himself in July 2001 because of an increasingly severe seasonal rhinoconjunctivitis. Symptoms were not sufficiently alleviated by various antiallergic drugs.Results The investigations showed a relevant sensitization to tree pollens. Specific immunotherapy with a tree pollen mix (hazel, birch, ash, and alder, 25% each) was started in November 2001. Viral load at this time was less than 50 copies/mL, the CD4+ cell count was 307/μL. Therapy was given in monthly intervals until mid-April 2005 without any side effects. Viral load and CD4+ cell counts did not change during SIT. Clinically, rhinoconjunctivitis was experienced only intermittently and symptom relief was almost 90%.Conclusions This report indicates that in patients with well-controlled HIV infection on highly active antiretroviral therapy, SIT with pollen extracts is a potential and successful therapeutic option. Keywords: human immunodeficiency virus, pollen allergy, respiratory allergy, allergy treatment, specific immunotherapy

Published
2009
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3. Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency

Author

Annaïse J. Jauch, Olivier Bignucolo, Sayuri Seki, Marie Ghraichy, Ottavia M. Delmonte, Valentin von Niederhäusern, Rebecca Higgins, Adhideb Ghosh, Masako Nishizawa, Mariko Tanaka, Adrian Baldrich, Julius Köppen, Julia R. Hirsiger, Robin Hupfer, Stephan Ehl, Anne Rensing-Ehl, Helmut Hopfer, Spasenija Savic Prince, Stephen R. Daley, Florian A. Marquardsen, Benedikt J. Meyer, Michael Tamm, Thomas D. Daikeler, Tamara Diesch, Thomas Kühne, Arthur Helbling, Caroline Berkemeier, Ingmar Heijnen, Alexander A. Navarini, Johannes Trück, Jean-Pierre de Villartay, Annette Oxenius, Christoph T. Berger, Christoph Hess, Luigi D. Notarangelo, Hiroyuki Yamamoto, and Mike Recher

Subjects
Immunology, Immunology and Allergy, 610 Medicine & health
Abstract

BACKGROUND Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step. OBJECTIVE We explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance. METHODS Extensive flow-cytometric immune-phenotyping was performed. Rare variants of immune system genes were analyzed by whole exome sequencing. DNA repair functionality and T cell-intrinsic DNA damage tolerance was tested with an ensemble of in vitro and in silico tools. Antigen-receptor diversity and autoimmune features were characterized by high-throughput sequencing and autoantibody arrays. Reconstitution of wild-type vs. mutant LIG4 were performed in LIG4 knock-out Jurkat T cells and DNA damage tolerance was subsequently assessed. RESULTS A novel heterozygous LIG4 loss-of-function mutation (p.R580Q), associated with a dominantly inherited familial immune-dysregulation consisting of autoimmune cytopenias, and in the index patient with lymphoproliferation, agammaglobulinemia and adaptive immune cell infiltration into nonlymphoid organs. Immunophenotyping revealed reduced naïve CD4+ T cells and low TCR-Vα7.2+ T cells, while T/B-cell receptor repertoires showed only mild alterations. Cohort screening identified two other non-related patients with the monoallelic LIG4 mutation p.A842D recapitulating clinical and immune-phenotypic dysregulations observed in the index family and displaying T cell-intrinsic DNA damage intolerance. Reconstitution experiments and molecular dynamics simulations categorize both missense mutations as loss-of-function and haploinsufficient. CONCLUSION We provide evidence that certain monoallelic LIG4 mutations may cause human immune dysregulation via haploinsufficiency.

Published
2023
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4. A novel functional mast cell assay for the detection of allergies

Author

Lukas Jörg, Arthur Helbling, Daniel Bachmann, Johannes Schmid, Jean-Pierre Kinet, Noemi Zbären, Daniel Brigger, Thomas Kaufmann, Hans Jürgen Hoffmann, Alexander Eggel, and Michael P. Horn

Subjects
Allergy, immunotherapy monitoring, medicine.medical_treatment, Immunology, Cell, mast cells, 610 Medicine & health, Immunoglobulin E, diagnostic testing, Mice, 03 medical and health sciences, 0302 clinical medicine, Allergies, human high-affinity IgE receptor, Hypersensitivity, Animals, Humans, Immunology and Allergy, Medicine, Mast Cells, 030304 developmental biology, homeobox B8, 0303 health sciences, biology, Receptors, IgE, business.industry, Cellular Assay, Immunotherapy, Allergens, Mast cell, medicine.disease, 3. Good health, Tolerance induction, medicine.anatomical_structure, biology.protein, IgE, Bone marrow, business, functional assay, 030215 immunology
Abstract

Background Clinical management of allergic diseases has been hampered by the lack of safe and convenient tests to reliably identify culprit allergens and to closely follow changes in disease activity over time. Because allergy diagnosis is a complex and laborious multistep procedure, there is an urgent need for simpler but still functionally accurate ex vivo assays allowing objective diagnosis, substantiating treatment choices, and quantifying therapeutic responses. Objective In this study, we sought to develop a novel functional cell-based assay that relies on passive sensitization of allergic effector cells with patient serum, circumventing current limitations in allergy diagnosis. Methods We genetically engineered a conditional homeobox B8 (Hoxb8)-immortalized progenitor line from the bone marrow of mice that are transgenic for the human high-affinity IgE receptor (FceRIα). These cells can be reproducibly differentiated into mature Hoxb8 mast cells within 5 days of culture in virtually unlimited numbers. Results We demonstrate that the established Hoxb8 mast cell assay can be used to accurately measure total IgE levels, identify culprit allergens, longitudinally monitor allergen-specific immunotherapy, and potentially determine the time point of tolerance induction upon allergen-specific immunotherapy in patients with allergy. To facilitate the analysis of large testing volumes, we demonstrate a proof-of-concept for a high-throughput screening application based on fluorescent cell barcoding using the engineered Hoxb8 mast cells. Conclusions Our results indicate that this novel mast cell assay could represent a valuable tool to support clinicians in the identification of IgE-mediated allergies and in the quantification of treatment efficacy as well as duration of therapeutic response.

Published
2022
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5. Trained immunity and tolerance in innate lymphoid cells, monocytes, and dendritic cells during allergen-specific immunotherapy

Author

Marcin Moniuszko, Tadech Boonpiyathad, Helga Kahlert, Anna Gschwend, Hideaki Morita, Fiorella Ruchti, Urszula Radzikowska, Anna Głobińska, Cezmi A. Akdis, Christoph Willers, Milena Sokolowska, Arthur Helbling, Mübeccel Akdis, Andreas Nandy, Andrzej Eljaszewicz, Stefania Arasi, Nadine Berek, University of Zurich, and Sokolowska, Milena

Subjects
Adult, Male, 0301 basic medicine, Myeloid, Immunology, 610 Medicine & health, Plasmacytoid dendritic cell, Biology, Poaceae, Monocytes, Natural killer cell, Young Adult, 03 medical and health sciences, 0302 clinical medicine, 10183 Swiss Institute of Allergy and Asthma Research, Immune Tolerance, medicine, Humans, Immunology and Allergy, Lymphocytes, Antigen-presenting cell, Betula, 2403 Immunology, Innate immune system, Monocyte, Innate lymphoid cell, Rhinitis, Allergic, Seasonal, Dendritic Cells, Dendritic cell, Middle Aged, Immunity, Innate, 030104 developmental biology, medicine.anatomical_structure, Desensitization, Immunologic, 2723 Immunology and Allergy, Pollen, Female, 030215 immunology
Abstract

BACKGROUND Despite the efficacy of allergen-specific immunotherapy (AIT), the role of trained immunity and tolerance in this process has not been elucidated. OBJECTIVE Here, we have performed a comprehensive longitudinal analysis of the systemic innate immune cell repertoire during the course of AIT. METHODS Patients with allergy received standard preseasonal subcutaneous AIT with allergoids to birch and/or grass. Healthy controls were monitored without any intervention. Flow cytometry of innate lymphoid cell (ILC), natural killer cell, monocyte cell, and dendritic cell (DC) subsets was performed at baseline, 3 months (birch season), 6 months (grass seasons), and 12 months after the therapy in patients or at similar seasonal time points in controls. Additional analyses were performed in the third-year birch and grass season. RESULTS We observed a durable decrease in group 2 ILCs and an increase of group 1 ILCs after AIT, with dynamic changes in their composition. We found that an expansion of CD127+CD25++ clusters caused observed shifts in the heterogeneity of group 1 ILCs. In addition, we observed development of CD127+CD25++c-Kit+ group 3 ILC clusters. Moreover, we found an increase in the number of intermediate monocytes in parallel with a reduction in nonclassical monocytes during the first year after AIT. Classical and intermediate monocytes presented significant heterogeneity in patients with allergy, but AIT reduced the HLA-DR++ clusters. Finally, an increase in plasmacytoid DCs and CD141+ myeloid DCs was observed in individuals with allergy, whereas the number of CD1c+ myeloid DCs was reduced during the first year of AIT. CONCLUSION AIT induces changes in the composition and heterogeneity of circulating innate immune cells and brings them to the level observed in healthy individuals. Monitoring of ILCs, monocytes, and DCs during AIT might serve as a novel biomarker strategy.

Published
2021
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6. List of Contributors

Author

Roshini Sarah Abraham, Cristina Albanesi, Ilias Alevizos, Juan Anguita, Brendan Antiochos, Cynthia Aranow, John P. Atkinson, Howard A. Austin, Subash Babu, Mark C. Ballow, James E. Balow, John W. Belmont, Claudia Berek, Timothy Beukelman, Tapan Bhavsar, J. Andrew Bird, Sarah E. Blutt, Mark Boguniewicz, Rafael Bonamichi-Santos, Bertrand Boisson, Elena Borzova, Prosper N. Boyaka, Joshua Boyce, Sarah K. Browne, Wesley Burks, Jacinta Bustamante, Virginia L. Calder, Matthew Campbell, Adela Rambi G. Cardones, Jean-Laurent Casanova, Mariana Castells, Lisa A. Cavacini, Edwin S.L. Chan, David D. Chaplin, W. Winn Chatham, Edward S. Chen, Javier Chinen, Lisa Christopher-Stine, Michael Ciancanelli, Andrew P. Cope, David B. Corry, Filippo Crea, Randy Q. Cron, Jennifer M. Cuellar-Rodriguez, Marinos C. Dalakas, Sara M. Dann, Betty Diamond, Terry W. Du, Stéphanie Dupuis-Boisson, Todd N. Eagar, Craig A. Elmets, Doruk Erkan, Laura Fanning, Erol Fikrig, Davide Flego, Thomas A. Fleisher, Luz Fonacier, Andrew P. Fontenot, Alexandra F. Freeman, Anthony J. Frew, Kohtaro Fujihashi, Massimo Gadina, Moshe E. Gatt, M. Eric Gershwin, Susan L. Gillespie, Jörg J. Goronzy, Sangeeta Goswami, Clive E.H. Grattan, Neil S. Greenspan, Sarthak Gupta, Claire E. Gustafson, Russell P. Hall, Robert G. Hamilton, Laurie E. Harrington, Leonard C. Harrison, Sarfaraz A. Hasni, Arthur Helbling, Joanna Hester, Steven M. Holland, Dennis Hourcade, Nicholas D. Huntington, Tracy Hwangpo, John B. Imboden, Fadi Issa, Shai Izraeli, Elaine S. Jaffe, Sirpa Jalkanen, Stacie Jones, Emmanuelle Jouanguy, Sarah Kabbani, Stefan H.E. Kaufmann, Farrah Kheradmand, Donald B. Kohn, Robert Korngold, Anna Kovalszki, Douglas B. Kuhns, Hrishikesh Kulkarni, Caroline Y. Kuo, Arash Lahouti, C. Ola Landgren, Arian Laurence, Joyce S. Lee, Catherine Lemière, Donald Y.M. Leung, Arnold I. Levinson, Ofer Levy, Dorothy E. Lewis, Phoebe Lin, Andreas Linkermann, Giovanna Liuzzo, Michael D. Lockshin, Allison K. Lord, Jay N. Lozier, Amber Luong, Raashid Luqmani, Meggan Mackay, Jonathan S. Maltzman, Peter J. Mannon, Michael P. Manns, James G. Martin, Craig L. Maynard, Samual McCash, Douglas R. McDonald, Peter C. Melby, Stephen D. Miller, Anna L. Mitchell, Amirah Mohd-Zaki, Carolyn Mold, David R. Moller, Dimitrios S. Monos, Scott N. Mueller, Catharina M. Mulders-Manders, Mark J. Mulligan, Ulrich R. Müller, Pashna N. Munshi, Kazunori Murata, Philip M. Murphy, Nicolás Navasa, Pierre Noel, Luigi D. Notarangelo, Robert L. Nussbaum, Thomas B. Nutman, Stephen L. Nutt, João B. Oliveira, Thomas L. Ortel, John J. O'Shea, Sung-Yun Pai, Lavannya Pandit, Mary E. Paul, Simon H.S. Pearce, Daniela Pedicino, Erik J. Peterson, Capucine Picard, Stefania Pittaluga, Debra Long Priel, Jennifer Puck, Anne Puel, Andreas Radbruch, Stephen T. Reece, John D. Reveille, Robert R. Rich, Chaim M. Roifman, Antony Rosen, James T. Rosenbaum, Sergio D. Rosenzweig, Barry T. Rouse, Scott D. Rowley, Shimon Sakaguchi, Marko Salmi, Andrea J. Sant, Sarah W. Satola, Valerie Saw, Marcos C. Schechter, Harry W. Schroeder, Benjamin M. Segal, Carlo Selmi, Sushma Shankar, Anu Sharma, Padmanee Sharma, William T. Shearer, Richard M. Siegel, Anna Simon, Gideon P. Smith, David S. Stephens, Robin Stephens, Alex Straumann, Leyla Y. Teos, Laura Timares, Wulf Tonnus, Raul M. Torres, Gülbü Uzel, Jeroen C.H. van der Hilst, Jos W.M. van der Meer, John Varga, Jatin M. Vyas, Meryl Waldman, Peter Weiser, Peter F. Weller, Cornelia M. Weyand, Fredrick M. Wigley, Robert J. Winchester, James B. Wing, Kathryn J. Wood, Xiaobo Wu, Hui Xu, Cassian Yee, and Shen-Ying Zhang

Published
2019
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8. List of contributors

Author

Roshini Sarah Abraham, Cristina Albanesi, Ilias Alevizos, Juan Anguita, Gregory M. Anstead, Cynthia Aranow, Howard A. Austin, Subash Babu, Mark C. Ballow, James E. Balow, David R. Barnidge, John W. Belmont, Gabrielle T. Belz, Dina Ben-Yehuda, Claudia Berek, Timothy Beukelman, Thomas Bieber, Johannes W.J. Bijlsma, Jack J.H. Bleesing, Sarah E. Blutt, Barbara Bohle, Elena Borzova, Prosper N. Boyaka, Brockow Knut, Jacinta Bustamante, Frank Buttgereit, Mary Byrne, Virginia L. Calder, Magda Carneiro-Sampaio, Sebastian Carotta, Jean-Laurent Casanova, Lisa A. Cavacini, Edwin S.L. Chan, Javier Chinen, Tanuja Chitnis, Monique Cho, Lisa Christopher-Stine, Andrew P. Cope, David B. Corry, Tricia Cottrell, Antonio Coutinho, Marco Craveiro, Randy Q. Cron, Jennifer Cuellar-Rodriguez, Marinos C. Dalakas, Stephanie C. de Barros, Blythe H. Devlin, Betty Diamond, Angela Dispenzieri, Terry W. Du Clos, Stéphanie Dupuis-Boisson, Todd N. Eagar, Kim D. Edhegard, George S. Eisenbarth, Craig A. Elmets, Doruk Erkan, Mark B. Feinberg, Erol Fikrig, Thomas A. Fleisher, Andrew P. Fontenot, Luis M. Franco, Alexandra F. Freeman, Anthony J. Frew, Thea Friedman, Kohtaro Fujihashi, Massimo Gadina, Stephen J. Galli, H. Bobby Gaspar, Moshe E. Gatt, M. Eric Gershwin, Kamran Ghoreschi, Susan L. Gillespie, Jörg J. Goronzy, Clive E.H. Grattan, Neil S. Greenspan, Eyal Grunebaum, Gabrielle Haeberli, Russell P. Hall, Robert G. Hamilton, Gregory R. Harriman, Sarfaraz A. Hasni, Arthur Helbling, Melanie Hingorani, Steven M. Holland, Petr L. Hruz, Gabor Illei, John B. Imboden, Shai Izraeli, Elaine S. Jaffe, Caroline Jagobi, Sirpa Jalkanen, Pim Jetanalin, Emmanuelle Jouanguy, Carl H. June, Axel Kallies, Stefan H.E. Kaufmann, Arthur Kavanaugh, Sabiha Khan, Farrah Kheradmand, Samia J. Khoury, Gary A. Koretzky, Robert Korngold, Anna Kovalszki, Douglas B. Kuhns, Robert A. Kyle, Ian R. Lanza, Arian Laurence, Susan J. Lee, Michael J. Lenardo, Arnold I. Levinson, Ofer Levy, David B. Lewis, Dorothy E. Lewis, Sue L. Lightman, Michael D. Lockshin, Michael T. Lotze, Amber Luong, Meggan Mackay, Jean-Luc Malo, Jonathan S. Maltzman, Peter J. Mannon, Michael P. Manns, Mary Louise Markert, Elizabeth A. McCarthy, Douglas R. McDonald, Jerry R. McGhee, Peter C. Melby, Dean D. Metcalfe, Martin Metz, Stephen D. Miller, Anna L. Mitchell, Shruti Mittal, Makoto Miyara, Carolyn Mold, David R. Moller, Scott N. Mueller, Ulrich R. Müller, Philip M. Murphy, Pierre Noel, Luigi Notarangelo, Thomas B. Nutman, Stephen L. Nutt, João B. Oliveira, Chris M. Olson, John J. O'Shea, Sung-Yun Pai, Lavannya Pandit, Mary E. Paul, Simon H.S. Pearce, Erik J. Peterson, Capucine Picard, Werner J. Pichler, Stefania Pittaluga, Anne Puel, Andreas Radbruch, Stephen T. Reece, John D. Reveille, Robert R. Rich, Christine Rivat, Bruce W.S. Robinson, John R. Rodgers, Chaim M. Roifman, Antony Rosen, James T. Rosenbaum, Barry T. Rouse, Scott D. Rowley, Shimon Sakaguchi, Marko Salmi, Harry W. Schroeder, Markus J.H. Seibel, Carlo Selmi, William M. Shafer, Prediman K. Shah, Sushma Shankar, Alan R. Shaw, William T. Shearer, Javed Sheikh, Richard Siegel, Anna Simon, Philip L. Simonian, Gideon P. Smith, Justine R. Smith, Andrew L. Snow, David S. Stephens, John H. Stone, Alex Straumann, Helen C. Su, Louise Swainson, Ewa Szymanska-Mroczek, Naomi Taylor, Adrian J. Thrasher, Laura Timares, Raul M. Torres, Gülbŭ Uzel, Jos W.M. van der Meer, Jeroen C.H. van der Hilst, John Varga, Meryl Waldman, Peter Weiser, Peter F. Weller, Cornelia M. Weyand, Theresa L. Whiteside, Fredrick M. Wigley, Robert J. Winchester, Kajsa Wing, Kathryn Wood, Hui Xu, Shen-Ying Zhang, and Valérie S. Zimmermann

Published
2013
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9. Contributors

Author

Shizuo Akira, Juan Anguita, Gregory M. Anstead, Cynthia Aranow, Howard A. Austin, Subash Babu, James R. Baker, Christopher S. Baliga, Mark Ballow, James E. Balow, Emil J. Bardana, Matthias D. Becker, John W. Belmont, Dina Ben-Yehuda, Claudia Berek, Thomas Bieber, Johannes W.J. Bijlsma, Jack J.H. Bleesing, Sarah E. Blutt, Elena Borzova, Prosper N. Boyaka, Knut Brockow, Ralph C. Budd, Frank Buttgereit, Virginia L. Calder, Fabio Candotti, Sebastian Carotta, Jean-Laurent Casanova, Marilia Cascalho, Edwin S.L. Chan, Javier Chinen, Monique E. Cho, Lisa Christopher-Stine, Helen L. Collins, Andrew P. Cope, Irene Cortese, Bruce N. Cronstein, Adnan Custovic, Marinos C. Dalakas, Blythe H. Devlin, Betty Diamond, Angela Dispenzieri, Joost P.H. Drenth, Terry W. Du Clos, Mark S. Dykewicz, Todd N. Eagar, George S. Eisenbarth, Charles O. Elson, Doruk Erkan, Mark Feinberg, Erol Fikrig, Alain Fischer, Thomas A. Fleisher, Andrew P. Fontenot, Karen A. Fortner, Anthony J. Frew, Thea M. Friedman, Kohtaro Fujihashi, Stephen J. Galli, Moshe E. Gatt, M. Eric Gershwin, Jörg J. Goronzy, Clive E.H. Grattan, Neil S. Greenspan, Beatrix Grubeck-Loebenstein, Gabrielle Haeberli, Russell P. Hall, Robert G. Hamilton, Gregory R. Harriman, Khaled M. Hassan, Arthur Helbling, David B. Hellmann, Vivian Hernandez-Trujillo, Melanie Hingorani, Steven M. Holland, Henry A. Homburger, McDonald Horne, Gabor Illei, John Imboden, Ken J. Ishii, Shai Izraeli, Elaine S. Jaffe, Sirpa Jalkanen, Carl H. June, Barry D. Kahan, Axel Kallies, Stefan H.E. Kaufmann, Arthur F. Kavanaugh, Gary Koretzky, Robert Korngold, Rania D. Kovaiou, Douglas B. Kuhns, Roger Kurlander, Robert A. Kyle, H. Clifford Lane, Arian Laurence, Françoise Le Deist, Susan J. Lee, Steven J. Lemery, Michael J. Lenardo, Arnold I. Levinson, David B. Lewis, Dorothy E. Lewis, Jay Lieberman, Phil Lieberman, Sue L. Lightman, Michael D. Lockshin, Michael T. Lotze, Meggan Mackay, Jonathan S. Maltzman, Michael P. Manns, Markus Y. Mapara, Susana Marinho, M. Louise Markert, Alberto Martini, Seth L. Masters, Evelina Mazzolari, Henry F. McFarland, Jerry R. McGhee, Frank McKenna, Peter C. Melby, Dean D. Metcalfe, Martin Metz, Joann M. Mican, Stephen D. Miller, Carolyn Mold, David R. Moller, Anthony Montanaro, Scott N. Mueller, Ulrich R. Müller, Philip M. Murphy, Pierre Noel, Luigi D. Notarangelo, Thomas B. Nutman, Stephen L. Nutt, João Bosco de Oliveira, Stephen N. Oliver, Chris M. Olson, John O'shea, Mary E. Paul, Erik J. Peterson, Capucine Picard, Werner J. Pichler, Stanley R. Pillemer, Stefania Pittaluga, Jeffrey L. Platt, Paul H. Plotz, Andreas Radbruch, Angelo Ravelli, John D. Reveille, Robert R. Rich, Margaret E. Rick, Kimberly A. Risma, John R. Rodgers, Antony Rosen, James T. Rosenbaum, Marc E. Rothenberg, Barry T. Rouse, Scott Rowley, Martina Rudelius, Shimon Sakaguchi, Marko Salmi, Ulrich E. Schaible, Harry W. Schroeder, Marvin I. Schwarz, Markus J.H. Seibel, Carlo Selmi, William M. Shafer, Prediman K. Shah, Maryam Shahbaz-Samavi, Alan R. Shaw, William T. Shearer, Scott H. Sicherer, Richard Siegel, Ravinder Jit Singh, Justine R. Smith, Phillip D. Smith, Michael C. Sneller, John W. Steinke, David S. Stephens, John H. Stone, Helen C. Su, Cristina M. Tato, Raul M. Torres, Gülbû Uzel, Jeroen C.H. van der Hilst, Jos W.M. van der Meer, John Varga, José A. Villadangos, Su He Wang, Birgit Weinberger, Peter F. Weller, Cornelia M. Weyand, Fredrick M. Wigley, Robert J. Winchester, Kajsa Wing, Louise J. Young, and Li Zuo

Published
2008
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10. Allergic reactions to stinging and biting insects

Author

Ulrich R. Müller, Arthur Helbling, and Gabrielle Haeberli

Subjects
Allergy, biology, media_common.quotation_subject, fungi, Hymenoptera venom allergy, Specific immunotherapy, Venom, Insect, Hymenoptera, biology.organism_classification, medicine.disease, complex mixtures, Biting, Immunology, medicine, Effective treatment, media_common
Abstract

Encounters with insects are often accidental, but not unusual, and occur relatively frequently. Allergy to Hymenoptera venom is one of the most important causes of allergic and anaphylactic reactions. Even though more than 100,000 Hymenoptera species are known, honeybee and wasp stings are the most prevalent elicitors of Hymenoptera venom allergy worldwide. Of the identified honeybee and wasp venom allergens, the nonglycosylated, species-specific major allergens Api m1 and Api m10 (honeybee), Ves v 5 and Ves v 1 (wasp), as well as few analogous venoms of other species are commercially available for diagnostic in-vitro-tests. In case of double positivity of specific serum IgE to both whole venoms these allergens and other in vitro assays may be helpful for the selection of the causative venom for specific immunotherapy. Specific immunotherapy over 3 to 5 years with insect venoms containing the important allergens is still the only causal and effective treatment of Hymenoptera venom allergy.

Published
2008
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