236 results on '"Reto Crameri"'
Search Results
2. IgE Sensitization Profiles Differ between Adult Patients with Severe and Moderate Atopic Dermatitis.
- Author
-
Irene Mittermann, Gustav Wikberg, Catharina Johansson, Christian Lupinek, Lena Lundeberg, Reto Crameri, Rudolf Valenta, and Annika Scheynius
- Subjects
Medicine ,Science - Abstract
BackgroundAtopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors.AimTo characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens.MethodologyAdult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins.ResultsIgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD.ConclusionWe have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD.
- Published
- 2016
- Full Text
- View/download PDF
3. Phage Display Based Cloning of Proteins Interacting with the Cytoplasmic Tail of Membrane Immunoglobulins
- Author
-
Roland Geisberger, Martin Prlic, Gertrude Achatz-Straussberger, Iris Oberndorfer, Elke Luger, Marinus Lamers, Reto Crameri, Ulrich Appenzeller, Jürgen Wienands, Michael Breitenbach, Fatima Ferreira, and Gernot Achatz
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2002
- Full Text
- View/download PDF
4. High-throughput isolation of recombinant antibodies against recombinant allergens
- Author
-
Claudio Rhyner, Zoltan Konthur, Kurt Blaser, and Reto Crameri
- Subjects
Biology (General) ,QH301-705.5 - Published
- 2003
- Full Text
- View/download PDF
5. Correction: In Vitro Evolution of Allergy Vaccine Candidates, with Maintained Structure, but Reduced B Cell and T Cell Activation Capacity.
- Author
-
Ola B. Nilsson, Justus Adedoyin, Claudio Rhyner, Theresa Neimert-Andersson, Jeanette Grundström, Kurt D. Berndt, Reto Crameri, and Hans Grönlund
- Subjects
Medicine ,Science - Published
- 2012
- Full Text
- View/download PDF
6. In vitro evolution of allergy vaccine candidates, with maintained structure, but reduced B cell and T cell activation capacity.
- Author
-
Ola B Nilsson, Justus Adedoyin, Claudio Rhyner, Theresa Neimert-Andersson, Jeanette Grundström, Kurt D Berndt, Reto Crameri, and Hans Grönlund
- Subjects
Medicine ,Science - Abstract
Allergy and asthma to cat (Felis domesticus) affects about 10% of the population in affluent countries. Immediate allergic symptoms are primarily mediated via IgE antibodies binding to B cell epitopes, whereas late phase inflammatory reactions are mediated via activated T cell recognition of allergen-specific T cell epitopes. Allergen-specific immunotherapy relieves symptoms and is the only treatment inducing a long-lasting protection by induction of protective immune responses. The aim of this study was to produce an allergy vaccine designed with the combined features of attenuated T cell activation, reduced anaphylactic properties, retained molecular integrity and induction of efficient IgE blocking IgG antibodies for safer and efficacious treatment of patients with allergy and asthma to cat. The template gene coding for rFel d 1 was used to introduce random mutations, which was subsequently expressed in large phage libraries. Despite accumulated mutations by up to 7 rounds of iterative error-prone PCR and biopanning, surface topology and structure was essentially maintained using IgE-antibodies from cat allergic patients for phage enrichment. Four candidates were isolated, displaying similar or lower IgE binding, reduced anaphylactic activity as measured by their capacity to induce basophil degranulation and, importantly, a significantly lower T cell reactivity in lymphoproliferative assays compared to the original rFel d 1. In addition, all mutants showed ability to induce blocking antibodies in immunized mice.The approach presented here provides a straightforward procedure to generate a novel type of allergy vaccines for safer and efficacious treatment of allergic patients.
- Published
- 2011
- Full Text
- View/download PDF
7. GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells.
- Author
-
Pierre-Yves Mantel, Harmjan Kuipers, Onur Boyman, Claudio Rhyner, Nadia Ouaked, Beate Rückert, Christian Karagiannidis, Bart N Lambrecht, Rudolf W Hendriks, Reto Crameri, Cezmi A Akdis, Kurt Blaser, and Carsten B Schmidt-Weber
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-beta-mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.
- Published
- 2007
- Full Text
- View/download PDF
8. Fungal allergy and pathogenicity
- Author
-
Michael BREITENBACH, Reto CRAMERI, and Samuel B. LEHRER
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Published
- 2002
- Full Text
- View/download PDF
9. Structural aspects of fungal allergens
- Author
-
Reto Crameri, University of Zurich, and Crameri, Reto
- Subjects
Models, Molecular ,2403 Immunology ,Antigens, Fungal ,Molecular Structure ,business.industry ,Intracellular protein ,Immunology ,Fungi ,610 Medicine & health ,Allergens ,Cross Reactions ,Biology ,3. Good health ,Biotechnology ,Biochemistry ,10183 Swiss Institute of Allergy and Asthma Research ,Hypersensitivity ,2723 Immunology and Allergy ,Humans ,Immunology and Allergy ,business - Abstract
Despite the increasing number of solved crystal structures of allergens, the key question why some proteins are allergenic and the vast majority is not remains unanswered. The situation is not different for fungal allergens which cover a wide variety of proteins with different chemical properties and biological functions. They cover enzymes, cell wall, secreted, and intracellular proteins which, except cross-reactive allergens, does not show any evidence for structural similarities at least at the three-dimensional level. However, from a diagnostic point of view, pure allergens biotechnologically produced by recombinant technology can provide us, in contrast to fungal extracts which are hardly producible as standardized reagents, with highly pure perfectly standardized diagnostic reagents.
- Published
- 2021
10. Molecular allergen profiling in horses by microarray reveals Fag e 2 from buckwheat as a frequent sensitizer
- Author
-
Claudio Rhyner, Annika Scheynius, Yvonne Resch-Marat, Lukas Einhorn, Hiroshi Matsuda, Gerlinde Hofstetter, Edmund K. Hainisch, Irene Mittermann, Isabella Pali-Schöll, Eliane Isabelle Marti, Susanne Vrtala, Reto Crameri, H Sato, I Fukuda, Akane Tanaka, Rie Satoh, Sabine Brandt, Kanichi Kusano, Reiko Teshima, Rudolf Valenta, Erika Jensen-Jarolim, University of Zurich, and Jensen-Jarolim, E
- Subjects
Male ,0301 basic medicine ,Allergy ,Microarray ,Immunology ,610 Medicine & health ,component‐resolved diagnosis ,Immunoglobulin E ,medicine.disease_cause ,Allergic sensitization ,Epitopes ,03 medical and health sciences ,Allergen ,10183 Swiss Institute of Allergy and Asthma Research ,medicine ,Animals ,Humans ,Immunology and Allergy ,Horses ,molecular ,Sensitization ,Recurrent airway obstruction ,2403 Immunology ,ISAC ,biology ,business.industry ,Horse ,Allergens ,Antigens, Plant ,medicine.disease ,horse ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Experimental Allergy and Immunology ,2723 Immunology and Allergy ,biology.protein ,Female ,Original Article ,IgE ,ORIGINAL ARTICLES ,business ,microarray ,Epitope Mapping ,Fagopyrum ,allergen - Abstract
BACKGROUND Companion animals are also affected by IgE-mediated allergies, but the eliciting molecules are largely unknown. We aimed at refining an allergen microarray to explore sensitization in horses and compare it to the human IgE reactivity profiles. METHODS Custom-designed allergen microarray was produced on the basis of the ImmunoCAP ISAC technology containing 131 allergens. Sera from 51 horses derived from Europe or Japan were tested for specific IgE reactivity. The included horse patients were diagnosed for eczema due to insect bite hypersensitivity, chronic coughing, recurrent airway obstruction and urticaria or were clinically asymptomatic. RESULTS Horses showed individual IgE-binding patterns irrespective of their health status, indicating sensitization. In contrast to European and Japanese human sensitization patterns, frequently recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass, likely due to specific respiratory exposure around paddocks and near the ground. The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S-albumin Fag e 2 from buckwheat, which recently gained importance not only in human but also in horse diet. CONCLUSION In line with the One Health concept, covering human health, animal health and environmental health, allergen microarrays provide novel information on the allergen sensitization patterns of the companion animals around us, which may form a basis for allergen-specific preventive and therapeutic concepts.
- Published
- 2018
11. Structural aspects and clinical relevance of Aspergillus fumigatus antigens/allergens
- Author
-
Reto Crameri, Andreas G. Glaser, Sabine Zeller, Michael Weichel, Andreas Limacher, and Claudio Rhyner
- Subjects
biology ,cDNA library ,General Medicine ,biology.organism_classification ,Immunoglobulin E ,medicine.disease ,Epitope ,Aspergillus fumigatus ,Microbiology ,Infectious Diseases ,Antigen ,Ribosomal protein ,biology.protein ,medicine ,Antibody ,Allergic bronchopulmonary aspergillosis - Abstract
Robotics-based high throughput screening of Aspergillus fumigatus cDNA libraries displayed on phage surfaces revealed at last 81 different structures able to bind IgE from serum of patients sensitized to this fungus. Among these, species-specific as well as phylogenetically highly conserved structures and such with unknown function have been detected. A subset of cDNAs have been used to produce and characterize the corresponding recombinant allergens which have proven to be useful diagnostic reagents allowing specific detection of A. fumigatus sensitization and differential diagnosis of allergic bronchopulmonary aspergillosis. Phylogenetically highly conserved structures like manganese-dependent superoxide dismutase, P2 acidic ribosomal protein, cyclophilins and thioredoxins induce, beyond sensitization, IgE antibodies able to cross-react with the corresponding homologous self antigens. These reactions, likely to contribute to the exacerbation and perpetuation of allergic bronchopulmonary aspergillosis, can be traced back to shared conformational B-cell epitopes build up from conserved amino acid residues scattered over the surface of the molecules as shown by detailed analyses of the crystal structures.
- Published
- 2018
12. Evanescence wave-based technology for the rapid and sensitive quantification of biological analytes
- Author
-
Torsten Zuberbier, Reto Crameri, Gerald Quapil, Max Wiki, Claudio Rhyner, Manfred Schawaller, Cezmi A. Akdis, and University of Zurich
- Subjects
Analyte ,2403 Immunology ,Chromatography ,business.industry ,Immunology ,Enzyme-Linked Immunosorbent Assay ,610 Medicine & health ,Biosensing Techniques ,030204 cardiovascular system & hematology ,Molecular biology ,03 medical and health sciences ,0302 clinical medicine ,030202 anesthesiology ,10183 Swiss Institute of Allergy and Asthma Research ,2723 Immunology and Allergy ,Humans ,Immunology and Allergy ,Medicine ,business - Published
- 2018
13. Aspergillus fumigatus-specific immunoglobulin levels in BALF of CF patients
- Author
-
Zsolt Szépfalusi, Petra Fucik, Birgit Pfaller, Sabine Renner, Markus Debiasi, Klara Schmidthaler, Jonathan Argeny, Thomas Eiwegger, Saskia Gruber, Claudio Rhyner, Mia Goña-Höpler, Andreas G. Glaser, Reto Crameri, Edith Nachbaur, Stefan Kanolzer, and University of Zurich
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Immunoglobulin levels ,biology ,business.industry ,lcsh:R ,Original Research Letter ,lcsh:Medicine ,610 Medicine & health ,respiratory system ,biology.organism_classification ,3. Good health ,Aspergillus fumigatus ,Microbiology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030228 respiratory system ,10183 Swiss Institute of Allergy and Asthma Research ,otorhinolaryngologic diseases ,Medicine ,business - Abstract
A lack of correlation between systemic and local IgE production at mucosal sites has been reported for allergic asthma [1–5], allergic rhinitis [6, 7] and chronic rhinosinusitis with nasal polyps [8–10]. In allergic asthmatics, local IgE production is higher than in nonallergic asthmatics [3] and high local IgE levels have been linked to the clinical phenotype. Interestingly, in cases of nasal polyps, local IgE targets mainly superantigens [8]., IgE responses to Aspergillus fumigatus in cystic fibrosis lungs http://ow.ly/XXwv30furqs
- Published
- 2017
14. Laser-Assisted Intradermal Delivery of Adjuvant-Free Vaccines Targeting XCR1+ Dendritic Cells Induces Potent Antitumoral Responses
- Author
-
Bjarne Bogen, Dorothea Terhorst, Reto Crameri, Sandrine Henri, Elmira Lechat, Camille Malosse, Reinhard Braun, Samira Tamoutounour, Bernard Malissen, Anna Baranska, Even Fossum, and Mattia Garbani
- Subjects
Chemokine ,XCR1 ,Injections, Intradermal ,Ovalbumin ,medicine.medical_treatment ,T cell ,Immunology ,Melanoma, Experimental ,Cancer Vaccines ,Mice ,T-Lymphocyte Subsets ,Neoplasms ,medicine ,Animals ,Immunology and Allergy ,Mice, Knockout ,biology ,business.industry ,Melanoma ,Dendritic Cells ,Immunotherapy ,medicine.disease ,Chemokines, C ,Tumor Burden ,Adaptor Proteins, Vesicular Transport ,Disease Models, Animal ,medicine.anatomical_structure ,Myeloid Differentiation Factor 88 ,biology.protein ,Receptors, Chemokine ,business ,Adjuvant ,CD8 ,Protein Binding ,XCL1 - Abstract
The development of vaccines inducing efficient CD8+ T cell responses is the focus of intense research. Dendritic cells (DCs) expressing the XCR1 chemokine receptor, also known as CD103+ or CD8α+ DCs, excel in the presentation of extracellular Ags to CD8+ T cells. Because of its high numbers of DCs, including XCR1+ DCs, the skin dermis is an attractive site for vaccine administration. By creating laser-generated micropores through the epidermis, we targeted a model protein Ag fused to XCL1, the ligand of XCR1, to dermal XCR1+ DCs and induced Ag-specific CD8+ and CD4+ T cell responses. Efficient immunization required the emigration of XCR1+ dermal DCs to draining lymph nodes and occurred irrespective of TLR signaling. Moreover, a single intradermal immunization protected mice against melanoma tumor growth in prophylactic and therapeutic settings, in the absence of exogenous adjuvant. The mild inflammatory milieu created in the dermis by skin laser microporation itself most likely favored the development of potent T cell responses in the absence of exogenous adjuvants. The existence of functionally equivalent XCR1+ dermal DCs in humans should permit the translation of laser-assisted intradermal delivery of a tumor-specific vaccine targeting XCR1+ DCs to human cancer immunotherapy. Moreover, considering that the use of adjuvants in vaccines is often associated with safety issues, the possibility of inducing protective responses against melanoma tumor growth independently of the administration of exogenous adjuvants should facilitate the development of safer vaccines.
- Published
- 2015
15. Fungi: the neglected allergenic sources
- Author
-
Claudio Rhyner, Mattia Garbani, Reto Crameri, C. Huitema, University of Zurich, and Crameri, R
- Subjects
2403 Immunology ,Allergy ,education.field_of_study ,Antigens, Fungal ,Molecular Sequence Data ,Immunology ,Population ,Fungi ,610 Medicine & health ,Atopic dermatitis ,Biology ,medicine.disease ,3. Good health ,Clinical Practice ,10183 Swiss Institute of Allergy and Asthma Research ,Basic research ,2723 Immunology and Allergy ,Hypersensitivity ,medicine ,Humans ,Immunology and Allergy ,education ,Type I hypersensitivity ,Asthma - Abstract
Allergic diseases are considered the epidemics of the twentieth century estimated to affect more than 30% of the population in industrialized countries with a still increasing incidence. During the past two decades, the application of molecular biology allowed cloning, production and characterization of hundreds of recombinant allergens. In turn, knowledge about molecular, chemical and biologically relevant allergens contributed to increase our understanding of the mechanisms underlying IgE-mediated type I hypersensitivity reactions. It has been largely demonstrated that fungi are potent sources of allergenic molecules covering a vast variety of molecular structures including enzymes, toxins, cell wall components and phylogenetically highly conserved cross-reactive proteins. Despite the large knowledge accumulated and the compelling evidence for an involvement of fungal allergens in the pathophysiology of allergic diseases, fungi as a prominent source of allergens are still largely neglected in basic research as well as in clinical practice. This review aims to highlight the impact of fungal allergens with focus on asthma and atopic dermatitis.
- Published
- 2014
- Full Text
- View/download PDF
16. The contribution of biotechnology toward progress in diagnosis, management, and treatment of allergic diseases
- Author
-
Oscar Palomares, Reto Crameri, Claudio Rhyner, University of Zurich, and Palomares, O
- Subjects
2. Zero hunger ,2403 Immunology ,Vaccines ,Life span ,business.industry ,Life style ,Immunology ,Disease Management ,610 Medicine & health ,Immunologic Tests ,3. Good health ,Biotechnology ,Industrialisation ,10183 Swiss Institute of Allergy and Asthma Research ,Diagnosis management ,2723 Immunology and Allergy ,Hypersensitivity ,Immunology and Allergy ,Medicine ,Humans ,Decipherment ,Immunotherapy ,business - Abstract
'Biotechnology' has been intuitively used by humans since thousands of years for the production of foods, beverages, and drugs based on the experience without any scientific background. However, the golden era of this discipline emerged only during the second half of the last century. Incredible progresses have been achieved on all fields starting from the industrialization of the production of foods to the discovery of antibiotics, the decipherment of the genetic code, and rational approaches to understand and define the status we now call 'healthy'. The extremely complex interactions between genetic background, life style, and environmental factors influencing our continuously increasing life span have become more and more evident and steadily generate new questions which are only partly answered. Here, we try to summarize the contribution of biotechnology to our understanding, control, and cure of IgE-mediated allergic diseases. We are aware that a review of such a vast topic can never cover all aspects of the progress achieved in the different fields.
- Published
- 2014
17. Global allergy forum and second davos declaration 2013 allergy: Barriers to cure - Challenges and actions to be taken
- Author
-
Antonella Muraro, Thomas Bieber, R. Lauener, Knut Brockow, Ulf Darsow, Patrick G. Holt, Judah A. Denburg, Ulrike Müller, C Braun-Fahrländer, Reto Crameri, K. Blaser, Cezmi A. Akdis, Peter Schmid-Grendelmeier, Stephen J. Galli, Claudia Traidl-Hoffmann, Claudio Rhyner, Lanny J. Rosenwasser, Carsten B. Schmidt-Weber, Hans-Uwe Simon, Thomas A.E. Platts-Mills, Georg Schäppi, Remo Frei, Donald Y.M. Leung, Ruby Pawankar, John Bienenstock, Tilo Biedermann, J. Ring, Heidrun Behrendt, Liam O'Mahony, W. Ammann, M. van Hage, Mübeccel Akdis, R. van Ree, H. Koren, J. Gutermuth, Jeroen Buters, Werner Schmutz, Mikhail Sofiev, Kilian Eyerich, Markus Ollert, Dagmar Simon, University of Zurich, Specialities, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, and Experimental Immunology
- Subjects
medicine.medical_specialty ,Allergy ,2403 Immunology ,business.industry ,Immunology ,Declaration ,Alternative medicine ,10177 Dermatology Clinic ,610 Medicine & health ,asthma ,medicine.disease ,Europe ,10036 Medical Clinic ,10183 Swiss Institute of Allergy and Asthma Research ,Family medicine ,Dermatology clinic ,medicine ,2723 Immunology and Allergy ,Immunology and Allergy ,ddc:610 ,business - Published
- 2014
- Full Text
- View/download PDF
18. Histamine and gut mucosal immune regulation
- Author
-
Reto Crameri, Marek Jutel, Sylwia Smolinska, Liam O'Mahony, University of Zurich, and O'Mahony, L
- Subjects
Allergy ,Immunology ,610 Medicine & health ,Inflammation ,Biology ,Scombroid food poisoning ,Immunomodulation ,Histamine receptor ,chemistry.chemical_compound ,10183 Swiss Institute of Allergy and Asthma Research ,Food allergy ,medicine ,Animals ,Humans ,Immunology and Allergy ,Histamine H4 receptor ,Immunity, Mucosal ,2403 Immunology ,Mucous Membrane ,medicine.disease ,3. Good health ,Gastrointestinal Tract ,Mucosal immunology ,chemistry ,2723 Immunology and Allergy ,medicine.symptom ,Histamine - Abstract
Histamine is a biogenic amine with extensive effects on many cell types, mediated by the activation of its four receptors (H1R-H4R). Distinct effects are dependent on receptor subtypes and their differential expression. Within the gastrointestinal tract, histamine is present at relatively high concentrations, particularly during inflammatory responses. In this review, we discuss the immunoregulatory influence of histamine on a number of gastrointestinal disorders, including food allergy, scombroid food poisoning, histamine intolerance, irritable bowel syndrome, and inflammatory bowel disease. It is clear that the effects of histamine on mucosal immune homeostasis are dependent on expression and activity of the four currently known histamine receptors; however, the relative protective or pathogenic effects of histamine on inflammatory processes within the gut are still poorly defined and require further investigation.
- Published
- 2014
- Full Text
- View/download PDF
19. Mechanisms of peripheral tolerance to allergens
- Author
-
J. Ring, R. Lauener, Heidrun Behrendt, Reto Crameri, Cezmi A. Akdis, Mübeccel Akdis, Ozge Soyer, University of Zurich, and Akdis, C A
- Subjects
medicine.medical_treatment ,Immunology ,610 Medicine & health ,Inflammation ,Biology ,Immunoglobulin E ,Sensitivity and Specificity ,T-Lymphocytes, Regulatory ,Immune tolerance ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,10183 Swiss Institute of Allergy and Asthma Research ,Hypersensitivity ,Immune Tolerance ,medicine ,Humans ,Immunology and Allergy ,IL-2 receptor ,030304 developmental biology ,2403 Immunology ,B-Lymphocytes, Regulatory ,0303 health sciences ,Peripheral Tolerance ,Peripheral tolerance ,Dendritic Cells ,Immunotherapy ,Allergens ,Acquired immune system ,Interleukin-10 ,3. Good health ,Desensitization, Immunologic ,Immunoglobulin G ,Allergy ,T Helper Cells ,T Regulatory Cells ,Antibody Formation ,2723 Immunology and Allergy ,biology.protein ,Cytokines ,Th17 Cells ,medicine.symptom ,030215 immunology - Abstract
The immune system is regulated to protect the host from exaggerated stimulatory signals establishing a state of tolerance in healthy individuals. The disequilibrium in immune regulatory vs effector mechanisms results in allergic or autoimmune disorders in genetically predisposed subjects under certain environmental conditions. As demonstrated in allergen-specific immunotherapy and in the healthy immune response to high-dose allergen exposure models in humans, T regulatory cells are essential in the suppression of Th2-mediated inflammation, maintenance of immune tolerance, induction of the two suppressive cytokines interleukin-10 and transforming growth factor-beta, inhibition of allergen-specific IgE, and enhancement of IgG4 and IgA. Also, suppression of dendritic cells, mast cells, and eosinophils contributes to the construction of peripheral tolerance to allergens. This review focuses on mechanisms of peripheral tolerance to allergens with special emphasis on recent developments in the area of immune regulation.
- Published
- 2013
20. Artificial human sera: a breakthrough?
- Author
-
Reto Crameri, University of Zurich, and Crameri, R
- Subjects
0301 basic medicine ,2403 Immunology ,business.industry ,Immunology ,610 Medicine & health ,Computational biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Text mining ,030228 respiratory system ,10183 Swiss Institute of Allergy and Asthma Research ,2723 Immunology and Allergy ,Immunology and Allergy ,Medicine ,business - Published
- 2016
21. EAACI Molecular Allergology User's Guide
- Author
-
Jörg Kleine-Tebbe, Sandip D. Kamath, Karin Hoffmann-Sommergruber, Simon Blank, Kirsten Beyer, M. Ebisawa, Daniela Posa, Thomas A.E. Platts-Mills, Joaquín Sastre, Mika J. Mäkelä, Elide A. Pastorello, Philippe Eigenmann, Nikolaos G. Papadopoulos, Peter Schmid-Grendelmeier, Richard W. Weber, Fatima Ferreira, Luis Caraballo, Helen A. Brough, Edward F. Knol, J-C Caubet, Andreas L. Lopata, Annette Kuehn, Ioana Agache, Tilo Biedermann, Martine Morisset, Stefan Vieths, Antonella Muraro, Barbara Bohle, Johannes Schmid, Barbara Ballmer-Weber, Verena Niederberger, Stephanie Hofmaier, R. van Ree, Peter Korošec, Heimo Breiteneder, Magnus Wickman, Gideon Lack, Thilo Jakob, Martin Glatz, Rudolf Valenta, Lars K. Poulsen, Philipp P. Bosshard, Anna Nowak-Wegrzyn, Gabrielle Pauli, Rob C. Aalberse, Thomas Hawranek, Marek Jutel, Gabriele Gadermaier, Hans Jürgen Hoffmann, Uta Jappe, Nikolaos Douladiris, M. van Hage, Reto Crameri, P W Hellings, Enrico Scala, Janet M. Davies, Riccardo Asero, Domingo Barber, Monika Raulf, Markus Ollert, Christiane Hilger, Robert G. Hamilton, M. B. Bilò, Montserrat Fernandez-Rivas, Paolo Maria Matricardi, Landsteiner Laboratory, Ear, Nose and Throat, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Experimental Immunology, Caubet, Jean-Christoph Roger J-P, and Eigenmann, Philippe
- Subjects
0301 basic medicine ,Hypersensitivity, Immediate ,Allergy ,component-resolved diagnosis ,diagnosis ,Basophil ,medicine.disease_cause ,Immunoglobulin E ,Pediatrics ,profilins ,0302 clinical medicine ,Allergen ,Medicine ,Immunology and Allergy ,guidelines ,parvalbumins ,ddc:618 ,panallergens ,polcalcins ,biology ,atopic dermatitis ,food and beverages ,Perinatology ,3. Good health ,and Child Health ,medicine.anatomical_structure ,IgE ,lipocalins ,microarray ,Anaphylaxis ,Dander ,molecular allergology ,precision medicine ,Immunology ,Immunologic Tests ,tropomyosins ,03 medical and health sciences ,Food allergy ,diagnostic algorithms ,anaphylaxis ,Journal Article ,Humans ,Pediatrics, Perinatology, and Child Health ,House dust mite ,food allergy ,business.industry ,Allergens ,asthma ,biology.organism_classification ,medicine.disease ,allergy ,pathogenesis-related protein family 10 ,allergy diagnosis ,030104 developmental biology ,030228 respiratory system ,IgE cross-reactivity ,Pediatrics, Perinatology and Child Health ,biology.protein ,non-specific lipid transfer proteins ,serum albumins ,business ,Biomarkers - Abstract
The availability of allergen molecules ('components') from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled 'component-resolved diagnosis' (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.
- Published
- 2016
22. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor b, and TNF-a : Receptors, functions, and roles in diseases
- Author
-
Anna Głobińska, Cezmi A. Akdis, Terufumi Kubo, Paulina Wawrzyniak, Can Altunbulakli, Judith Olzhausen, Reto Crameri, Arturo Rinaldi, Andrzej Eljaszewicz, Zsolt István Komlósi, Umut Can Kucuksezer, Angela Treis, Barbara Stanic, Marcin Wawrzyniak, Thomas Eiwegger, Moira Prati, Claudio Rhyner, Ana Rebane, Marija Pezer, Milena Sokolowska, Oliver F. Wirz, Remo Frei, Mübeccel Akdis, Alar Aab, Su Duan, Kursat A Azkur, Liam O'Mahony, Carly Huitema, Ruth Ferstl, Kerstin Wanke, Patricia Konieczna, Kazunari Sugita, Rita Costa, Lena Hess, Josefina Zakzuk, Hideaki Morita, Nóra Kovács, Mattia Garbani, Norbert Meyer, and Willem van de Veen
- Subjects
0301 basic medicine ,Immunology ,Biology ,T-Lymphocytes, Regulatory ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Transforming Growth Factor beta ,Immunology and Allergy ,Animals ,Humans ,Receptor ,Toll-like receptor ,Innate immune system ,Tumor Necrosis Factor-alpha ,Interleukins ,Innate lymphoid cell ,FOXP3 ,Dendritic cell ,Acquired immune system ,3. Good health ,030104 developmental biology ,Immune System Diseases ,Interferons ,030215 immunology ,Cytokines ,interleukins ,T cells ,B cells ,dendritic cells ,innate immune response ,adaptive immune response ,humoral immune response ,allergy and asthma - Abstract
There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF- β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively). Studies of transgenic or gene- deficient mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided essential information about their functions. Here we review recent developments on IL-1 to IL-38, TNF-α, TGF-β, and interferons. We highlight recent advances during the last few years in this area and extensively discuss their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases.
- Published
- 2016
23. IgE sensitization profiles differ between adult patients with severe and moderate atopic dermatitis
- Author
-
Annika Scheynius, Lena Lundeberg, Reto Crameri, Gustav Wikberg, Rudolf Valenta, Catharina Johansson, Christian Lupinek, Irene Mittermann, and University of Zurich
- Subjects
0301 basic medicine ,Male ,Allergy ,Staphylococcus ,Eczema ,Atopic Dermatitis ,Plant Science ,medicine.disease_cause ,Immunoglobulin E ,Pathology and Laboratory Medicine ,Allergen ,10183 Swiss Institute of Allergy and Asthma Research ,Allergies ,Medicine and Health Sciences ,Staphylococcus Aureus ,Sensitization ,Mites ,Multidisciplinary ,biology ,Allergic Diseases ,Plant Anatomy ,Atopic dermatitis ,Plants ,Middle Aged ,Recombinant Proteins ,3. Good health ,Bacterial Pathogens ,medicine.anatomical_structure ,Medical Microbiology ,Malassezia sympodialis ,Medicine ,Pollen ,Female ,Malassezia ,Pathogens ,Research Article ,Adult ,Arthropoda ,Adolescent ,Science ,Immunology ,Immunoblotting ,Molecular Probe Techniques ,610 Medicine & health ,Dermatology ,1100 General Agricultural and Biological Sciences ,Research and Analysis Methods ,Microbiology ,Dermatitis, Atopic ,03 medical and health sciences ,Young Adult ,1300 General Biochemistry, Genetics and Molecular Biology ,medicine ,otorhinolaryngologic diseases ,Animals ,Humans ,Grasses ,Molecular Biology Techniques ,Microbial Pathogens ,Molecular Biology ,Aged ,Skin Tests ,House dust mite ,1000 Multidisciplinary ,Bacteria ,Organisms ,Biology and Life Sciences ,Allergens ,biology.organism_classification ,medicine.disease ,Invertebrates ,030104 developmental biology ,Case-Control Studies ,biology.protein ,Cats ,Clinical Immunology ,Clinical Medicine ,Biomarkers - Abstract
BackgroundAtopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors.AimTo characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens.MethodologyAdult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins.ResultsIgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD.ConclusionWe have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD.
- Published
- 2016
24. The Powerful Combination of Phage Surface Display of cDNA Libraries and High Throughput Screening
- Author
-
Rimantas Kodzius and Reto Crameri
- Subjects
Cloning ,Messenger RNA ,DNA, Complementary ,medicine.diagnostic_test ,cDNA library ,High-throughput screening ,Organic Chemistry ,General Medicine ,Computational biology ,Biology ,Bioinformatics ,Computer Science Applications ,Protein structure ,Western blot ,Drug Discovery ,medicine ,Combinatorial Chemistry Techniques ,Bacteriophages ,Cloning, Molecular ,Gene ,Selection (genetic algorithm) - Abstract
Phage surface display of cDNA libraries facilitates cloning, expression and rapid selection of functional gene products physically linked to their genetic information through gene product-ligand interactions. Efficient screening technologies based on selective enrichment of clones expressing desired gene products allows, within a short time, the isolation of all ligand-specific clones that are present in a library. Manual identification of clones by restriction analysis and random sequencing is unlike to be successful for the isolation of gene products derived from rare mRNA species resulting from selection of the libraries using polyvalent ligands like serum from patients. Here we describe rapid handling of large numbers of individual clones selected from molecular libraries displayed on phage surface using the power of robotics-based high throughput screening. The potential of the combination of cDNA-phage surface display, with selection for specific interactions by functional screening and robotic technology is illustrated by the isolation of more sequences potentially encoding IgE-binding proteins than postulated from Western blot analyses using extracts derived from raw material of complex allergenic sources. The subsequent application of functional enrichment and robotics-based screening will facilitate the rapid generation of information about the repertoire of protein structures involved in allergic diseases.
- Published
- 2012
25. Equine insect bite hypersensitivity: what do we know?
- Author
-
Jozef Janda, Eman Hamza, Eliane Isabelle Marti, Anna Schaffartzik, Reto Crameri, Claudio Rhyner, University of Zurich, and Marti, E
- Subjects
Allergy ,040301 veterinary sciences ,Regulatory T cell ,medicine.medical_treatment ,3400 General Veterinary ,Immunology ,Dermatitis ,610 Medicine & health ,Cross Reactions ,Ceratopogonidae ,Immunoglobulin E ,T-Lymphocytes, Regulatory ,0403 veterinary science ,03 medical and health sciences ,Th2 Cells ,0302 clinical medicine ,Immune system ,Antigen ,10183 Swiss Institute of Allergy and Asthma Research ,medicine ,Animals ,Simuliidae ,Horses ,Salivary Proteins and Peptides ,Antigen-presenting cell ,2403 Immunology ,General Veterinary ,biology ,Insect Bites and Stings ,04 agricultural and veterinary sciences ,Immunotherapy ,Allergens ,Culicoides ,biology.organism_classification ,medicine.disease ,3. Good health ,medicine.anatomical_structure ,biology.protein ,Insect Proteins ,Horse Diseases ,030215 immunology - Abstract
Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin and with stimulated peripheral blood mononuclear cells. Various studies have shown IBH to be associated with IgE-mediated reactions against salivary antigens from Culicoides spp. However, until recently, the causative allergens had not been characterized at the molecular level. A major advance has now been made, as 11 Culicoides salivary gland proteins have been identified as relevant allergens for IBH. Currently, there is no satisfactory treatment of IBH. Characterization of the main allergens for IBH and understanding what mechanisms induce a healthy or allergic immune response towards these allergens may help to develop new treatment strategies, such as immunotherapy.
- Published
- 2012
- Full Text
- View/download PDF
26. Immunoglobulin E-binding autoantigens: biochemical characterization and clinical relevance
- Author
-
Reto Crameri, University of Zurich, and Crameri, R
- Subjects
Protein family ,Immunology ,610 Medicine & health ,medicine.disease_cause ,Immunoglobulin E ,Autoantigens ,Epitope ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,10183 Swiss Institute of Allergy and Asthma Research ,Hypersensitivity ,medicine ,Animals ,Humans ,Immunology and Allergy ,030304 developmental biology ,2403 Immunology ,0303 health sciences ,biology ,Effector ,Molecular Mimicry ,3. Good health ,Molecular mimicry ,2723 Immunology and Allergy ,biology.protein ,Thioredoxin ,030215 immunology - Abstract
Although immediate-Type I skin reactions to human dander have been described six decades ago, only the recent application of molecular biology to allergology research allowed fast and detailed characterization of IgE-binding autoantigens. These can be functionally subdivided into three classes: (1) self-antigens with sequence homology to environmental allergens belonging to the class of phylogenetically conserved proteins, (2) self-antigens without sequence homology to known environmental allergens, and (3) chemically modified self-antigens deriving from workplace exposure. As environmental allergens, also IgE-binding autoantigens belong to different protein families without common structural features that would explain their IgE-binding capability. Many of the self-antigens showing sequence homology to environmental allergens, are phylogenetically conserved proteins like manganese dependent superoxide dismutase, thioredoxin or cyclopilin. Their IgE-binding capability can be explained by molecular mimicry resulting from shared B-cell epitopes. A common factor of IgE-binding self-antigens without sequence homology to known environmental allergens is that they elicit IgE responses only in individuals suffering from long-lasting atopic diseases. In contrast, IgE-mediated reactions to modified self-antigens might be explained with the generation of novel B-cell epitopes. Chemically modified self-antigens are likely to be recognized as non-self by the immune system. The clinical relevance of IgE responses to self-antigens remains largely unclear. Well documented is their ability to induce immediate Type I skin reactions in vivo, and to induce mediator release from effector cells of sensitized individuals in vitro. Based on these observations it is reasonable to assume that IgE-mediated cross-linking of FcRIε receptors on effector cells can elicit the same symptoms as those induced by environmental allergens, and this could explain exacerbations of chronic allergic diseases in the absence of external exposure. However, because most of the described IgE-binding self-antigens are intracellular proteins normally not accessible for antigen-antibody interactions, local release of the antigens is required to explain the induction of symptoms.
- Published
- 2011
27. IgE-binding epitopes: a reappraisal
- Author
-
Reto Crameri and Rob C. Aalberse
- Subjects
0303 health sciences ,biology ,business.industry ,Repertoire ,Immunology ,medicine.disease ,Immunoglobulin E ,medicine.disease_cause ,Cross-reactivity ,Epitope ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Allergen ,Epitope mapping ,Food allergy ,medicine ,biology.protein ,Immunology and Allergy ,Antibody ,business ,030304 developmental biology ,030215 immunology - Abstract
Here, we discuss various questions related to IgE epitopes: What are the technical possibilities and pitfalls, what is currently known, how can we put this information into hypothetical frameworks and the unavoidable question: how useful is this information for patient care or allergenicity prediction? We discuss the information obtained by (i) 3D structures of allergen-antibody complexes; (ii) analysis of allergen analogues; (iii) mimics without obvious structural similarity; (iv) mAbs competing with IgE; (v) repertoire analysis of cloned IgEs, and other developments. Based on limited data, four suggestions are presented in the literature: (i) IgE might be more cross-reactive than IgG; (ii) IgE might be more often directed to immunologically 'uninviting' surfaces; (iii) IgE epitopes may tend to cluster and (iv) IgE paratopes might have a higher intrinsic flexibility. While these are not proven facts, they still can generate hypotheses for future research. The hypothesis is put forward that the IgE repertoire of switched B-cells is less influenced by positive selection, because positive selection might not be able to rescue IgE-switched B cells. While this might be of interest for the discussion about mechanisms leading to allergen-sensitization, we need to be modest in answering the 'clinical relevance' question. Current evidence indicates the IgE-epitope repertoire is too big to make specific IgE epitopes a realistic target for diagnosis, treatment or allergenicity prediction. In-depth analysis of a few selected IgE epitope-peptides or mimitopes derived from allergen-sequences and from random peptide libraries, respectively, might well prove rewarding in relation to diagnosis and prognosis of allergy, particularly food allergy.
- Published
- 2011
28. HIV interferes with SOCS-1 and -3 expression levels driving immune activation
- Author
-
David Nadal, Rahel Byland, Roberto F. Speck, Stefan Baenziger, Regina C. Miller, Annette Audigé, Erika Schlaepfer, Reto Crameri, Sabine Zeller, University of Zurich, and Speck, R F
- Subjects
Adult ,T-Lymphocytes ,Immunology ,610 Medicine & health ,HIV Infections ,Suppressor of Cytokine Signaling Proteins ,Biology ,stat ,10234 Clinic for Infectious Diseases ,03 medical and health sciences ,Suppressor of Cytokine Signaling 1 Protein ,0302 clinical medicine ,Immune system ,10183 Swiss Institute of Allergy and Asthma Research ,Humans ,Immunology and Allergy ,RNA, Messenger ,STAT4 ,Cells, Cultured ,Janus Kinases ,030304 developmental biology ,2403 Immunology ,0303 health sciences ,JAK-STAT signaling pathway ,Middle Aged ,3. Good health ,STAT Transcription Factors ,Lymphatic system ,Gene Expression Regulation ,10036 Medical Clinic ,Suppressor of Cytokine Signaling 3 Protein ,030220 oncology & carcinogenesis ,2723 Immunology and Allergy ,STAT protein ,Signal transduction ,Ex vivo ,Signal Transduction - Abstract
HIV infection is characterized by sustained immune activation, which is reflected by activated T cells and, in particular, by increased levels of phosphorylated STAT proteins. Here, we hypothesized that T-cell activation in HIV infection is partially due to the inability of SOCS-1 and SOCS-3 to control the JAK/STAT pathway. We found higher levels of SOCS-1/3 mRNA levels in CD4(+) T cells of HIV-infected patients than in healthy controls. However, SOCS protein levels were lower, explaining the lack of attenuation of the JAK/STAT pathway. Infection of CD4(+) T cells alone did not activate STATs, while ex vivo infection of PBMC did, indicating that non-T cells critical for shaping the immune response, e.g. DC were responsible for the STAT-1 activation. Supernatants from ex vivo-infected PBMC transferred to CD4(+) T cells induced JAK/STAT activation, pointing to a central role of soluble factors. Notably, over-expression of SOCS-1/3 in CD4(+) T cells prevented JAK/STAT activation. Thus, HIV infection interferes with SOCS-1/3 expression driving immune activation. Sustained immune activation disrupts the lymphoid system and favors HIV replication since HIV preferentially infects activated cells. We speculate that regulating SOCS may be a potential way to counteract immune activation in HIV disease.
- Published
- 2011
29. Selective cloning, characterization, and production of the Culicoides nubeculosus salivary gland allergen repertoire associated with equine insect bite hypersensitivity
- Author
-
Philip S. Mellor, Sigurbjörg Torsteinsdóttir, Eliane Isabelle Marti, Claudio Rhyner, Reto Crameri, Anna Schaffartzik, University of Zurich, and Rhyner, C
- Subjects
040301 veterinary sciences ,3400 General Veterinary ,Immunology ,610 Medicine & health ,Ceratopogonidae ,Immunoglobulin E ,medicine.disease_cause ,Salivary Glands ,law.invention ,0403 veterinary science ,Mice ,03 medical and health sciences ,Allergen ,Western blot ,10183 Swiss Institute of Allergy and Asthma Research ,law ,Complementary DNA ,Hypersensitivity ,medicine ,Animals ,Horses ,Cloning, Molecular ,Gene Library ,Skin Tests ,030304 developmental biology ,2403 Immunology ,0303 health sciences ,Base Sequence ,General Veterinary ,biology ,Salivary gland ,medicine.diagnostic_test ,cDNA library ,Insect Bites and Stings ,DNA ,04 agricultural and veterinary sciences ,Allergens ,Intradermal Tests ,Fusion protein ,Molecular biology ,medicine.anatomical_structure ,biology.protein ,Recombinant DNA ,Horse Diseases ,Protein Binding - Abstract
Salivary gland proteins of Culicoides spp. have been suggested to be among the main allergens inducing IgE-mediated insect bite hypersensitivity (IBH), an allergic dermatitis of the horse. The aim of our study was to identify, produce and characterize IgE-binding salivary gland proteins of Culicoides nubeculosus relevant for IBH by phage surface display technology. A cDNA library constructed with mRNA derived from C. nubeculosus salivary glands was displayed on the surface of filamentous phage M13 and enriched for clones binding serum IgE of IBH-affected horses. Ten cDNA inserts encoding putative salivary gland allergens were isolated and termed Cul n 2 to Cul n 11. However, nine cDNA sequences coded for truncated proteins as determined by database searches. The cDNA sequences were amplified by PCR, subcloned into high level expression vectors and expressed as hexahistidine-tagged fusion proteins in Escherichia coli. Preliminary ELISA results obtained with these fusions confirmed the specific binding to serum IgE of affected horses. Therefore, the putative complete open reading frames derived from BLAST analyses were isolated by RACE-PCR and subcloned into expression vectors. The full length proteins expressed in Escherichia coli showed molecular masses in the range of 15.5-68.7 kDa in SDS-PAGE in good agreement with the masses calculated from the predicted protein sequences. Western blot analyses of all recombinant allergens with a serum pool of IBH-affected horses showed their ability to specifically bind serum IgE of sensitized horses, and ELISA determinations yielded individual horse recognition patterns with a frequency of sensitization ranging from 13 to 57%, depending on the allergen tested. The in vivo relevance of eight of the recombinant allergens was demonstrated in intradermal skin testing. For the two characterized allergens Cul n 6 and Cul n 11, sensitized horses were not available for intradermal tests. Control horses without clinical signs of IBH did not develop any relevant immediate hypersensitivity reactions to the recombinant allergens. The major contribution of this study was to provide a repertoire of recombinant salivary gland allergens repertoire from C. nubeculosus potentially involved in the pathogenesis of IBH as a starting basis for the development of a component-resolved serologic diagnosis of IBH and, perhaps, for the development of single horse tailored specific immunotherapy depending on their component-resolved sensitization patterns.
- Published
- 2011
30. MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine
- Author
-
Fernando D. Martinez, U. Baumgartner, Angela Neubauer, Mübeccel Akdis, D. S. Postma, Dieter Maier, Jan Lötvall, Steffen Lau, E. Eveno, S. Palkonen, Miguel López-Botet, Marek L. Kowalski, S. Guerra, Raphaëlle Varraso, Isabelle Momas, Christian Lupinek, Torsten Zuberbier, Kai-Håkon Carlsen, Sam Oddie, Elina Toskala, Karin C. Lødrup-Carlsen, John Wright, Josep M. Antó, A. J. M. Van Oosterhout, Tari Haahtela, Isabelle Pin, Reto Crameri, F. Ballester, Bénédicte Jacquemin, D. Smagghe, Cezmi A. Akdis, Thomas Keil, Claus Bachert, E. Rial-Sebbag, A. Arno, Marjan Kerkhof, Valérie Siroux, Charles Auffray, Jordi Mestres, Manolis Kogevinas, Martijn C. Nawijn, Isabella Annesi-Maesano, Xavier Basagaña, F. Rance, Margitta Worm, Francine Kauffmann, Jordi Sunyer, Bert Brunekreef, J. Garcia-Aymerich, Mika J. Mäkelä, Rudolf Valenta, P. Van Cauwenberge, Joachim Heinrich, Sakari Reitamo, Bart N. Lambrecht, Jean Bousquet, Christophe Pison, M. Salapatas, Anne Cambon-Thomsen, L. von Hertzen, Gerard H. Koppelman, M. Torrent, Francesco Forastiere, Carsten Bindslev-Jensen, D. Hirsch, Cisca Wijmenga, Magnus Wickman, Hamida Hammad, and Leda Chatzi
- Subjects
Mechanism (biology) ,business.industry ,Systems biology ,Immunology ,Computational biology ,3. Good health ,Systems medicine ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Health care ,Global health ,Immunology and Allergy ,media_common.cataloged_instance ,Medicine ,Identification (biology) ,030212 general & internal medicine ,European union ,business ,Functional genomics ,media_common - Abstract
The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.
- Published
- 2011
31. HAX1 deficiency: Impact on lymphopoiesis and B-cell development
- Author
-
Susanne Wolkerstorfer, Roger Schibli, Elke Luger, Nadja Zaborsky, Michael Huemer, S. Feichtner, Marinus C. Lamers, Gertrude Achatz-Straussberger, Reto Crameri, Doris Peckl-Schmid, Elisabeth Schwaiger, Sebastian Königsberger, Katrin Moser, Iris K. Gratz, Gernot Achatz, University of Zurich, and Achatz, G
- Subjects
Receptors, CXCR4 ,Adoptive cell transfer ,Cell Survival ,Lymphocyte ,Immunology ,610 Medicine & health ,Spleen ,Thymus Gland ,Biology ,CXCR4 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,10183 Swiss Institute of Allergy and Asthma Research ,Bone Marrow ,Cell Movement ,medicine ,Animals ,Immunology and Allergy ,Lymphopoiesis ,B cell ,030304 developmental biology ,Mice, Knockout ,2403 Immunology ,B-Lymphocytes ,Mice, Inbred BALB C ,0303 health sciences ,Intracellular Signaling Peptides and Proteins ,Proteins ,medicine.anatomical_structure ,Gene Expression Regulation ,Apoptosis ,030220 oncology & carcinogenesis ,2723 Immunology and Allergy ,Cancer research ,Leukocyte Common Antigens ,Bone marrow - Abstract
HAX1 was originally described as HS1-associated protein with a suggested function in receptor-mediated apoptotic and proliferative responses of lymphoid cells. Recent publications refer to a complex and multifunctional role of this protein. To investigate the in vivo function of HAX1 (HS1-associated protein X1) in B cells, we generated a Hax1-deficient mouse strain. Targeted deletion of Hax1 resulted in premature death around the age of 12 wk accompanied by a severe reduction of lymphocytes in spleen, thymus and bone marrow. In the bone marrow, all B-cell populations were lost comparably. In the spleen, B220(+) cells were reduced by almost 70%. However, as investigated by adoptive transfer experiments, this impairment is not exclusively B-cell intrinsic and we hypothesize that a HAX1-deficient environment cannot sufficiently provide the essential factors for proper lymphocyte development, trafficking and survival. Hax1(-/-) B cells show a significantly reduced expression of CXCR4, which might have an influence on the observed defects in B-cell development. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
- Published
- 2010
32. Cloning, production and characterization of antigen 5 like proteins from Simulium vittatum and Culicoides nubeculosus, the first cross-reactive allergen associated with equine insect bite hypersensitivity
- Author
-
Anna Schaffartzik, Reto Crameri, Eliane Isabelle Marti, Claudio Rhyner, University of Zurich, and Rhyner, C
- Subjects
Allergy ,040301 veterinary sciences ,3400 General Veterinary ,Immunology ,610 Medicine & health ,Enzyme-Linked Immunosorbent Assay ,Wasp Venoms ,Biology ,Cross Reactions ,Immunoglobulin E ,medicine.disease_cause ,Ceratopogonidae ,Cross-reactivity ,Epitope ,0403 veterinary science ,03 medical and health sciences ,Blood serum ,Allergen ,Western blot ,10183 Swiss Institute of Allergy and Asthma Research ,medicine ,Hypersensitivity ,Animals ,Simuliidae ,Horses ,Cloning, Molecular ,030304 developmental biology ,Skin Tests ,0303 health sciences ,2403 Immunology ,General Veterinary ,medicine.diagnostic_test ,Insect Bites and Stings ,04 agricultural and veterinary sciences ,Allergens ,Culicoides ,biology.organism_classification ,medicine.disease ,Molecular biology ,Recombinant Proteins ,3. Good health ,biology.protein ,Horse Diseases - Abstract
Insect bite hypersensitivity (IBH) is an IgE-mediated seasonal dermatitis of the horses associated with bites of Simulium (black fly) and Culicoides (midge) species. Although cross-reactivity between Simulium and Culicoides salivary gland extracts has been demonstrated, the molecular nature of the allergens responsible for the observed cross-reactivity remains to be elucidated. In this report we demonstrate for the first time in veterinary medicine that a homologous allergen, present in the salivary glands of both insects, shows extended IgE cross-reactivity in vitro and in vivo. The cDNA sequences coding for both antigen 5 like allergens termed Sim v 1 and Cul n 1 were amplified by PCR, subcloned in high level expression vectors, and produced as [His](6)-tagged proteins in Escherichia coli. The highly pure recombinant proteins were used to investigate the prevalence of sensitization in IBH-affected horses by ELISA and their cross-reactive nature by Western blot analyses, inhibition ELISA and intradermal skin tests (IDT). The prevalence of sensitization to Sim v 1 and Cul n 1 among 48 IBH-affected horses was 37% and 35%, respectively. In contrast, serum IgE levels to both allergens in 24 unaffected horses did not show any value above background. Both proteins strongly bound serum IgE from IBH-affected horses in Western blot analyses, demonstrating the allergenic nature of the recombinant proteins. Extended inhibition ELISA experiments clearly showed that Sim v 1 in fluid phase is able to strongly inhibit binding of serum IgE to solid phase coated Cul n 1 in a concentration dependent manner and vice versa. This crucial experiment shows that the allergens share common IgE-binding epitopes. IDT with Sim v 1 and Cul n 1 showed clear immediate and late phase reactions to the allergen challenges IBH-affected horses, whereas unaffected control horses do not develop relevant immediate hypersensitivity reactions. In some horses, however, mild late phase reactions were observed 4h post-challenge, a phenomenon reported to occur also in challenge experiments with Simulium and Culicoides crude extracts probably related to lipopolysaccaride contaminations which are also present in E. coli-expressed recombinant proteins. In conclusion our data demonstrate that IgE-mediated cross-reactivity to homologous allergens, a well-known clinically relevant phenomenon in human allergy, also occurs in veterinary allergy.
- Published
- 2010
- Full Text
- View/download PDF
33. Novel immunotherapeutic approaches for allergy and asthma
- Author
-
Mübeccel Akdis, Cezmi A. Akdis, Liam O'Mahony, Reto Crameri, University of Zurich, and O'Mahony, L
- Subjects
Allergy ,medicine.medical_treatment ,T cell ,Immunology ,610 Medicine & health ,Immunoglobulin E ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,10183 Swiss Institute of Allergy and Asthma Research ,Immunity ,Hypersensitivity ,Immunology and Allergy ,Medicine ,Animals ,Humans ,030304 developmental biology ,Asthma ,2403 Immunology ,0303 health sciences ,biology ,business.industry ,Immunotherapy ,medicine.disease ,3. Good health ,medicine.anatomical_structure ,2723 Immunology and Allergy ,biology.protein ,business ,030215 immunology - Abstract
The immune response is a tightly regulated process, which normally results in protection from infection and tolerance of innocuous environmental antigens. However, in allergic disease, the activated immune response results in a chronic pro-inflammatory state characterized by antibody secretion (IgE) and T cell activation to normally well-tolerated antigens. Currently, the treatment of allergic disease is focused on the suppression of key inflammatory mediators or inflammatory cell populations and include anti-histamines, anti-leukotrienes,#x03B2;2 adrenergic receptor agonists and corticosteroids. However, these approaches only provide a temporary suppression of disease symptoms. Successful long-term treatment can only be provided by allergen-specific immunotherapy (allergen-SIT), which restores normal immunity against allergens. This review will discuss novel approaches to the management of allergy and asthma by targeting the T regulatory cell via modulation of the commensal microbiota and allergen-SIT.
- Published
- 2010
- Full Text
- View/download PDF
34. Modular antigen-translocation as a novel vaccine strategy for allergen-specific immunotherapy
- Author
-
Reto Crameri, Thomas M. Kündig, and Cezmi A. Akdis
- Subjects
Hypersensitivity, Immediate ,medicine.medical_treatment ,Immunology ,Antigen presentation ,Major histocompatibility complex ,Immunomodulation ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Antigen ,Humans ,Immunology and Allergy ,Medicine ,030223 otorhinolaryngology ,Desensitization (medicine) ,Antigen Presentation ,Vaccines ,Vaccines, Synthetic ,biology ,business.industry ,Drug Administration Routes ,Histocompatibility Antigens Class II ,Specific immunotherapy ,Immunotherapy ,Allergens ,3. Good health ,Protein Transport ,Desensitization, Immunologic ,Dermatology clinic ,biology.protein ,business ,030215 immunology - Abstract
PURPOSE OF REVIEW The purpose of the present review is to describe recent approaches aimed at improving the treatment of allergic diseases through allergen specific immunotherapy (SIT). Special emphasis will be given to the approach based on specific targeting of the major histocompatibility complex (MHC) class II antigen presentation pathway. RECENT FINDINGS It is well recognized that IgE mediated allergic diseases including rhinitis atopic eczema and allergic asthma are increasing worldwide to a pandemic dimension. The only curative treatment remains allergen SIT which however requires a long treatment time of 3 5 years with up to 80 injections to confer protection. Recent findings strongly indicate that the treatment time and the number of injections could be drastically reduced by turning immunotherapy to a true vaccination. Direct injection of allergen extracts into the inguinal lymph nodes and targeting the MHC class II antigen presentation pathway by recombinant modular antigen translocating vaccines have the potential to cure allergic diseases in a very short time. SUMMARY The mechanisms of allergic inflammation can be divided into four distinct stages: T cell activation organ selective homing survival/reactivation and effector functions. On the basis of this new knowledge several novel concepts aimed at treating allergic diseases have been developed. The area of allergen SIT is experiencing exciting developments. Reciprocal regulation of effector and regulatory T cell subsets is being more and more used to develop novel strategies for immunomodulation.
- Published
- 2009
35. Molecular and immunological characterization of Asp f 34, a novel major cell wall allergen ofAspergillus fumigatus
- Author
-
Reto Crameri, Claudio Rhyner, Sabine Zeller, A. I. Kirsch, Andreas G. Glaser, and Günter Menz
- Subjects
Adult ,Male ,Molecular Sequence Data ,Immunology ,Immunoglobulin E ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Aspergillus fumigatus ,law.invention ,Microbiology ,Fungal Proteins ,Allergen ,Antibody Specificity ,Cell Wall ,law ,Complementary DNA ,medicine ,Humans ,Immunology and Allergy ,Amino Acid Sequence ,Cloning, Molecular ,Antibodies, Fungal ,Aged ,Skin Tests ,Aspergillus ,Fungal protein ,Sequence Homology, Amino Acid ,biology ,Aspergillosis, Allergic Bronchopulmonary ,Allergens ,Middle Aged ,biology.organism_classification ,Recombinant Proteins ,Molecular Weight ,Leukocytes, Mononuclear ,biology.protein ,Recombinant DNA ,Female ,Cell Division - Abstract
Background: Although fungal spores have been recognized as triggers of respiratory allergy and asthma, only two allergenic fungal cell wall components have so far been described. Methods: Eighty-one sequences derived from an Aspergillus fumigatus cDNA library encoding putative allergens were examined for the presence of cell wall components. A new allergen (Asp f 34) was evaluated by Western blots, enzyme-linked immunosorbent assay (ELISA), peripheral blood mononuclear cell (PBMC) proliferation assays, and skin prick test (SPT). Results: The cDNA encoding Asp f 34 contained an open reading frame predicting a protein of 185 amino acids with a molecular weight of 19.38 kDa, showing sequence homology to phiA, an essential protein for the formation of conidia in the genus Aspergillus. The recombinant Asp f 34 was binding IgE from sensitized individuals in Western blots. An ELISA survey showed that 94% of the ABPA and 46% of the A. fumigatus-sensitized individuals tested had Asp f 34-specific serum IgE. Asp f 34 induced allergen-specific proliferation exclusively of PBMCs from patients sensitized to the allergen. Eight patients with anti-Asp f 34 serum IgE tested reacted positively in SPT, whereas four A. fumigatus-sensitized individuals without Asp f 34-specific IgE and eight healthy controls scored negatively. Conclusions: A cell wall protein of the phialides of A. fumigatus was identified as a major allergen. Asp f 34 belongs to the Aspergillus-specific proteins of the phiA family and has relevant potential for a specific diagnosis of Aspergillus sensitization.
- Published
- 2009
36. The vacuolar serine protease, a cross-reactive allergen from Cladosporium herbarum
- Author
-
Raphael C. Panzani, Reto Crameri, Klaus Richter, Verena Pöll, Birgit Simon-Nobbe, Friedrich Lottspeich, Horng-Der Shen, Michael Breitenbach, Raphaela Rid, Wolfgang Hemmer, Oliver Dissertori, Peter Lackner, Ursula Denk, Adriano Mari, University of Zurich, and Simon-Nobbe, B
- Subjects
Models, Molecular ,Proteases ,Molecular Sequence Data ,Immunology ,610 Medicine & health ,Cross Reactions ,Microbiology ,Aspergillus fumigatus ,Fungal Proteins ,Serine ,10183 Swiss Institute of Allergy and Asthma Research ,Sequence Analysis, Protein ,1312 Molecular Biology ,medicine ,Amino Acid Sequence ,Cloning, Molecular ,Molecular Biology ,Serine protease ,2403 Immunology ,Base Sequence ,Sequence Homology, Amino Acid ,biology ,cDNA library ,Serine Endopeptidases ,food and beverages ,Allergens ,Penicillium chrysogenum ,biology.organism_classification ,medicine.drug_formulation_ingredient ,Biochemistry ,Cladosporium herbarum ,Vacuoles ,Penicillium ,biology.protein ,Cladosporium ,Epitope Mapping - Abstract
Subtilisin-like serine proteases make up one of the most important allergen-families regarding the number of individual allergens. Previously, fungal subtilisin-like serine proteases have been identified from Aspergillus-, Penicillium-, and Trichophyton-species having a prevalence of IgE-reactivity between 33% and 80%. Since IgE-cross-reactivity is a common phenomenon within fungal species we wanted to know whether this protein also represents an allergen in Cladosporium herbarum. Hence, a screening of a C. herbarum cDNA library was performed using the coding sequence of the Penicillium oxalicum vacuolar serine protease (Pen o 18) as hybridization probe, ending up with a full-length clone. Biochemical and immunological characterization of this clone revealed that C. herbarum vacuolar serine protease most likely is synthesized as a precursor with an N-terminal pro-enzyme sequence and represents a minor allergen (Cla h 9) with a prevalence of IgE-reactivity of 15.5%. Furthermore Cla h 9 specifically reacted with the two monoclonal antibodies FUM20 and PCM39, as do the vacuolar serine proteases from Aspergillus fumigatus and Penicillium species. Investigation of IgE-cross-reactivity between Cla h 9 and other fungal serine proteases revealed that cross-reactivity is higher between vacuolar than alkaline serine proteases. IgE-epitope mapping of Cla h 9 was done in order to test whether four Cla h 9-peptides having a high sequence homology to previously determined Pen ch 18-IgE-epitopes also harbour IgE-epitopes. Three-dimensional models of the vacuolar serine proteases from C. herbarum and Penicillium chrysogenum were generated for the three-dimensional localization of the Cla h 9- and Pen ch 18- IgE-reactive and -non-reactive peptides. Taken together a new C. herbarum allergen has been identified, which may be useful in a molecule-based approach of C. herbarum allergy-diagnosis and -therapy. Moreover, Cla h 9 represents a further member of the subtilisin-like serine protease allergen-family, which stresses the importance of these proteins with respect to fungal IgE-cross-reactivity.
- Published
- 2009
37. Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema
- Author
-
Cezmi A. Akdis, Peter Schmid-Grendelmeier, Reto Crameri, Sabine Zeller, Norbert Meyer, Claudio Rhyner, University of Zurich, and Crameri, R
- Subjects
Adult ,Male ,Allergy ,Immunology ,610 Medicine & health ,Immunoglobulin E ,Autoantigens ,law.invention ,Dermatitis, Atopic ,Atopy ,Antigen-Antibody Reactions ,03 medical and health sciences ,0302 clinical medicine ,law ,10183 Swiss Institute of Allergy and Asthma Research ,medicine ,Immunology and Allergy ,Humans ,Genomic library ,030304 developmental biology ,Gene Library ,0303 health sciences ,2403 Immunology ,biology ,cDNA library ,10177 Dermatology Clinic ,medicine.disease ,Recombinant Proteins ,3. Good health ,Basophils ,Blot ,Immunoglobulin G ,biology.protein ,Recombinant DNA ,2723 Immunology and Allergy ,Female ,Antibody ,030215 immunology - Abstract
Background Atopic eczema (AE) is the most common chronic inflammatory skin disease. Recent data demonstrate the presence of autoreactive serum IgE antibodies correlating with the severity of the disease. Objective Although several IgE-binding self-antigens have been reported, the whole repertoire of IgE-binding self-antigens is unknown. We aimed to estimate the repertoire size of autoreactive proteins related to AE and clone, produce, and characterize humoral and T-cell responses against novel self-antigens. Methods Phage surface–displayed human cDNA libraries were enriched for clones binding to serum IgE from patients with AE and screened by using high-throughput technology. Selected clones were used to produce the encoded proteins, to test their IgE-binding ability in Western blots and ELISAs, and their ability to induce mediator release from basophils of sensitized individuals. Results One hundred forty sequences encoding potential IgE-binding self-antigens associated with AE were identified. Sixteen sequences encoded already described self-antigens. Three new sequences showed homology with environmental allergens, 86 encoded known human proteins, 7 predicted proteins, and 28 showed sequence identity with genomic contigs. Immunoblotting and ELISA experiments demonstrated the presence of IgE antibodies in sera from patients with AE to 5 selected recombinant self-antigens and their ability to induce mediator release from basophils of patients with AE who have self-antigen–specific IgE antibodies. Conclusion These data demonstrate a broad spectrum of at least 140 IgE-binding self-antigens associated with AE. By binding IgE antibodies or activating specific T cells, they might promote, perpetuate, or both existing skin inflammation.
- Published
- 2009
- Full Text
- View/download PDF
38. Report of the 3rd Havemeyer workshop on allergic diseases of the Horse, Hólar, Iceland, June 2007
- Author
-
Fiona M. Cunningham, Bettina Wagner, P. Horin, Vilhjálmur Svansson, Douglas F. Antczak, Eman Hamza, G. Olafsdottir, Eliane Isabelle Marti, Jean-Pierre Lavoie, Reto Crameri, A D Wilson, Sigurbjörg Torsteinsdóttir, M. Heimann, G. Kolm-Stark, M. Derer, David W. Horohov, Eve Ramery, A. Schaffartzik, R. Frey, D.P. Lunn, T. S. Bjornsdottir, C.L. Russell, V. Gerber, and Sigríður Björnsdóttir
- Subjects
Allergy ,General Veterinary ,Incidence (epidemiology) ,Immunology ,medicine ,Allergic dermatitis ,Horse ,Disease ,Biology ,medicine.disease ,INSECT BITE HYPERSENSITIVITY ,Recurrent airway obstruction - Abstract
Allergic diseases occur in most mammals, although some species such as humans, dogs and horses seem to be more prone to develop allergies than others. In horses, insect bite hypersensitivity (IBH), an allergic dermatitis caused by bites of midges, and recurrent airway obstruction (RAO), a hyperreactivity to stable born dust and allergens, are the two most prevalent allergic diseases. Allergic diseases involve the interaction of three major factors: (i) genetic constitution, (ii) exposure to allergens, and (iii) a dysregulation of the immune response determined by (i) and (ii). However, other environmental factors such as infectious diseases, contact with endotoxin and degree of infestation with endoparasites have been shown to influence the prevalence of allergic diseases in humans. How these factors may impact upon allergic disease in the horse is unknown at this time. The 3rd workshop on Allergic Diseases of the Horse, with major sponsorship from the Havemeyer Foundation, was held in Holar, Iceland, in June 2007 and focussed on immunological and genetic aspects of IBH and RAO. This particular venue was chosen because of the prevalence of IBH in exported Icelandic horses. The incidence of IBH is significantly different between Icelandic horses born in Europe or North America and those born in Iceland and exported as adults. Although the genetic factors and allergens are the same, exported adult horses show a greater incidence of IBH. This suggests that environmental or epigenetic factors may contribute to this response. This report summarizes the present state of knowledge and summarizes important issues discussed at the workshop.
- Published
- 2008
39. Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper
- Author
-
Peter H. Howarth, Peter Burney, SE Dahlen, G.W. Canonica, W. J. Fokkens, Stephen R. Durham, Marc Humbert, Thomas Bieber, Adnan Custovic, Sylvain Lehmann, Francine Kauffmann, Philippe-Jean Bousquet, J P Zock, Bodo Niggemann, Ewa Nizankowska-Mogilnicka, Marek L. Kowalski, Jan L. Brozek, Gianni Passalacqua, Pascal Demoly, Nikolaos G. Papadopoulos, Bart N. Lambrecht, Sergio Bonini, Torsten Zuberbier, C. Holland, Jean Bousquet, R. G. Van Wijk, Magnus Wickman, Hans-Uwe Simon, Holger J. Schünemann, Rudolf Valenta, Reto Crameri, Bénédicte Leynaert, Sebastian L. Johnston, Elina Toskala, Karin C. Lødrup-Carlsen, Lars-Olaf Cardell, Cezmi A. Akdis, Claus Bachert, Mark Gjomarkaj, Ana Todo-Bom, and J Mullol
- Subjects
0303 health sciences ,medicine.medical_specialty ,Allergy ,business.industry ,Non-allergic rhinitis ,Immunology ,Disease ,medicine.disease ,Comorbidity ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Infectious Rhinitis ,Nonallergic rhinitis ,030228 respiratory system ,Epidemiology ,medicine ,Immunology and Allergy ,business ,030304 developmental biology ,Asthma - Abstract
Nonallergic rhinitis (NAR) can be defined as a chronic nasal inflammation which is not caused by systemic IgE-dependent mechanisms. It is common and probably affects far more than 200 million people worldwide. Both children and adults are affected. However, its exact prevalence is unknown and its phenotypes need to be evaluated using appropriate methods to better understand its pathophysiology, diagnosis and management. It is important to differentiate between infectious rhinitis, allergic/NAR and chronic rhinosinusitis, as management differs for each of these cases. Characterization of the phenotype, mechanisms and management of NAR represents one of the major unmet needs in allergic and nonallergic diseases. Studies on children and adults are required in order to appreciate the prevalence, phenotype, severity and co-morbidities of NAR. These studies should compare allergic and NAR and consider different age group populations including elderly subjects. Mechanistic studies should be carried out to better understand the disease(s) and risk factors and to guide towards an improved diagnosis and therapy. These studies need to take the heterogeneity of NAR into account. It is likely that neuronal mechanisms, T cells, innate immunity and possibly auto-immune responses all play a role in NAR and may also contribute to the symptoms of allergic rhinitis.
- Published
- 2008
40. Membrane Bound IgE: The Key Receptor to Restrict High IgE Levels
- Author
-
Gernot Achatz, Marinus C. Lamers, Reto Crameri, and University of Zurich
- Subjects
biology ,Immunology ,B-cell receptor ,Naive B cell ,CD23 ,610 Medicine & health ,Plasma cell ,Immunoglobulin D ,Cell biology ,B-1 cell ,Affinity maturation ,medicine.anatomical_structure ,10183 Swiss Institute of Allergy and Asthma Research ,biology.protein ,medicine ,Immunology and Allergy ,B cell - Abstract
The membrane form of immunoglobulins (mIg) is expressed on the surface of B lymphocytes from a very early developmental stage in the bone marrow (pre B cell) until the cell finally differentiates into a plasma cell. mIgs associate with other transmembrane proteins to form the B cell antigen receptor complex (BCR). Numerous studies have confirmed that signaling through the BCR not only steers the B cell through development, but also ensures its survival in the periph- ery as a fully matured cell. During development in the bone marrow, mIg is restricted to the IgM isotype, but as soon as the B cell leaves the bone marrow to populate peripheral lymphoid organs like spleen, lymph nodes, or intestinal mucosal tissue, it starts to express IgD and in later stages of maturation IgG, IgE and IgA. Engagement of the B cell receptor trig- gers signals that control affinity maturation, memory induction, differentiation and other physiological processes in B cells. We showed that truncation of the cytoplasmic tail of mIgE in vivo results in lower serum IgE levels, decreased numbers of IgE-secreting plasma cells, and abrogation of specific secondary responses correlating with a defect in the se- lection of high-affinity antibodies during the germinal centre reaction. We conclude that the BCR is necessary at all times during antibody responses not only for the maturation process, but also for the expansion of antigen specific B cells. As a result of these findings it is obvious that the IgE antigen receptor could be a useful target molecule for therapeutic inter- vention.
- Published
- 2008
41. Kreuz- und Autoreaktivität von Allergenmolekülen aus struktureller Sicht
- Author
-
Reto Crameri, C. Rhyner, S. Zeller, and Andreas G. Glaser
- Subjects
Allergy ,medicine.drug_class ,medicine.medical_treatment ,Computational biology ,Immunotherapy ,Biology ,Monoclonal antibody ,medicine.disease ,Epitope ,law.invention ,medicine.anatomical_structure ,law ,Immunology ,medicine ,Recombinant DNA ,Immunology and Allergy ,Thioredoxin ,B cell ,Cyclophilin - Abstract
IgE-mediated cross-reactivity is frequently observed in clinical practice and results from sharing of IgE-binding B cell epitopes by phylogenetically conserved proteins. Cyclophilin, manganese-dependent superoxide dismutase and thioredoxin are clinically tested, cross-reactive pan-allergens. Remarkably, some patients with severe, long-lasting atopic diseases also show cross-reactivity to human homologs of these proteins, indicating that IgE-mediated autoreactivity might play a role in the exacerbation of chronic allergic diseases. The three-dimensional structures of an increasing number of allergens have been solved by X-ray crystallography or NMR spectroscopy. These structures cover a wide variety of different folds and combinations therefore, but no common structural feature determining the allergenicity of a protein could be derived so far from structural information. Although crystal structures do not yet answer the question, why some proteins are allergenic and some others are not, they have strongly contributed to our understanding of cross-reactivity at molecular level. Co-crystallization of an allergen with a bound monoclonal antibody Fab fragment and subsequent solution of the X-ray structure of the complex is the only method allowing the complete definition of a B cell epitope. Alternatively cross-reactive B cell epitopes can be predicted fast and reliably by determining shared features of cross-reactive allergens on sequence and structure level. This knowledge will contribute to reduce the number of molecular structures needed for diagnosis and perhaps immunotherapy of allergic diseases based on recombinant allergens and will help to develop safe and patient-tailored vaccination concepts.
- Published
- 2007
42. Allergen motifs and the prediction of allergenicity
- Author
-
Elsbeth Keller-Gautschi, Peter Schmid-Grendelmeier, Michael B. Stadler, Sylvia Miescher, Monique Vogel, Renato Truffer, Adriano Mari, Pamela Marti, Beda M. Stadler, and Reto Crameri
- Subjects
In silico ,Amino Acid Motifs ,Molecular Sequence Data ,Immunology ,Peptide ,Tropomyosin ,Cross Reactions ,Biology ,medicine.disease_cause ,Cross-reactivity ,law.invention ,Structure-Activity Relationship ,Allergen ,Penaeidae ,law ,medicine ,Consensus sequence ,Animals ,Humans ,Immunology and Allergy ,Amino Acid Sequence ,Shellfish ,chemistry.chemical_classification ,Base Sequence ,Superoxide Dismutase ,fungi ,Allergens ,Antigens, Plant ,Immunoglobulin E ,biology.organism_classification ,Molecular biology ,chemistry ,Malassezia sympodialis ,Recombinant DNA ,Sequence Alignment - Abstract
We have recently shown that the majority of allergens can be represented by allergen motifs. This observation prompted us to experimentally investigate the synthesized peptides corresponding to the in silico motifs with regard to potential IgE binding and cross-reactions with allergens. Two motifs were selected as examples to conduct in vitro studies. From the first motif, derived from allergenic MnSOD sequences, the motif stretch of the allergen Asp f 6 was selected and synthesized as a peptide (MnSOD Mot). The corresponding full-length MnSOD was also expressed in Escherichia coli and both were compared for IgE reactivity with sera of patients reacting to the MnSOD of Aspergillus fumigatus or Malassezia sympodialis. For the second motif, the invertebrate tropomyosin sequences were aligned and a motif consensus sequence was expressed as a recombinant protein (Trop Mot). The IgE reactivity of Trop Mot was analyzed in ELISA and compared to that of recombinant tropomyosin from the shrimp Penaeus aztecus (rPen a 1) in ImmunoCAP. MnSOD Mot was weakly recognized by some of the tested sera, suggesting that the IgE binding epitopes of a multimeric globular protein such as MnSOD cannot be fully represented by a motif peptide. In contrast, the motif Trop Mot showed the same IgE reactivity as shrimp full-length tropomyosin, indicating that the major allergenic reactivity of a repetitive structure such as tropomyosin can be covered by a motif peptide. Our results suggest that the motif-generating algorithm may be used for identifying major IgE binding structures of coiled-coil proteins.
- Published
- 2007
43. The Malassezia Sympodialis Allergen Mala s 11 Induces Human Dendritic Cell Maturation, in Contrast to Its Human Homologue Manganese Superoxide Dismutase
- Author
-
Annika Scheynius, Monica Vilhelmsson, Reto Crameri, Arezou Zargari, Catharina Johansson, and Gunilla Jacobsson-Ekman
- Subjects
Antigens, Fungal ,Immunology ,Immunoglobulins ,Cross Reactions ,medicine.disease_cause ,Homology (biology) ,Microbiology ,Superoxide dismutase ,Allergen ,Antigens, CD ,medicine ,Humans ,Immunology and Allergy ,CD40 Antigens ,Antigen-presenting cell ,Cells, Cultured ,chemistry.chemical_classification ,Malassezia ,Membrane Glycoproteins ,integumentary system ,biology ,Superoxide Dismutase ,Dendritic Cells ,HLA-DR Antigens ,General Medicine ,Dendritic cell ,Allergens ,Flow Cytometry ,biology.organism_classification ,Recombinant Proteins ,Phenotype ,Enzyme ,chemistry ,Malassezia sympodialis ,B7-1 Antigen ,biology.protein ,Cytokines ,B7-2 Antigen - Abstract
Background: Recently, we identified a major Malassezia sympodialis allergen, Mala s 11, which displays a high degree of DNA sequence homology to human manganese superoxide dismutase (hMnSOD). In atopic eczema patients sensitized to M. sympodialis, hMnSOD can elicit eczematous reactions and positive skin prick tests, suggesting cross- reactivity to Mala s 11 based on molecular mimicry. The objective of the current study was to compare the influence of Mala s 11 and hMnSOD on human dendritic antigen-presenting cells. Methods: Monocyte-derived dendritic cells (MDDCs) from healthy blood donors were co-cultured with recombinant Mala s 11 (rMala s 11), recombinant hMnSOD (rhMnSOD), lipopolysaccharide or cultured in medium alone. Phenotypic changes were analysed using flow cytometry and allogeneic lymphocyte proliferation assays. Cytokine release into culture supernatants was investigated using cytometric bead array. Results: Whereas rhMnSOD did not affect the MDDC phenotype, rMala s 11 up-regulated the maturation marker CD83, the co-stimulatory molecules CD40, CD80, CD86 and HLA-DR to a similar extent as lipopolysaccharide. Furthermore, rMala s 11, but not rhMnSOD, induced significantly higher levels of TNF-α, IL-6, IL-8, IL-10 and IL-12p70 in the culture supernatants at 24 h in comparison with MDDCs cultured in medium alone. Finally, MDDCs pre-incubated with rMala s 11 induced a significantly higher proliferation of allogeneic CD14-depleted peripheral blood monocytes than MDDCs pre-incubated with rhMnSOD. Conclusion: Our results suggest that Mala s 11, but not hMnSOD, affects the immune response of healthy individuals through dendritic cell maturation and cytokine release. This indicates that dendritic cells possess the ability to distinguish between Mala s 11 and its human homologue MnSOD.
- Published
- 2007
44. Cross-Reactivity and 1.4-Å Crystal Structure of Malassezia sympodialis Thioredoxin (Mala s 13), a Member of a New Pan-Allergen Family
- Author
-
Leonardo Scapozza, Peter Schmid-Grendelmeier, Christa Meier, Andreas Limacher, Reto Crameri, Sabine Zeller, and Andreas G. Glaser
- Subjects
Adult ,Male ,animal structures ,Protein Conformation ,Molecular Sequence Data ,Immunology ,Sequence alignment ,Cross Reactions ,Crystallography, X-Ray ,medicine.disease_cause ,Cross-reactivity ,Fungal Proteins ,Thioredoxins ,Protein structure ,medicine ,Humans ,Immunology and Allergy ,Molecular replacement ,Amino Acid Sequence ,Cloning, Molecular ,Peptide sequence ,Antibodies, Fungal ,Malassezia ,biology ,Allergens ,Immunoglobulin E ,Middle Aged ,biology.organism_classification ,Recombinant Proteins ,Molecular mimicry ,Biochemistry ,Malassezia sympodialis ,Female ,Thioredoxin - Abstract
We have identified thioredoxins (Trx) of Malassezia sympodialis, a yeast involved in the pathogenesis of atopic eczema, and of Aspergillus fumigatus, a fungus involved in pulmonary complications, as novel IgE-binding proteins. We show that these Trx, including the human enzyme, represent cross-reactive structures recognized by serum IgE from individuals sensitized to M. sympodialis Trx. Moreover, all three proteins were able to elicit immediate-type allergic skin reactions in sensitized individuals, indicating a humoral immune response based on molecular mimicry. To analyze structural elements involved in these reactions, the three-dimensional structure of M. sympodialis Trx (Mala s 13) has been determined at 1.4-Å resolution by x-ray diffraction analysis. The structure was solved by molecular replacement and refined to a crystallographic R factor of 14.0% and a free R factor of 16.8% and shows the typical Trx fold. Mala s 13 shares 45% sequence identity with human Trx and superposition of the solved Mala s 13 structure with those of human Trx reveals a high similarity with a root mean square deviation of 1.11 Å for all Cα atoms. In a detailed analysis of the molecular surface in combination with sequence alignment, we identified conserved solvent-exposed amino acids scattered over the surface in both structures which cluster to patches, thus forming putative conformational B cell epitopes potentially involved in IgE-mediated cross- and autoreactivity.
- Published
- 2007
45. Differential cytokine induction by the human skin-associated autoallergen thioredoxin in sensitized patients with atopic dermatitis and healthy control subjects
- Author
-
Lennart M. Roesner, Annika Scheynius, Reto Crameri, Mattia Garbani, Thomas Werfel, Susanne Hradetzky, Annice Heratizadeh, and University of Zurich
- Subjects
medicine.medical_treatment ,Immunology ,Human skin ,610 Medicine & health ,Autoantigens ,Dermatitis, Atopic ,03 medical and health sciences ,0302 clinical medicine ,Thioredoxins ,10183 Swiss Institute of Allergy and Asthma Research ,Healthy control ,medicine ,Immunology and Allergy ,Humans ,030304 developmental biology ,0303 health sciences ,2403 Immunology ,business.industry ,Atopic dermatitis ,Allergens ,medicine.disease ,Cytokine ,Case-Control Studies ,2723 Immunology and Allergy ,Cytokines ,Thioredoxin ,business ,030215 immunology - Published
- 2015
46. Effect of Allergic Bronchopulmonary Aspergillosis on Lung Function in Children with Cystic Fibrosis
- Author
-
Richard Kraemer, Natascha Deloséa, Reto Crameri, Sabina Gallati, and Pietro Ballinari
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Adolescent ,Cystic Fibrosis ,Genotype ,Cystic Fibrosis Transmembrane Conductance Regulator ,Comorbidity ,Critical Care and Intensive Care Medicine ,Aspergillosis ,Sensitivity and Specificity ,Cystic fibrosis ,Pulmonary function testing ,Aspergillus fumigatus ,Fungal Proteins ,Intensive care ,medicine ,Humans ,Pseudomonas Infections ,Child ,Specific Airway Resistance ,Sensitization ,Retrospective Studies ,biology ,business.industry ,Aspergillosis, Allergic Bronchopulmonary ,Allergens ,Antigens, Plant ,respiratory system ,medicine.disease ,biology.organism_classification ,Respiratory Function Tests ,respiratory tract diseases ,Logistic Models ,medicine.anatomical_structure ,Chronic Disease ,Immunology ,Disease Progression ,Female ,Allergic bronchopulmonary aspergillosis ,business - Abstract
The relationship between sensitization to Aspergillus fumigatus and progression of pulmonary function is not yet established in cystic fibrosis (CF).We aimed to evaluate onset of A. fumigatus sensitization and development of allergic bronchopulmonary aspergillosis (ABPA), as well as to determine the physiologic factors of lung function influencing these mechanisms in CF.Serial annual lung function tests performed in 122 children with CF (62 males; 60 females; age: 6-18 yr) provided data pertaining to FRC measured by plethysmography, lung clearance index, volume of trapped gas, effective specific airway resistance, and forced expiratory indices (FEV1, FEF at 50% VC). Specific IgE to recombinant A. fumigatus allergens, rAspf1 and rAspf3, served as marker for sensitization, and to rAspf4 and rAspf6 as indications for a serologic ABPA, were clinically diagnosed (Nelson criteria). By linear mixed-effect model analysis, five patient groups, (1) not sensitized and free from Pseudomonas aeruginosa, (2) intermittently P. aeruginosa colonized, (3) chronically P. aeruginosa infected, (4) sensitized, and (5) with ABPA, were retrospectively evaluated.A. fumigatus sensitization was best reflected by increased rAspf1+3-specific IgE levels, whereas, in most patients, sensitization was preceded by P. aeruginosa infection. Patients with ABPA demonstrated the most severe progression in all lung function parameters, and FEF at 50% VC, volume of trapped gas, and effective specific airway resistance were the best predictors (p0.0001). However, regarding distinction between sensitization to A. fumigatus and development of ABPA in the course of CF, chronic P. aeruginosa infection has to be taken into account.Airway narrowing, gas trapping, and small airway disease are the major targets for functional derangement in ABPA.
- Published
- 2006
47. Sensitization to the Yeast Malassezia Sympodialis Is Specific for Extrinsic and Intrinsic Atopic Eczema
- Author
-
Sabine Flückiger, Catharina Johansson, Maria Tengvall Linder, Peter Schmid-Grendelmeier, Barbra Fischer Casagrande, Annika Scheynius, and Reto Crameri
- Subjects
Adult ,Hypersensitivity, Immediate ,Male ,Allergy ,Antigens, Fungal ,Adolescent ,Enzyme-Linked Immunosorbent Assay ,Dermatology ,Immunoglobulin E ,Biochemistry ,Peripheral blood mononuclear cell ,Dermatitis, Atopic ,Atopy ,medicine ,Dermatomycoses ,Humans ,Molecular Biology ,Antibodies, Fungal ,Sensitization ,Skin Tests ,Malassezia ,biology ,business.industry ,Cell Biology ,Atopic dermatitis ,Allergens ,Middle Aged ,Patch Tests ,biology.organism_classification ,medicine.disease ,Recombinant Proteins ,medicine.anatomical_structure ,Malassezia sympodialis ,Immunology ,biology.protein ,Female ,business - Abstract
The opportunistic yeast Malassezia sympodialis belongs to the normal cutaneous flora but can also cause IgE-mediated sensitization in patients suffering from atopic eczema (AE). We investigated 706 individuals by ImmunoCAPm70 and skin-prick tests with a crude M. sympodialis extract. In AE patients, we further performed skin prick tests, atopy patch tests, ELISA, and peripheral blood mononuclear cells proliferation assays with recombinant M. sympodialis allergens (rMala s 1 and 5–9). In 52/97 patients with AE-specific IgE against M. sympodialis was detectable. Almost no reactivity to M. sympodialis was seen in patients suffering from other allergic diseases (4/571) and no reactivity at all was seen in healthy controls (0/38). Skin tests showed variable recognition patterns against the different molecular structures with a predominant sensitization to rMala s 1, 5, 6, and 9, confirmed also by specific serum IgE to these allergens. Interestingly, IgE- and T-cell-mediated reactivity against M. sympodialis was also found in patients with the intrinsic form of AE. Thus, sensitization to M. sympodialis is specific for AE patients and occurs in both the extrinsic and intrinsic variant of eczema. Recombinant yeast allergens represent a useful tool to study molecular structures and differential sensitization patterns in the pathogenesis of AE.
- Published
- 2006
48. Allergy Diagnosis, Allergen Repertoires, and Their Implications for Allergen-Specific Immunotherapy
- Author
-
Reto Crameri
- Subjects
Vaccines ,Allergy ,Genetically engineered ,business.industry ,medicine.medical_treatment ,Immunology ,Specific immunotherapy ,Anaphylactic reactions ,Immunotherapy ,Allergens ,medicine.disease_cause ,medicine.disease ,Recombinant Proteins ,Allergen ,Desensitization, Immunologic ,Hypersensitivity ,medicine ,Humans ,Immunology and Allergy ,Th1 response ,business ,Skin Tests ,Desensitization (medicine) - Abstract
Immunotherapy for allergic diseases represents an important but largely unmet medical need. Conventional immunotherapy suffers from several breakdowns related to the quality of the extracts used, the risk of inducing anaphylactic reactions, and the extremely long treatment time. Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome using genetically engineered recombinant allergens. New therapeutic strategies based on recombinant technology include peptide-based vaccines, engineered hypoallergens with reduced IgE-binding properties, nucleotide-conjugated vaccines that promote Th1 responses, and the possibility of developing prophylactic allergen vaccines.
- Published
- 2006
49. Factors responsible for differences between asymptomatic subjects and patients presenting an IgE sensitization to allergens. A GA2LEN project
- Author
-
Rudolph Valenta, Marcus Maurer, Jean Bousquet, Carlos Lahoz, Jm Anto, M. van Hage, G. Passalacqua, Reto Crameri, Marc Daëron, Bénédicte Leynaert, W. J. Fokkens, R. van Ree, Claus Bachert, P Colombo, and P. J. Bousquet
- Subjects
Hypersensitivity, Immediate ,Allergy ,Rhinitis, Allergic, Perennial ,T-Lymphocytes ,Immunology ,Down-Regulation ,Basophil ,medicine.disease_cause ,Immunoglobulin E ,Asymptomatic ,Atopy ,Allergen ,medicine ,Immunology and Allergy ,media_common.cataloged_instance ,Humans ,European union ,Asthma ,media_common ,Polymorphism, Genetic ,Superantigens ,biology ,Bacteria ,business.industry ,Receptors, IgE ,Rhinitis, Allergic, Seasonal ,Allergens ,medicine.disease ,medicine.anatomical_structure ,biology.protein ,medicine.symptom ,business - Abstract
The synthesis of allergen-specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen-specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen-specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen-specific IgE or IgG, epitope-specificity of IgE and their degree of polyclonality (mono- vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (FcepsilonRI) and other factors regulating the activation of FcepsilonRI-bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are many unanswered important questions that need to be addressed in order to better understand how IgE sensitization translates into clinical allergy. The assessment of differences between the asymptomatic and symptomatic groups of subjects represent one of the scientific programs of Global Allergy and Asthma European Network funded by the European Union and the hypotheses underlying these differences are presented in this paper.
- Published
- 2006
50. Datamining Methodology for LC-MALDI-MS Based Peptide Profiling
- Author
-
Annette Appel, Harald Tammen, Jens Lamerz, Hans-Dieter Zucht, Valery Khamenia, Hartmut Selle, Carsten Schiller, and Reto Crameri
- Subjects
Proteomics ,Maldi ms ,Computer science ,Organic Chemistry ,Computational Biology ,General Medicine ,computer.software_genre ,Mass spectrometric ,Computer Science Applications ,ComputingMethodologies_PATTERNRECOGNITION ,Workflow ,General purpose ,Data Interpretation, Statistical ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Databases, Genetic ,Drug Discovery ,Animals ,Humans ,Profiling (information science) ,Data mining ,Peptides ,computer - Abstract
This report will provide a brief overview of the application of data mining in proteomic peptide profiling used for medical biomarker research. Mass spectrometry based profiling of peptides and proteins is frequently used to distinguish disease from non-disease groups and to monitor and predict drug effects. It has the promising potential to enter clinical laboratories as a general purpose diagnostic tool. Data mining methodologies support biomedical science to manage the vast data sets obtained from these instrumentations. Here we will review the typical workflow of peptide profiling, together with typical data mining methodology. Mass spectrometric experiments in peptidomics raise numerous questions in the fields of signal processing, statistics, experimental design and discriminant analysis.
- Published
- 2005
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.