No description available.

Yes / Background:To inform the development of the European Academy of Allergy and Clinical Immunology’s (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT. Methods:We performed a systematic review, which involved searching nine data-bases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses.Results:98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of 1.11 (95% CI 1.66, 0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD 1.21 (95% CI 1.87, 0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95% CI 0.23, 0.58), but one study showed a beneficial long-term effect. For secondary outcomes, subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen-specific airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR. AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported. The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective. Conclusions: AIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiveness and cost-effectiveness. / EAACI; BM4SIT. Grant Number: 601763; European Union's Seventh Framework Programme FP7

Regulatory T cells (Treg) are essential for the induction and maintenance of immunological tolerance to self and foreign antigens. The development of allergic asthma is mediated by T helper cell type-2 (Th2) inflammatory mechanisms and may also involve, based on murine and human studies of allergic asthma, compromised Treg immune regulation. Our overall objective was to more thoroughly elucidate the biology of Treg in allergic asthma, and to better understand their potential as a treatment for the disease. Initially, we characterized three different Treg phenotypes based on frequency and functional capacity. We showed both quantitative and functional heterogeneity in circulating Treg. Quantitative variability was also observed in circulating, but not airway, Treg when comparisons were made between healthy controls and asthmatic subjects. These findings emphasize the need for clear definitions of Treg phenotypes, and that interpretation of their frequency and function in health and disease needs to be phenotype-specific. Next, we assessed the Treg response in mild allergic asthmatic isolated early responders and dual responders after allergen inhalation challenge. We observed a reduced frequency of airway Treg after allergen challenge in DR, but not IER, associated with a smaller ratio of Treg to CD4+ cells. These data suggest that Treg to T effector cell (Teff) balance is important in the regulation of late asthmatic responses. Lastly, we evaluated the effects of two novel monoclonal anti-asthma therapies on circulating Treg after allergen inhalation challenge. We demonstrated that neither anti-OX40L nor anti-TSLP therapy altered circulating Treg frequency, while anti-TSLP, but not anti-OX40L, was effective in attenuating allergen-induced airway responses. These observations demonstrate the need for further investigation into the effects of anti-asthma therapies on Treg as well as the development of novel therapies aimed at manipulating Treg in order to better control immune responses. The findings of this thesis enhance our understanding of Treg in allergic asthma. Treg, utilized as stand-alone or adjunct therapy, may provide a novel therapy in the treatment of allergic asthma. / Thesis / Doctor of Philosophy (PhD)

No description available.

No description available.

Diese Arbeit beschreibt die immunologischen Eigenschaften von Acanthochilonema viteae Tropomyosin, einem Muskel-assoziierten Protein. A. viteae ist ein zu den Filarien gehörender Parasit von Gerbilen, ähnlich dem humanpathogenen Filarie Onchocercha volvulus. Diese Arbeit hatte die funktionelle Charakterisierung von A. viteae Tropomyosin im Kontext der natürlichen Infektion und experimentellen Vakzinierung zum Ziel. Das allergene Potential des Tropomyosins und die Produktion von spezifischen IgE-Antikörpern wurden untersucht. Außerdem wurden Tropomyosin-spezifische monoklonale Antikörpern (mAk) entwicklet. Es konnte gezeigt werden, dass Tropomyosin als vielversprechender Kandidat zur Vakzinentwicklung gegen Filariosen angesehen werden kann, wobei berücksichtigt werden muss, dass deutliche Effekte nur unter Th1-Bedingungen auftreten. Die Vakzinierung mit Protein oder DNA reduzierte Adultwurmzahlen um 30 bzw. 45%. Während einer Infektion fungiert Tropomyosin als funktionelles Allergen und führt zur Produktion von hohen Mengen spezifischen IgEs. Ein Screening synthetischer Peptid-Bibliotheken zeigte gemeinsame 13 IgG- und 11 IgE-Epitope. Weiters konnte Kreuzreaktivität mit anderen Tropomyosinen und diesen gemeinsamen IgE-Epitopen nachgewiesen werden. Mit Hilfe von mAk konnte gezeigt werden, dass Tropomyosin auf der Oberfläche der Kutikula der Larvenstadien L3 und microfilariae des Parasiten vorkommt. Durch die Deglykosylierung des nativen Proteins wurde deutlich, dass einige Epitope von posttranslationellen Modifikationen gebildet werden. Weitere Immunisierungen mit Tropomyosin führten zu einem ähnlichen Profil der Zellaktivierung und Antikörperproduktion wie der Adjuvant Aluminiumhydroxid. Jedoch führte die Behandlung zur IL-10 Produktion und zur Zunahme von Gr1+/ CD11b+ Zellpopulationen, welche natürliche Surpressors darstellen. Zusammenfassend kann gesagt werden, dass A. viteae Tropomyosin immunmodulierende Eigenschaften aufweist und als Komponente eines zu entwickelnden Vakzins in Frage kommt. / This study describes the immunological properties of Acanthocheilonema viteae muscle-associated protein tropomyosin. A. viteae is a filarial parasite of jirds that resembles the important human parasite Onchocerca volvulus. Focus of experiments is on unraveling the functional properties of tropomyosin in the context of an infection and experimental vaccination. Additionally, allergenic potential of tropomyosin was investigated and the ability to induce high levels of specific IgE. A part of the study was also aimed at the development of anti-tropomyosin monoclonal antibodies (mAb). This study revealed that tropomyosin is a promising antigen for vaccines against filarial nematodes, however, effective only in a Th1 biased environment. Vaccination with protein or DNA resulted in 30% - 45% protection that was not associated with specific IgG or IgE. During infection tropomyosin is an allergen and leads to the production of high levels of specific IgE. Screening of synthetic peptide libraries showed 13 IgG and 11 IgE co-located epitopes and revealed cross-reactivity with other tropomyosins and sharing of IgE epitopes. mAb were raised against A. viteae tropomyosin and showed that tropomyosin is abundant on the cuticle of L3 and microfilariae of the parasite. Deglycosylation of the native protein showed that some epitopes were formed by the posttranslational modifications. Additionally, immunization shows that tropomyosin induces a similar pattern of cell activation and antibody production as aluminium hydroxide adjuvant, but leads to the induction of IL-10 and the increase of population of GR1+/CD11b+ cells. These cells are regarded as natural suppressors. Taken together, results show that A. viteae tropomyosin has immunomodulating properties and can be considered as a component of an efficient vaccine.

L'allergie respiratoire au pollen de bouleau affecte un nombre important de personnes dans le monde. Il est estimé que 100 millions d'individus sont sensibilisés à l'allergène majeur du pollen de bouleau nommé Bet v 1. L’immunothérapie allergénique, basée sur l'administration répétée de l'allergène incriminé, permet la rééducation du système immunitaire du patient d’un profil TH2 vers un profil TH1/Treg et à terme la diminution des symptômes allergiques. Ces travaux de thèse avaient donc pour finalité de produire et de caractériser l'allergène recombinant Bet v 1, à des fins d’immunothérapie allergénique. Dans ce cadre, différentes méthodes analytiques ont été développées et appliquées afin d'optimiser le procédé de production via l'élimination de différentes impuretés liées au produit ou au procédé de production et de documenter la structure de l’allergène. En particulier, l'utilisation de la spectrométrie de masse a permis la détermination de la masse exacte de l'allergène ainsi que la vérification complète de sa séquence en acides aminés. Les travaux en spectrométrie de masse ont également contribué aux détections et identifications de diverses impuretés et produits de dégradations et ont ainsi conduit à plusieurs optimisations du procédé industriel de production de l'allergène recombinant. Les activités immunologiques de certains produits de dégradations ont également été investiguées. La structure tertiaire (spatiale) de l'allergène a été déterminée par diffraction aux rayons X. Enfin, ces travaux ont permis de documenter la qualité de l'allergène recombinant rBet v 1 afin i) de l'établir comme substance de référence pour la Pharmacopée Européenne et ii) de procéder à une étude clinique d’immunothérapie allergénique de phase II auprès de 483 patients allergiques au pollen de bouleau. / Respiratory allergy to birch pollen affects a large number of people in the world. It is estimated that 100 million people are sensitized to the major allergen from birch pollen, namely Bet v 1. Allergen immunotherapy, based on the repeated administration of the allergen of interest, allows the modification of the patient's immune response from a TH2 to a TH1/Treg pattern and thus the reduction of allergic symptoms. This study was therefore aimed to produce and characterize the recombinant Bet v 1 (rBet v 1) allergen, for immunotherapy purpose.In this context, various analytical methods have been developed and applied in order to optimize the production of rBet v 1 via the reduction of process or product-related impurities as well as to document the quality of the purified allergen. In particular, the use of mass spectrometry has allowed the determination of the exact mass of the intact allergen and the complete verification of its amino acid sequence. Mass spectrometry data have also contributed to the detection and identification of impurities and degradation products and have therefore led to several optimizations of the industrial process for the production of the recombinant allergen. Immunological activities of certain degradation products were also investigated and the allergen tertiary structure was determined by X-ray diffraction. Finally, this study was decisive in order i) to establish rBet v 1 as a chemical reference substance for the European Pharmacopoeia as well as ii) to perform a phase II clinical study conducted in 483 patients with birch pollen-induced rhinoconjunctivitis.

Background: Storage mites are frequently found in our daily environment. Nevertheless, storage mite allergy is often neglected in allergological diagnostics and possible allergies requiring therapy are thus overlooked. Methods: Recommendations for action are made based on a literature review from March 2021 to August 2021 in PubMed, Medline, and GoogleScholar. Results: This review article provides an overview of the species of storage mites, sensitization rates in different countries and occupations, and co-sensitization rates to house dust mite. Recommendations for diagnosis as well as therapy are given. The importance of provocation testing as well as causal therapy by allergen immunotherapy (AIT) is presented. Conclusion: The position paper gives recommendations for the diagnosis and therapy of allergic rhinitis in case of storage mite allergy. AIT is recommended in symptomatic allergy and proven storage mite allergy. Reliable detection by provocation testing is advised in this persistent allergy. The therapy should be carried out independently of the treatment of a possible house dust mite allergy.

Poverty and long distances are two reasons why some people in the third world countries hasdifficulties seeking medical help. A solution to the long distances could be if the medical carewas more mobile and diagnostically tests could be performed on site in villages. A new pointof-care test based on a small blood shows promising results both in run time and mobility.However, the method still needs more advanced equipment for analysis of the resultingmicroarray. This study has investigated the potential to perform the analysis within asmartphone application, performing all steps from image capturing to a diagnostic result. Theproject was approach in two steps, starting with implementation and selection of imageanalysis methods and finishing with implementing those results into an Android application.A final application was not developed, but the results gained from this project indicates that asmartphone processing power is enough to perform heavy image analysis within a sufficientamount of time. It also imply that the resolution in the evaluated images taken with a Nexus 6together with an external macro lens most likely is enough for the whole analysis, but furtherwork must be done to ensure it.

Introduktion: I Sverige har det uppmätts att 27% av befolkningen har en luftvägsallergi. Dessa behandlas främst med symtomlindrande läkemedel men när detta inte räcker till kan allergenspecifik immunterapi (ASIT) övervägas. Denna behandling kan ges antingen sublingualt eller med subkutana injektioner. Den första studien om ASIT publicerades 1911 och sedan dess har många studier gjorts angående dess effekter. Syfte: Syftet med studien var att undersöka patienters upplevelser av subkutan immunterapi (SCIT). De områden som belystes var upplevelsen av information och kommunikation, psykisk och fysisk påverkan av biverkningar samt hur behandlingen inverkar på vardagen. Metod: En kvalitativ studiedesign användes och data samlades in med hjälp av semistrukturerade intervjuer. Ett bekvämlighetsurval gjordes på en allergimottagning i Mellansverige och tio personer intervjuades. Resultat: Behandlingen påverkade somliga delar av vardagen i viss mån, till exempel att det är tidskrävande och att den fysiska aktiviteten blir begränsad under behandlingsdagen. En del biverkningar förekom, främst allmänna och lokala. Dessa hade viss påverkan på vardagen relaterat till exempelvis trötthet och koncentrationssvårigheter. Kontakten med mottagningen upplevdes positivt och informationen som erhölls inför behandlingsstart upplevdes som tillräcklig. Dock framkom att informationen kring allvarligare biverkningar inte nått fram till alla. Slutsats: Både de upplevda biverkningarna och behandlingen som helhet hade en viss påverkan på patienternas vardag. Kommunikationen och informationen från vården upplevdes överlag positivt. Vidare forskning inom området behövs för att kunna avgöra om dessa resultat är överförbara till en bredare population. / Introduction: It has been measured that 27% of the population in Sweden has a respiratory allergy. Primarily this is treated symptomatically with medication but in cases where this do not work, allergen specific immunotherapy (ASIT) can be considered. ASIT can be administered either sublingually or subcutaneously. The first study acknowledging ASIT was published in 1911 and since then many studies have been performed regarding its effects.      Aim: The aim of this study was to examine patients experiences of subcutaneous immunotherapy (SCIT). This included how patients experienced information and communication, how side-effects affected patients physically and psychologically and how the treatment affected the patients’ everyday life.  Methods: A qualitative study design was used and data was collected with semi-structured interviews. A convenience sample was made at an allergy reception in central Sweden and ten people were interviewed. Results: Parts of the patients’ everyday life were affected to some extent, for example because the treatment is time consuming and that the physical activity has to be limited during the same day as the injection is given. Some side-effects occurred, primarily general and local ones. These affected the everyday life in the sense that the patients felt tired and experienced difficulty concentrating. The contact with the reception was described in a positive manner and the information received before starting treatment was described to be enough. Although the information regarding serious side-effects had not been reached by everyone. Conclusion: Both the experienced side-effects and the treatment in its whole had a certain impact on the patients’ everyday life. The patients described the communication and the information in a positive way. More studies need to be performed in this field to be able to determine whether these results are transferable to a broader population.