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Immunotoxins appear as promising therapeutic molecules, alternative to allergen-specific-immunotherapy. In this work, we achieved the development of a protein chimera able to promote specific cell death on effector cells involved in the allergic reaction. Der p 1 allergen was chosen as cell-targeting domain and the powerful ribotoxin α-sarcin as the toxic moiety. The resultant construction, named proDerp1αS, was produced and purified from the yeast Pichia pastoris. Der p 1-protease activity and α-sarcin ribonucleolytic action were effectively conserved in proDerp1αS. Immunotoxin impact was assayed by using effector cells sensitized with house dust mite-allergic sera. Cell degranulation and death, triggered by proDerp1αS, was exclusively observed on Der p 1 sera sensitized-humRBL-2H3 cells, but not when treated with non-allergic sera. Most notably, equivalent IgE-binding and degranulation were observed with both proDerp1αS construct and native Der p 1 when using purified basophils from sensitized patients. However, proDerp1αS did not cause any cytotoxic effect on these cells, apparently due to its lack of internalization after their surface IgE-binding, showing the complex in vivo panorama governing allergic reactions. In conclusion, herein we present proDerp1αS as a proof of concept for a potential and alternative new designs of therapeutic tools for allergies. Development of new, and more specific, second-generation of immunotoxins following proDerp1αS, is further discussed.

JOURNAL ARTICLE; INTRODUCTION Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk as both local and systemic adverse reactions may occur especially in the initial stages of treatment. We compared the tolerance to three buildup protocols of VIT and analyzed risk factors associated with adverse reactions occurring in this phase. METHODS We enrolled 165 patients divided into three groups based on the buildup protocol used (3, 4, 9 weeks). Severity of systemic reactions was evaluated according to World Allergy Organization model. Results were analyzed using exploratory descriptive statistics and variables were compared using analysis of variance. RESULTS Fifty-three patients (32%) experienced some form of adverse reaction, 43 were local and 10 systemic. Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). Severity of local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the appearance of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association of severity of the local reaction with female gender. As for the risk factors associated with systemic reactions at buildup phase, we found no significant differences in these values depending on protocol used or the insect responsible. CONCLUSIONS The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied the 9-week schedule presented no systemic reactions, so it can be considered the safest protocol. Yes

Journal Article; Research Support, Non-U.S. Gov't; CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neutrophils and to endothelial cells. Allergen-specific immunotherapy is widely used to treat allergic diseases, and the molecular mechanisms underlying this therapy are poorly understood. The present work was undertaken to analyze A) the in vitro effect of allergens and immunotherapy on cell-surface CD66b expression of neutrophils from patients with allergic asthma and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b expression of neutrophils from nasal lavage fluid during the spring season. Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid as a general marker of neutrophil activation. RESULTS CD66b cell-surface expression is upregulated in vitro in response to allergens, and significantly reduced by immunotherapy (p

The study of cross-reactivity in allergy is key to both understanding. the allergic response of many patients and providing them with a rational treatment In the present study, protein microarrays and a co-sensitization graph approach were used in conjunction with an allergen microarray immunoassay. This enabled us to include a wide number of proteins and a large number of patients, and to study sensitization profiles among members of the LTP family. Fourteen LTPs from the most frequent plant food-induced allergies in the geographical area studied were printed into a microarray specifically designed for this research. 212 patients with fruit allergy and 117 food-tolerant pollen allergic subjects were recruited from seven regions of Spain with different pollen profiles, and their sera were tested with allergen microarray. This approach has proven itself to be a good tool to study cross-reactivity between members of LTP family, and could become a useful strategy to analyze other families of allergens. Yes

Jose Luis Justícia1, Eva Baró2, Victoria Cardona3, Pedro Guardia4, Pedro Ojeda5, José Maria Olaguíbel6, José Maria Vega7, Carmen Vidal81Medical Department, Stallergenes Ibérica, Barcelona, Spain; 2Health Outcomes Research Department, 3D Health Research, Barcelona, Spain; 3Hospital Vall d'Hebron, Barcelona, Spain; 4Hospital Virgen Macarena, Sevilla, Spain; 5Clínica de Asma y Alergia Dres. Ojeda, Madrid, Spain; 6Complejo Hospitalario de Navarra, Pamplona, Spain; 7Hospital Regional Universitario Carlos Haya Málaga, Spain; 8Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, SpainBackground: Allergen-specific immunotherapy (SIT) is a treatment capable of modifying the natural course of allergy, so ensuring good adherence to SIT is fundamental. Up until now there has not existed an instrument specifically developed to measure patient satisfaction with SIT, although its assessment could help us to comprehend better and improve treatment adherence and effectiveness. The aim of this study was to develop an instrument to measure adult patient satisfaction with SIT.Methods: Items were generated from a literature review, focus groups with allergic adult patients undergoing SIT, and a meeting with experts. Potential items were administered to allergic patients undergoing SIT in an observational, cross-sectional, multicenter study. Item reduction was based on quantitative and qualitative criteria. A preliminary assessment of feasibility, reliability, and validity of the retained items was performed.Results: An initial pool of 70 items was administered to 257 patients undergoing SIT. Fifty-four items were eliminated resulting in a provisional instrument with 16 items. Factor analysis yielded four factors that were identified as perceived efficacy, activities and environment, cost-benefit balance, and overall satisfaction, explaining 74.8% of variance. Ceiling and floor effects were negligible for overall score. Overall score was associated with the type and intensity of symptoms.Conclusion: This is the first attempt to develop a satisfaction with SIT measure from the perspective of the allergic patient, and evidence has been found in favor of its reliability and validity.Keywords: allergy, allergen-specific immunotherapy, questionnaire, scale, assessment, satisfaction

Journal Article; Research Support, Non-U.S. Gov't; An aeropalynological study was carried out in the atmosphere of Estepona, a very popular tourist resort situated in the "Costa del Sol", (southern Spain) based on the data obtained during a three year air-monitoring programme (March 1995 to March 1998) using a volumetric pollen trap. The 34 taxa that reached a 10-day mean air pollen concentration equal to or greater than 1 grain of pollen/m(3) of air are reflected in the calendar. The first 10 taxa, in order of abundance, were: Cupressaceae, Olea europaea, Quercus, Poaceae, Urticaceae, Plantago, Pinus, Chenopodiaceae-Amaranthaceae, Ericaceae and Castanea, the first 3 of which accounted for approximately 56 % of the annual total pollen count. The greatest diversity of pollen type occurred during spring, while the highest pollen concentrations were reached from February-June, when approximately more than 80 % of the annual total pollen was registered. The lowest concentrations were obtaining during January, August and September. The annual quantity of pollen collected, the intensity and the dates on which the maximum peaks were recorded differed for the 3 years studied, which can be explained by reference to various meteorological parameters, especially rainfall and temperature. The pollen calendar spectrum is typically Mediterranean and similar to those of nearby localities, in which many pollen types are represented and the long tails indicating long flowering periods. Yes