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The first approved COVID-19 vaccines include Pfizer/BioNTech BNT162B2, Moderna mRNA-1273 and AstraZeneca recombinant adenoviral ChAdOx1-S. Soon after approval, severe allergic reactions to the mRNA-based vaccines that resolved after treatment were reported. Regulatory agencies from the European Union, Unites States and the United Kingdom agree that vaccinations are contraindicated only when there is an allergy to one of the vaccine components or if there was a severe allergic reaction to the first dose. This position paper of the European Academy of Allergy and Clinical Immunology (EAACI) agrees with these recommendations and clarifies that there is no contraindication to administer these vaccines to allergic patients who do not have a history of an allergic reaction to any of the vaccine components. Importantly, as is the case for any medication, anaphylaxis may occur after vaccination in the absence of a history of allergic disease. Therefore, we provide a simplified algorithm of prevention, diagnosis and treatment of severe allergic reactions and a list of recommended medications and equipment for vaccine centres. We also describe potentially allergenic/immunogenic components of the approved vaccines and propose a workup to identify the responsible allergen. Close collaboration between academia, regulatory agencies and vaccine producers will facilitate approaches for patients at risks, such as incremental dosing of the second injection or desensitization. Finally, we identify unmet research needs and propose a concerted international roadmap towards precision diagnosis and management to minimize the risk of allergic reactions to COVID-19 vaccines and to facilitate their broader and safer use.

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.

Children with severe asthma continue to experience symptoms despite long-term treatment with high doses of corticosteroids. Moreover, the heterogeneous nature of asthma and the presence of several phenotypes have limited our ability to develop an optimized management strategy for these patients. Adequate management of severe asthma in children necessitates a detailed understanding of what makes asthma difficult to control, knowledge of the causal factors, review of diagnosis for accurate identification of pediatric patients with severe asthma and a precise definition of the phenotypes to be able to better target the therapy. Advancement in all these aspects is likely to improve childhood asthma treatment in the future. Although our understanding of severe pediatric asthma has grown in recent years, there remains a lack of consensus and clarity around critical aspects of this condition. This review attempts to present a harmonized view on the definition of severe asthma in the pediatric age group, identification of phenotypes and diagnosis, the inflammatory cascade, pharmacological and non-pharmacological treatment strategies, considerations for follow-up and referral to specialists, and disease prevention strategies.

Advancing our understanding of mechanisms of immune regulation in allergy asthma autoimmune diseases tumor development organ transplantation and chronic infections could lead to effective and targeted therapies. Subsets of immune and inflammatory cells interact via ILs and IFNs; reciprocal regulation and counter balance among T H and regulatory T cells as well as subsets of B cells offer opportunities for immune interventions. Here we review current knowledge about ILs 1 to 37 and IFN gamma. Our understanding of the effects of ILs has greatly increased since the discoveries of monocyte IL (called IL 1) and lymphocyte IL (called IL 2); more than 40 cytokines are now designated as ILs. Studies of transgenic or knockout 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 important information about IL and IFN functions. We discuss their signaling pathways cellular sources targets roles in immune regulation and cellular networks roles in allergy and asthma and roles in defense against infections. (J Allergy Clin Immunol 2011;127:701 21.)

BACKGROUND: Tonsils are strategically located in the gateway of both alimentary and respiratory tracts representing the first contact point of food and aeroallergens with the immune system. Tonsillectomy removes only the palatine tonsils and sometimes adenoids. Lingual tonsil is anatomically big and remains lifelong intact. OBJECTIVE: The aim of this study was to demonstrate cellular and molecular mechanisms of oral tolerance induction to food and aeroallergens in human tonsils. METHODS: Tonsil allergen specific FOXP3(+) regulatory T (Treg) cells plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells were characterized by flow cytometry and suppressive assays. Intracellular staining [(3)H] thymidine incorporation and carboxy fluorescein succinimidyl ester dilution experiments were performed. Tonsil biopsies were analyzed by confocal microscopy. RESULTS: CD4(+)FOXP3(+) Treg cells and pDCs constitute important T and dendritic cell compartments in palatine and lingual tonsils. Tonsil pDCs have the ability to generate functional CD4(+)CD25(+)CD127( )FOXP3(+) Treg cells with suppressive property from naive T cells. CD4(+)FOXP3(+) Treg cells proliferate and colocalize with pDCs in vivo in T cell areas of lingual and palatine tonsils. Tonsil T cells did not proliferate to common food and aeroallergens. Depletion of FOXP3(+) Treg cells enables the allergen induced proliferation of tonsil T cells indicating an active role of Treg cells in allergen specific T cell unresponsiveness. High numbers of major birch pollen allergen Bet v 1 specific CD4(+)FOXP3(+) Treg cells are identified in human tonsils compared with peripheral blood. A positive correlation between the percentages of FOXP3(+) Treg cells and pDCs is observed in tonsils from nonatopic individuals. CONCLUSION: Functional allergen specific Treg cells are identified both in lingual and in palatine tonsils.

This paper is a characterization of the chestnut stand biotopes in Andalucia (Spain). The distribution of these stands is quite iregular, with four areas of chestnut tree dominant presence, located in Granada, Huelva, Malaga y Sevilla respectively, totalling over 9.000 ha. In these locations, 23 forest sites have been evaluated by computing a set of 34 phytoecological parameters and 7 silvicultural parameters. The sampling design was based on the Spanish Forest Map (Ceballos, 1966) overlaid on the Biogeoclimatic Classification of the Peninsular and Balearic Spain (Elena, 1996).This information has made it possible to establish the physioclimatic and edaphic habitat of the chestnut stands in Andalucia and to characterize their current silvicultural situation. As result, chestnut forest sites in Andalucia show the following features:1. Chestnut woodstands display strong heterogeneity, as a result of their human use, with four areas of discontinuous presence, absence of forestry uniformity and very different conservation and stability conditions.2. The most restrictive parameters in the chestnut stand biotopes have turned out being those retaled to thermic conditions (over 15 _C of anual temperature average) and to the soil reaction (moderately acid in all the cases).3. Chestnut stands occupy heterogeneous biotopes, with a high elevation range, marked summer aridity conditions and very varied edaphic textures that produce highly different conditions of permeability, soil water holding capacity and edaphoclimatic behaviour.4. The analysed soils are mainly classified as Cambisols and Luvisols, with predominant dystric and chromic units. Este trabajo presenta una caracterización paramétrica de los biotopos ocupados en la actualidad por formaciones de Castanea sativa Miller en la Comunidad Autónoma de Andalucía. A tal fin, se han evaluado un total de 23 localizaciones mediante la elaboración de 34 parámetros del biotopo de trascendencia fito-ecológica, junto con 7 más que caracterizan selvícolamente los castañares inventariados. La interpretación de esta información ha permitido la determinación de los hábitat fisioclimático y edáfico, central y marginal, del castaño en la región andaluza, así como la caracterización de la actual situación selvícola de sus masas. Los castañares andaluces presentan una elevada heterogeneidad tanto en los biotopos en los que se asientan como en el uso y manejo a los que se ven sometidos. El rango altitudinal de variación es superior a 1.000 m, si bien esto no se traduce en una heterogeneidad térmica –la temperatura media anual oscila ligeramente sobre los 15 _ C–. Con una precipitación media anual próxima a 900 mm, las condiciones de aridez estival son patentes, extendiéndose en todas las localizaciones estudiadas a lo largo de más de tres meses. Los suelos, mayoritariamente Cambisoles y Luvisoles, presentan reacción moderadamente ácida, con una composición textural variada que deriva en comportamientos físicos y edafoclimáticos muy dispares. El diferente uso y estado de conservación de los castañares analizados lleva a una elevada heterogeneidad selvícola y dasométrica. Las mejores masas aparecen en Aracena (Huelva), mientras que, en el otro extremo, presentan clara recesión las masas ubicadas en el entorno de Sierra Nevada (Granada).

In this paper, we have established the physiographic, climatic and soil optimum and marginal habitat parameters of Castanea sativa stands in the regions of Castilla y León, Castilla-La Mancha and Madrid (Spain). Chestnut stands are usually located between 620 m and 1100 m elevation showing a wide range of variation in their rainfall, in contrast to the narrow range of temperature variation. The soils of the chestnut stands studied are mainly Cambisols, Luvisols and Umbrisols, generally highly acid, loamy or sandy-loamy and having a low C/N ratio. We have also established the interpretation criteria for ranges of the marginal habitats in relation to the optimum ones, in order to evaluate the chances of risk if the introduction of this species was carried out in an area such as the one considered in our study. Thus, the greater risk/danger would be encountered on soils whose autumn rainfall parameters are lower than 220 mm, fine earth below 16,7 %, lime lower than 20.4 %, water holding capacity lower than 38 mm, top soil organic matter lower than 2.1 %, temperature oscillations over 18.5ºC and permeability higher than 4,7. The silvicultural parameter which best describes the forestry characteristics of the Castilian chestnut stands in relation to the biotope evaluation parameters is Hart's index per number of stools, which can be satisfactorily estimated by considering slope, winter rainfall, surpluses and soil permeability En el presente trabajo se han establecido los valores de los hábitats centrales y marginales de la fisiografía, edafología y climatología de las masas de Castanea sativa Miller en las comunidades autónomas de Castilla y León, Castilla-La Mancha y Madrid. Se ha podido comprobar al respecto que los castañares se suelen encontrar entre los 620 y los 1.100 m de altitud, presentan una amplia variación en su régimen pluviométrico, no así en el termométrico. Los suelos de los castañares estudiados son fundamentalmente Cambisoles, Luvisoles y Umbrisoles, generalmente fuertemente ácidos, francos o franco-arenosos y con baja relación C/N. También se establecen los criterios para interpretar los rangos de las hábitats marginales respecto de los centrales a fin de poder realizar una valoración del riesgo de efectuar la implantación de esta especie en un terreno del ámbito estudiado. El mayor riesgo se encontraría en terrenos cuyos parámetros de precipitaciones otoñales fueran inferiores a 220 mm, tierra fina inferior a 16,7 %, limo menor de 20,4 %, capacidad de retención de agua inferior a 38 mm, materia orgáncia superficial menor del 2,1 %, oscilación térmica mayor de 18,5 C y permeabilidad superior a 4,75. El parámetro selvícola que mejor describe las características dasonómicas del conjunto de los castañares castellanos en relación con los parámetros evaluadores del biotopo es el índice de Hart por número de cepas, el cual puede ser estimado con bastante aproximación en función de la pendiente del terreno, la precipitación de invierno, la suma de superávit y la permeabilidad del suelo.

Background The vitamin D metabolite 125(OH)2D3 (VitD3) is a potent immunosuppressive drug and among others is used for topical treatment of psoriasis. A proposed mechanism of VitD3 mediated suppression is priming of dendritic cells (DCs) to induce regulatory T (Treg) cells. Objective Currently there is confusion about the phenotype of VitD3 induced Treg cells and the DC derived molecules driving their development. We investigated Treg cell induction after VitD3 priming of 2 distinct skin DC subsets: Langerhans cells (LCs) and dermal dendritic cells (DDCs). Methods LCs and DDCs primed with VitD3 were cocultured with allogeneic naive T cells. The phenotype and function of the DCs and induced T cells were analyzed. Results Both VitD3 primed DC subtypes induced T cells with regulatory activity. Unexpectedly whereas the Treg cell populations generated by VitD3 primed LCs were CD25hiCD127lo forkhead box protein 3 (Foxp3)–positive cells which meet the criteria of classical inducible Treg cells the T cells developing in response to VitD3 primed DDCs were Foxp3- TR1 cells expressing IL 10. Inhibition experiments revealed that LC derived TGF ß is a key factor in the induction of Foxp3+ Treg cells whereas DDC derived IL 10 is important for the induction of IL 10+ TR1 cells. Conclusion Thus we report the novel finding that distinct but closely related DC subsets are differentially programmed by VitD3 to support development of either TGF ß–dependent Foxp3+ Treg cells or IL 10–dependent IL 10+ Treg cells.

Olive pollen has a complex allergenic profile, from which more than 10 allergens have been identified and characterized. Some of these belong to well-known protein families and others cannot be included in reported biochemical types. Most of these allergens have been produced by recombinant technology, mainly in Escherichia coli or in Pichia pastoris, and they are good candidates for diagnostic and therapeutic purposes. Diagnosis and immunotherapy of allergy currently use extracts prepared from homogenates of natural sources, which only allow us to detect sensitivity to the complete source. These extracts can be successfully replaced by mixtures with controlled amounts of specific allergenic proteins obtained by recombinant technology in order to define the sensitization profile of individual patients. Recombinant Ole e 1 can be used as a marker for sensitization to Oleaceae. Recombinants Ole e 2 (profilin) and Ole e 3 (polcalcin) can serve as markers of polysensitivity. Finally, recombinant forms of Ole e 6, Ole e 10, and the carboxy-terminal and amino-terminal domains of Ole e 9 would help to detect sensitization to these minority allergens that could be overlooked in the complete olive pollen extract. These recombinant molecules can help provide an accurate diagnosis of sensitivity to individual allergens and, therefore, improve the design of more efficacious allergen-based immunotherapy strategies.

'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.