The value of the basophil activation test in the evaluation of patients reporting allergic reactions to the BNT162b2 mRNA COVID-19 vaccine

The present study has been supported by the Institute of Health ‘Carlos III’ (ISCIII) of the Ministry of Economy and Competitiveness (grants co-funded by European Regional Development Fund (ERDF): PI18/00095, RETICS ARADYAL RD16/0006/0001; Andalusian Regional Ministry Health (PE-0172- 2018). ML is supported by the ‘Río Hortega’ program [CM20/00210] from the ISCIII. CM holds a ‘Nicolas Monardes’ research contract (RC- 0004- 2021) and ID holds an SAS Stabilization contract (ref B-0001- 2017) by Andalusian Regional Ministry Health. Funding for open access charge: Universidad de Málaga / CBU

Hot topics in allergen immunotherapy, 2023: Current status and future perspective

The importance of allergen immunotherapy (AIT) is multifaceted, encompassing both clinical and quality‐of‐life improvements and cost‐effectiveness in the long term. Key mechanisms of allergen tolerance induced by AIT include changes in memory type allergen‐specific T‐ and B‐cell responses towards a regulatory phenotype with decreased Type 2 responses, suppression of allergen‐specific IgE and increased IgG$_{1}$ and IgG$_{4}$, decreased mast cell and eosinophil numbers in allergic tissues and increased activation thresholds. The potential of novel patient enrolment strategies for AIT is taking into account recent advances in biomarkers discoveries, molecular allergy diagnostics and mobile health applications contributing to a personalized approach enhancement that can increase AIT efficacy and compliance. Artificial intelligence can help manage and interpret complex and heterogeneous data, including big data from omics and non‐omics research, potentially predict disease subtypes, identify biomarkers and monitor patient responses to AIT. Novel AIT preparations, such as synthetic compounds, innovative carrier systems and adjuvants, are also of great promise. Advances in clinical trial models, including adaptive, complex and hybrid designs as well as real‐world evidence, allow more flexibility and cost reduction. The analyses of AIT cost‐effectiveness show a clear long‐term advantage compared to pharmacotherapy. Important research questions, such as defining clinical endpoints, biomarkers of patient selection and efficacy, mechanisms and the modulation of the placebo effect and alternatives to conventional field trials, including allergen exposure chamber studies are still to be elucidated. This review demonstrates that AIT is still in its growth phase and shows immense development prospects

Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein

The complement system is a key component of the innate immune response to viruses and proinflammatory events. Exaggerated complement activation has been attributed to the induction of a cytokine storm in severe SARS-CoV-2 infection. However, there is also an argument for the protective role of complement proteins, given their local synthesis or activation at the site of viral infection. This study investigated the complement activation-independent role of C1q and C4b-binding protein (C4BP) against SARS-CoV-2 infection. The interactions of C1q, its recombinant globular heads, and C4BP with the SARS-CoV-2 spike and receptor binding domain (RBD) were examined using direct ELISA. In addition, RT-qPCR was used to evaluate the modulatory effect of these complement proteins on the SARS-CoV-2-mediated immune response. Cell binding and luciferase-based viral entry assays were utilised to assess the effects of C1q, its recombinant globular heads, and C4BP on SARS-CoV-2 cell entry. C1q and C4BP bound directly to SARS-CoV-2 pseudotype particles via the RBD domain of the spike protein. C1q via its globular heads and C4BP were found to reduce binding as well as viral transduction of SARS-CoV-2 spike protein expressing lentiviral pseudotypes into transfected A549 cells expressing human ACE2 and TMPRSS2. Furthermore, the treatment of the SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes with C1q, its recombinant globular heads, or C4BP triggered a reduction in mRNA levels of proinflammatory cytokines and chemokines such as IL-1β, IL-8, IL-6, TNF-α, IFN-α, and RANTES (as well as NF-κB) in A549 cells expressing human ACE2 and TMPRSS2. In addition, C1q and C4BP treatment also reduced SARS-CoV-2 pseudotype infection-mediated NF-κB activation in A549 cells expressing human ACE2 and TMPRSS2. C1q and C4BP are synthesised primarily by hepatocytes; however, they are also produced by macrophages, and alveolar type II cells, respectively, locally at the pulmonary site. These findings support the notion that the locally produced C1q and C4BP can be protective against SARS-CoV-2 infection in a complement activation-independent manner, offering immune resistance by inhibiting virus binding to target host cells and attenuating the infection-associated inflammatory response

TEACHERS VIEWS OF THE NEW EDUCATIONAL ENVIRONMENT - THE ONE-COMPUTER CLASSROOM

Glavni je cilj provedenih istraživanja, empirijskog neeksperimentalnog u listopadu 2006. g., i kvalitativnog, provedenog metodom Delphi u travnju 2008. g., ispitivanje gledišta učitelja primarnog obrazovanja o uporabi jednog računala u razredu i o novoj obrazovnoj sredini Ñ učionici s jednim računalom. U rezultatima kvantitativnog istraživanja statistički je značajna na razini 1% varijabla posjedovanje računala u razredu, što znači da učitelji koji imaju računalo u razredu imaju pozitivnije gledište o njegovoj uporabi. Rezultati kvalitativnog istraživanja upozoravaju na potrebu prilagodbe obrazovnog sustava promijenjenom načinu življenja. Tradicionalni školski sustav nužno je transformirati u sustav novoga digitalnog doba, obilježenog inovacijama te nizom postupaka pretvorbe i redefinicije nastavnih programa koji su konzistentni s novim tehnologijama i pratećom multimedijom.The main goal of the empirical, non-experimental study conducted in October 2006, and of the qualitative study conducted by using the Delphi method in April 2008, was to examine the views of elementary-school teachers on the use of one computer in the classroom and on the new educational environment - the one-computer classroom. The results of the quantitative study show that the variable of having a computer in the classroom is statistically significant at the level of 1%, which means that teachers who have a computer in the classroom have a more positive view on its use. The results of the qualitative study indicate that there is a need to adjust the education system to a changed way of life. The traditional school system must be transformed into a new digital age system, marked by innovations and a number of processes of transforming and redefining teaching programmes to make them consistent with the new technologies and accompanying multimedia

Alpine altitude climate treatment for severe and uncontrolled asthma: an EAACI position paper

Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro-immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways

Vaccines and allergic reactions:The past, the current COVID-19 pandemic, and future perspectives

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.</p

Vaccines and allergic reactions:The past, the current COVID-19 pandemic, and future perspectives

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.</p

Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy

Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy

Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. From the Clinical Editor: Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.L.P., A.G.T., L.K., G.S. and U.K. thank Brunel University London for strategic Infrastructure funding. H.A.K. acknowledges the Deanship of Scientific Research at King Saud University for funding via Group No. RGP-009