Special Issue "Molecular and Cellular Advances in Atopic Diseases".

Atopic diseases, which currently affect around one billion people worldwide, are experiencing a rising prevalence [...].

Effects of enzymatic hydrolysis combined with pressured heating on tree nut allergenicity.

Hazelnut, pistachio and cashew are tree nuts with health benefits but also with allergenic properties being prevalent food allergens in Europe. The allergic characteristics of these tree nuts after processing combining heat, pressure and enzymatic digestion were analyzed through in vitro (Western blot and ELISA) and in vivo test (Prick-Prick). In the analyzed population, the patients sensitized to Cor a 8 (nsLTP) were predominant over those sensitized against hazelnut seed storage proteins (Sprot, Cor a 9 and 14), which displayed higher IgE reactivity. The protease E5 effectively hydrolyzed proteins from hazelnut and pistachio, while E7 was efficient for cashew protein hydrolysis. When combined with pressured heating (autoclave and Controlled Instantaneous Depressurization (DIC)), these proteases notably reduced the allergenic reactivity. The combination of DIC treatment before enzymatic digestion resulted in the most effective methodology to drastically reduce or indeed eliminate the allergenic capacity of tree nuts.

Meropenem allergy testing performed at the bedside of hospitalized patients labelled with a penicillin allergy.

BACKGROUND: Meropenem is a widely prescribed beta-lactam for hospitalized patients. There are few data on meropenem allergy assessments in inpatients with a reported history of penicillin allergy who require a treatment with meropenem. This can lead to the use of less effective second-line antibiotics that may increase antibiotic resistances. We aimed to evaluate the clinical outcomes of a meropenem allergy assessment in admitted patients with a reported history of penicillin allergy that required meropenem for the treatment of an acute infection. METHODS: A retrospective analysis was performed on 182 inpatients labelled with a penicillin-allergy who received meropenem after an allergy assessment. The allergy study was performed bedside if meropenem was required urgently. The study included skin prick tests (SPTs) followed by an intradermal skin test (IDT) to meropenem, and a meropenem drug challenge test (DCT). If a non-immediate reaction to a beta-lactam was suspected, it was initiated with patch tests. RESULTS: The median age of the patients was 59.7 years (range 28-95) and 80 (44%) were women. A total of 196 sets of diagnostic workups were performed, with 189 (96.4%) of them being tolerated. Only two patients had a positive meropenem IV DCT, both presenting a non-severe cutaneous reaction that completely resolved after treatment. CONCLUSIONS: This study evidenced that a bedside meropenem allergy assessment of hospitalized patients labelled with a 'penicillin allergy' who require a broad-spectrum antibiotic for empiric coverage is a safe and effective procedure, avoiding the use of second-line antimicrobial agents.

Recent advances in cellular and molecular mechanisms of IgE-mediated food allergy.

Food allergy is a public health issue the prevalence of which is steadily increasing. New discoveries have contributed to the understanding of the molecular and cellular mechanisms that lead to IgE-mediated food allergy. Novel scientific findings have defined roles for specific cell types, such as T follicular helper cells, in induction of high-affinity IgE by B cells. Also, not only mast cells and basophils contribute to food anaphylaxis, but also other cell types, such as neutrophils and macrophages. Elucidation of mechanisms involved in sensitization to food allergens through organs including the skin is key to deepening our understanding of the "dual exposure" hypothesis, which suggests that allergic sensitization is mainly acquired through inflamed skin while the oral route induces tolerance. This review considers the latest scientific knowledge about the molecular and cellular mechanisms of IgE-mediated food allergy. It reveals crucial components involved in the sensitization and elicitation phases and emerging approaches in anaphylaxis pathophysiology.

A compilation answering 50 questions on monkeypox virus and the current monkeypox outbreak.

The current monkeypox disease (MPX) outbreak constitutes a new threat and challenge for our society. With more than 55,000 confirmed cases in 103 countries, World Health Organization declared the ongoing MPX outbreak a Public Health Emergency of International Concern (PHEIC) on July 23, 2022. The current MPX outbreak is the largest, most widespread, and most serious since the diagnosis of the first case of MPX in 1970 in the Democratic Republic of the Congo (DRC), a country where MPX is an endemic disease. Throughout history, there have only been sporadic and self-limiting outbreaks of MPX outside Africa, with a total of 58 cases described from 2003 to 2021. This figure contrasts with the current outbreak of 2022, in which more than 55,000 cases have been confirmed in just 4 months. MPX is, in most cases, self-limiting; however, severe clinical manifestations and complications have been reported. Complications are usually related to the extent of virus exposure and patient health status, generally affecting children, pregnant women, and immunocompromised patients. The expansive nature of the current outbreak leaves many questions that the scientific community should investigate and answer in order to understand this phenomenon better and prevent new threats in the future. In this review, 50 questions regarding monkeypox virus (MPXV) and the current MPX outbreak were answered in order to provide the most updated scientific information and to explore the potential causes and consequences of this new health threat.

Dupilumab for Atopic Dermatitis-From Clinical Trials to Molecular and Cellular Mechanisms.

Dupilumab is a monoclonal antibody that represents the first approved targeted biological therapy for adults, adolescents, and children older than 6 years with moderate-to-severe atopic dermatitis (AD). Dupilumab binds the shared chain of the interleukin-4 and interleukin-13 receptor blocking the downstream signaling of these cytokines. The clinical improvements induced by dupilumab were associated with remission of the dysregulated immune mechanisms linked with AD. Dupilumab reversed the epidermal barrier defects and improved the global molecular signature of AD. This review seeks to provide an overview on the development of dupilumab as the first target-specific biological treatment for AD, with a description of the clinical trials that have been performed in different age groups, their outcomes, and reported adverse effects. Novel aspects of dupilumab treatment, as well as the current knowledge on the molecular and cellular mechanisms underlying the treatment of AD with dupilumab, are summarized and discussed.

Diversity of T cells in the skin: Novel insights.

T cells populate the skin to provide an effective immunosurveillance against external insults and to maintain tissue homeostasis. Most cutaneous T cells are αß T cells, however, γδ T cells also exist although in much lower frequency. Different subsets of αß T cells can be found in the skin, such as short-lived effector T cells, central memory T cells, effector memory T cells, and tissue-resident memory T cells. Their differential biology, function, and location provide an ample spectrum of immune responses in the skin. Foxp3+ memory regulatory T cells have a pivotal role in maintaining homeostasis in the skin and their dysregulation has been linked with different skin pathologies. The skin also contains populations of non-classical T cells, such as γδ T cells, NK T cells, and MR1-restricted T cells. Their role in skin homeostasis and response to pathogens has been well established in the past years, however, there is also growing evidence of their role in mediating allergic skin inflammation and promoting sensitization to allergens. In this review, we provide an updated overview on the different subsets of T cells that populate the skin with a specific focus on their role in allergic skin inflammation.

Allergenic Content of New Alimentary Pasta Made of Lentils Compared with Lentil Seeds and Analysis of the Impact of Boiling Processing.

There is growing interest in legumes such as lentil as healthy ingredients in gluten-free products. In that respect, foods based on lentils, like alimentary pasta, have been produced and successfully commercialized in recent years. Lentils are also known for inducing severe allergic reactions; however, it is currently unknown if novel alimentary pasta based on lentil retains the same allergenic potential as lentil seeds. In this study, the allergenic content of alimentary lentil pasta compared with lentil seeds was analyzed by immunoassays using sera from patients with allergic sensitization to lentil or with specific antibodies that recognize major lentil allergens. The effect of boiling processing was also analyzed. Results showed that alimentary lentil pasta has a significant allergenic content close to the general allergenic content observed for lentil seeds. Both alimentary lentil pasta and lentil seeds were similarly affected by boiling, with an important transfer of allergens from the food to the boiling water. This study shows that alimentary pasta made of lentils has a significant allergenic potential and highlights the necessity to analyze the allergenic content of new foods and novel ingredients introduced in traditional food products.

Novel alimentary pasta made of chickpeas has an important allergenic content that is altered by boiling in a different manner than chickpea seeds.

Alimentary pasta made of chickpeas has been recently introduced in the market. The novelty and presentation of this food can have a confounding effect on chickpea allergic patients and can pose a risk to them. The allergenic content of novel alimentary chickpea pasta in comparison with regular chickpea seeds has not been analyzed so far. Protein extracts were obtained, and the allergenic content was analyzed with sera from chickpea allergic patients and antibodies against major allergens by western blot, ELISA, dot blot, and cellular assays. Alimentary chickpea pasta showed an important content in IgE-binding proteins and chickpea allergens: 7S globulin, 2S albumin, LTP, and PR-10, similar to hydrated and boiled chickpea seeds. During boiling, more allergens from alimentary chickpea pasta were transferred to the boiling water than chickpea seeds. Novel alimentary chickpea pasta retains an important allergenic content which is affected by boiling by transferring allergens to the cooking water.

Dupilumab for Atopic Dermatitis-From Clinical Trials to Molecular and Cellular Mechanisms.

Dupilumab is a monoclonal antibody that represents the first approved targeted biological therapy for adults, adolescents, and children older than 6 years with moderate-to-severe atopic dermatitis (AD). Dupilumab binds the shared chain of the interleukin-4 and interleukin-13 receptor blocking the downstream signaling of these cytokines. The clinical improvements induced by dupilumab were associated with remission of the dysregulated immune mechanisms linked with AD. Dupilumab reversed the epidermal barrier defects and improved the global molecular signature of AD. This review seeks to provide an overview on the development of dupilumab as the first target-specific biological treatment for AD, with a description of the clinical trials that have been performed in different age groups, their outcomes, and reported adverse effects. Novel aspects of dupilumab treatment, as well as the current knowledge on the molecular and cellular mechanisms underlying the treatment of AD with dupilumab, are summarized and discussed.

Adverse rare events to vaccines for COVID-19: From hypersensitivity reactions to thrombosis and thrombocytopenia.

Vaccines for the prevention of coronavirus disease 2019 (COVID-19) started to be developed since the initiation of the COVID-19 pandemic. Up to now, four vaccines have been authorized by international agencies such as European Medicines Agency (EMA). Two are DNA vaccines (ChAdOx1 nCov-19 and Ad26.COV2.S) and two mRNA vaccines (BNT162b2 and mRNA-1273). The administration of the vaccines has been associated with a strong decrease in the infections by SARS-CoV-2 and deaths associated with it. However, in parallel to these results, some rare adverse events have also been described. In that sense, events of thrombosis, thrombocytopenia, and hemorrhage have been described in close temporal proximity to the administration of the DNA vaccines ChAdOx1 nCov-19 and Ad26.COV2.S, but also mRNA vaccines. Recent scientific reports have been released with updated information on the possible association of thrombotic thrombocytopenia and COVID-19 vaccines. On the other hand, since the initiation of the vaccination campaigns, adverse hypersensitivity reactions have been described after mRNA and DNA vaccines administration for COVID-19. Although globally these adverse events are rare, a high proportion of the world population will be exposed to these vaccines. For that reason, their safety and tolerance should be carefully considered. In this review, we provide an updated review of the last scientific findings that can explain the rare side effects that the vaccines for COVID-19 can produce.

IgE epitopes of Ara h 9, Jug r 3, and Pru p 3 in peanut-allergic individuals from Spain and the US.

Non-specific lipid transfer proteins (LTPs) are well studied allergens that can lead to severe reactions, but often cause oral allergy syndrome in the Mediterranean area and other European countries. However, studies focused on LTP reactivity in allergic individuals from the United States are lacking because they are not considered major allergens. The goal of this study is to determine if differences in immunoglobulin (Ig) E binding patterns to the peanut allergen Ara h 9 and two homologous LTPs (walnut Jug r 3 and peach Pru p 3) between the US and Spain contribute to differences observed in allergic reactivity. Synthetic overlapping 15-amino acid-long peptides offset by five amino acids from Ara h 9, Jug r 3, and Pru p 3 were synthesized, and the intact proteins were attached to microarray slides. Sera from 55 peanut-allergic individuals from the US were tested for IgE binding to the linear peptides and IgE binding to intact proteins using immunofluorescence. For comparison, sera from 17 peanut-allergic individuals from Spain were also tested. Similar IgE binding profiles for Ara h 9, Jug r 3, and Pru p 3 were identified between the US and Spain, with slight differences. Certain regions of the proteins, specifically helices 1 and 2 and the C-terminal coil, were recognized by the majority of the sera more often than other regions of the proteins. While serum IgE from peanut-allergic individuals in the US binds to peptides of Ara h 9 and its homologs, only IgE from the Spanish subjects bound to the intact LTPs. This study identifies Ara h 9, Jug r 3, and Pru p 3 linear epitopes that were previously unidentified using sera from peanut-allergic individuals from the US and Spain. Certain regions of the LTPs are recognized more often in US subjects, indicating that they represent conserved and possible cross-reactive regions. The location of the epitopes in 3D structure models of the LTPs may predict the location of potential conformational epitopes bound by a majority of the Spanish patient sera. These findings are potentially important for development of peptide or protein-targeting diagnostic and therapeutic tools for food allergy.

Characterization of Relevant Biomarkers for the Diagnosis of Food Allergies: An Overview of the 2S Albumin Family.

2S albumins are relevant and often major allergens from several tree nuts and seeds, affecting mainly children and young people. The present study aims to assess how the structural features of 2S albumins could affect their immunogenic capacity, which is essential to comprehend the role of these proteins in food allergy. For this purpose, twelve 2S albumins were isolated from their respective extracts by chromatographic methods and identified by MALDI-TOF mass-spectrometry. Their molecular and structural characterization was conducted by electrophoretic, spectroscopic and in silico methods, showing that these are small proteins that comprise a wide range of isoelectric points, displaying a general high structure stability to thermal treatment. Despite low amino acid sequence identity, these proteins share structural features, pointing conformational epitopes to explain cross-reactivity between them. Immunoblotting with allergic patients' sera revealed those possible correlations between evolutionarily distant 2S albumins from different sources. The availability of a well-characterized panel of 2S albumins from plant-derived sources allowed establishing correlations between their structural features and their allergenic potential, including their role in cross-reactivity processes.