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T cells populate the skin to provide an effective immunosurveillance against external insults and to maintain tissue homeostasis. Most cutaneous T cells are αβ T cells, however, γδ T cells also exist although in much lower frequency. Different subsets of αβ 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.

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.

Allergo journal international 30(5), 155-168 (2021). doi:10.1007/s40629-021-00178-2, Published by Urban & Vogel, München

Following the emergency use authorization of the vaccine mRNA-1273 on 18th December 2020 in the US and the vaccine BNT162b2 one week earlier, two mRNA vaccines are in currently used for the prevention of coronavirus disease 2019 (COVID-19). Phase 3 pivotal trials on both vaccines excluded individuals with a history of allergy to vaccine components. Immediately after the initiation of vaccination in the United Kingdom, Canada, and in the US, anaphylactic reactions have been reported. While the culprit trigger requires investigation, initial reports suggested the excipient polyethylene glycol 2000 (PEG-2000), which is contained in both vaccines as PEG-micellar carrier system as the potential culprit. Surface PEG chains form a hydrate shell to increase stability and prevent opsonization. Allergic reactions to such PEG-ylated lipids are rarely IgE-mediated, but may result from complement activation-related pseudoallergy (CARPA) that has been described to similar liposomes. In addition, mRNA-1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to e.g. gadolinium-based or iodinated contrast media. Skin prick-, intradermal-, epicutaneous- tests, in vitro sIgE assessment, evaluation of sIgG/IgM, as well as basophil activation test are in use to demonstrate allergic reactions to various components of the vaccines.

Hintergrund: Zur vorbeugenden Behandlung von COVID-19 (Coronaviruserkrankung 2019) wurden in einer beispiellosen weltweiten Forschungsanstrengung Sicherheit und Wirksamkeit neuer Impfstoffplattformen studiert, die noch nie zuvor am Menschen eingesetzt wurden. Weniger als ein Jahr nach der Entdeckung der SARS-CoV-2-Virussequenz (SARS-CoV-2, "severe acute respiratory syndrome coronavirus type 2") wurden diese in zahlreichen Landern fur den Einsatz zugelassen und es wurde mit Massenimpfungen begonnen. Die bislang in der Europaischen Union (EU) zugelassenen mRNA-Impfstoffe (mRNA, "messenger"-RNA) gegen SARS-CoV-2 BNT162b2 und mRNA-1273 basieren auf einer ahnlichen lipidbasierten Nanopartikeltragertechnologie; die Lipidkomponenten unterscheiden sich jedoch. Schwere allergische Reaktionen und Anaphylaxien nach COVID-19-Impfungen sind sehr seltene unerwunschte Nebenwirkungen, die aber aufgrund potenziell letaler Ausgange viel Aufmerksamkeit erhalten und ein hohes Mas an Verunsicherung ausgelost haben. Methoden: Das aktuelle Wissen zu anaphylaktischen Reaktionen auf Impfstoffe und speziell zu den derzeit neuen mRNA-COVID-19-Impfstoffen wurde zusammengestellt mittels einer Literaturanalyse durch Recherchen in Medline, Pubmed sowie den nationalen und internationalen Studien- und Leitlinienregistern, der Cochrane Library und dem Internet unter besonderer Berucksichtigung offizieller Webseiten der World Health Oranization (WHO), der Centers for Disease Control and Prevention (CDC), der European Medicines Agency (EMA), des Robert-Koch-Instituts (RKI) und des Paul-Ehrlich-Instituts (PEI). Ergebnisse: Basierend auf der internationalen Literatur und bisheriger Erfahrungen zu schweren allergischen Reaktionen im Kontext der COVID-19-Impfungen werden von einem Expertengremium Empfehlungen fur Prophylaxe, Diagnostik und Therapie dieser allergischen Reaktionen gegeben. Schlussfolgerung: Vor einer COVID-19-Impfung mit den derzeit zugelassenen Impfstoffen sind Allergietests fur die allermeisten Allergiker nicht notwendig. Bei allergischer/anaphylaktischer Reaktion auf den verabreichten COVID-19-Impfstoff wird eine allergologische Abklarung empfohlen, wie auch fur eine kleine potenzielle Risikopopulation vor der ersten Impfung. Die Evaluierung und Zulassung von Testverfahren sollten hierfur erfolgen. Zitierweise: Klimek L, Bergmann K-C, Brehler R, Pfutzner W, Zuberbier T, Hartmann K, Jakob T, Novak N, Ring J, Merk H; Hamelmann E, Ankermann T, Schmidt S, Untersmayr E, Hotzenecker W, Jensen-Jarolim E, Brockow K, Mahler V, Worm M. Practical Handling of Allergic Reactions to COVID-19 vaccines. A Position Paper from German and Austrian Allergy Societies AeDA, DGAKI, GPA and OGAI. Allergo J Int 2021;30:79-95 https: //doi.org/10.1007/s40629-021-00165-7

Herpes simplex virus type 1 (HSV-1) can induce in certain individuals with atopic dermatitis (AD) severe cutaneous infections that can spread throughout the entire body, a condition named as AD complicated by eczema herpeticum (ADEH). It has been recently found that ADEH patients can produce specific IgE against HSV-1 proteins, which may contribute to lower protection against HSV-1. However, little is known about the capacity of these HSV-1 proteins to produce an inflammatory response at the skin level. In this study, using a mouse model of AD-like dermatitis, three HSV-1 proteins (glycoprotein D -gD-, glycoprotein B -gB- and VP22) were applied on tape-stripped back skin mice in three exposures periods. Ovalbumin (OVA) and 0.9% NaCl were used as positive and negative controls, respectively. Skin samples were obtained for analysis of specific cell components of skin infiltration. The results showed that the viral protein gD induced a statistically significant increase in the number of dermal infiltrating CD3+, CD4+ cells and mast cells compared with the negative control group. gD was also able to induce epidermal thickening and epidermal infiltration of T cells closely related to the one produced in mice sensitized with OVA. However, VP22 and gB contributed to a lesser extent to skin inflammation. These results showed that proteins from HSV-1, especially gD, can have per se an important T cell and mast cell-driven inflammatory potential at the skin level.

Zwei Mitarbeiter des National Health Service (NHS) in England entwickelten nach der Verabreichung des BNT162b2-Impfstoffs von BionNTech gegen COVID-19 schwere allergische Reaktionen. Die britische Fachinformation fur den BNT162b2-Impfstoff enthalt bereits Hinweise auf eine Kontraindikation zur Anwendung bei Personen, die allergisch auf den Impfstoff oder einen seiner Bestandteile reagiert haben. Als Vorsichtsmasnahme hat die englische Regulationsbehorde fur Arzneimittel und Gesundheitsprodukte (MHRA) eine vorlaufige Anleitung herausgegeben, "Patienten mit schweren Allergien" grundsatzlich nicht zu impfen. Allergische Reaktionen auf Impfstoffe sind sehr selten, aber Impfstoffkomponenten verursachen bekanntermasen allergische Reaktionen. BNT162b2 ist ein Impfstoff, der auf einer in Lipidnanopartikel eingebetteten mRNA basiert und mit weiteren Substanzen angereichert wird, um den Transport in die Zellen zu ermoglichen. In der zentralen klinischen Phase-III-Studie wurde der BNT162b2-Impfstoff im Allgemeinen gut vertragen. Impfstoffe gelten als eine der wirksamsten Masnahmen im Bereich der offentlichen Gesundheit. Schwere allergische Reaktionen auf Impfstoffe sind selten, konnen jedoch lebensbedrohlich sein. Es ist ratsam, die Impfteams auf diese Gefahr aufmerksam zu machen und angemessene Vorsichtsmasnahmen zu treffen, wahrend mehr Erfahrungen mit dem neuen Impfstoff gesammelt werden.

Background After the beginning and during the worldwide pandemic caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), patients with allergic and atopic diseases have felt and still feel insecure. Currently, four vaccines against SARS-CoV-2 have been approved by the Paul Ehrlich Institute in Germany, and vaccination campaigns have been started nationwide. In this respect, it is of utmost importance to give recommendations on possible immunological interactions and potential risks of immunomodulatory substances (monoclonal antibodies, biologicals) during concurrent vaccination with the approved vaccines. Materials and methods This position paper provides specific recommendations on the use of immunomodulatory drugs in the context of concurrent SARS-CoV-2 vaccinations based on current literature. Results The recommendations are covering the following conditions in which biologicals are indicated and approved: 1) chronic inflammatory skin diseases (atopic dermatitis, chronic spontaneous urticaria), 2) bronchial asthma, and 3) chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with atopic dermatitis or chronic spontaneous urticaria are not at increased risk for allergic reactions after COVID-19 vaccination. Nevertheless, vaccination may result in transient eczema exacerbation due to general immune stimulation. Vaccination in patients receiving systemic therapy with biologicals can be performed. Patients with severe asthma and concomitant treatment with biologicals also do not have an increased risk of allergic reaction following COVID-19 vaccination which is recommended in these patients. Patients with CRSwNP are also not known to be at increased risk for allergic vaccine reactions, and continuation or initiation of a treatment with biologicals is also recommended with concurrent COVID-19 vaccination. In general, COVID-19 vaccination should be given within the interval between two applications of the respective biological, that is, with a time-lag of at least 1 week after the previous or at least 1 week before the next biological treatment planned. Conclusion Biologicals for the treatment of atopic dermatitis, chronic spontaneous urticaria, bronchial asthma, and CRSwNP should be continued during the current COVID-19 vaccination campaigns. However, the intervals of biological treatment may need to be slightly adjusted (DGAKI/AeDA recommendations as of March 22, 2021).

The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate that human sperm–oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm toward the source of a chemoattractant and hence to the oocyte. Chemokines represent a superfamily of small (8–11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm–oocyte interaction.Graphical AbstractSummary SentenceThe chemokine CCL20 is produced by human oocytes as well as surrounding cumulus granulosa cells and induces chemotaxis of CCR6+ sperm. Infertile male donors demonstrate increased levels of CCL20 in testis and seminal fluid, which may negatively influence sperm–oocyte interaction.

Background: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, with an increasing incidence in clinical practice. AD models have demonstrated that TGF-β signaling is compromised in regulatory T cells (Tregs). Objectives: This study aimed to investigate the TGF-β-dependent in vitro conversion of CD4+CD25– T cells derived from AD-patients into CD4+CD25+Foxp3+ induced Tregs (iTregs) in comparison to healthy controls. Methods: To analyze in vitro iTreg conversion, human CD4+CD25– T cells were cultured on anti-CD3-coated plates in the presence of TGF-β and IL-2 for up to 3 days. Consequently, the underlying mechanism of impaired CD4+CD25+Foxp3+ iTreg generation was explored by focusing on TGF-β signaling. Finally, the functionality of iTregs was investigated. Results: Conversion of CD4+CD25–Foxp3– into CD4+CD25+Foxp3+ iTregs was diminished in AD individuals. Impaired iTreg generation was accompanied by a reduced surface expression of GARP (glycoprotein A repetitions predominant), a marker for activated Tregs. A reduced expression of Smad3 mRNA was revealed in CD4+CD25– T cells. Interestingly, the suppressive quality of iTregs was found to be equal in cells derived from AD and healthy donors. Conclusion: The signaling effect of TGF-β receptors on the suppressor quality of iTreg conversion is conserved. Impaired iTreg generation might be a reason for the lack of immune suppression in AD patients and contributes to the chronicity of the disease.

V članku so predstavljene posebnosti fotografij, posnetih s pametnimi telefoni in njihov potencial za zbiranje prostovoljnih geografskih informacij. Ločljivost in jasnost fotografij, posnetih s pametnim telefonom, je danes že enakovredna fotografijam posnetih s kompaktnimi digitalnimi fotoaparati, hkrati pa omogočajo sprotno shranjevanje lokacije fotografiranja. Na primeru obdelave posamezne fotografije s pomočjo interaktivne orientacije, so te prednosti ovrednotene z vidika njihovega potenciala za fotogrametrični zajem, ob ažuriranju topografskih kart. Kljub dobrim potencialom, pa na koncu obseg zornega polja fotografije odloča o tem ali bomo iz take fotografije lahko izmerili merske 3R-prostorske podatke. The potential of smartphone images for measuring volunteered geographic information.This article presents the characteristics of smartphone images and their potential for collecting the volunteered geographic information. Today the smartphone image quality is equivalent to those taken with compact digital cameras, and they allow the real-time storage of the location from where the image was taken. Taking the example of processing a single image by using interactive orientation, these advantages are evaluatedin terms of their potential for photogrammetric measurements when updating topographic maps. Despitethe promising potential, the field of view extent of an image ultimately determines whether we will be ableto extract metric spatial 3D data from such an image.

The excipient polyethylene glycol (PEG) contained in the mRNA vaccines for COVID-19 has been pointed out as one of the possible triggers of the hypersensitivity reactions that have been described since the beginning of the vaccine campaigns for COVID-19 protection.1 However, PEG is not present in the mRNA vaccines in an isolated form but in conjugation with lipid-nanoparticles (LNPs), which are spherical vesicles constituted by ionizable lipids, thanks to a process called PEGylation, which could potentially alter the immunogenic properties of PEG. PEG coats the surface of the LNPs reducing opsonization, aggregation, and improving mRNA delivery to the target cells.

(1) Background: Numerous vaccines are under preclinical and clinical development for prevention of severe course and lethal outcome of coronavirus disease 2019 (COVID-19). In light of high efficacy rates and satisfactory safety profiles, some agents have already reached approval and are now distributed worldwide, with varying availability. Real-world data on cutaneous adverse drug reactions (ADRs) remain limited. (2) Methods: We performed a literature research concerning cutaneous ADRs to different COVID-19 vaccines, and incorporated our own experiences. (3) Results: Injection site reactions are the most frequent side effects arising from all vaccine types. Moreover, delayed cutaneous ADRs may occur after several days, either as a primary manifestation or as a flare of a pre-existing inflammatory dermatosis. Cutaneous ADRs may be divided according to their cytokine profile, based on the preponderance of specific T-cell subsets (i.e., Th1, Th2, Th17/22, Tregs). Specific cutaneous ADRs mimic immunogenic reactions to the natural infection with SARS-CoV-2, which is associated with an abundance of type I interferons. (4) Conclusions: Further studies are required in order to determine the best suitable vaccine type for individual groups of patients, including patients suffering from chronic inflammatory dermatoses.

Fascinating immunologic mechanisms that are crucial for pregnancy can, however, lead to the development of different skin conditions, of which atopic dermatitis (AD) is the most frequent one. AD in pregnancy may occur de novo or as a recurrence or exacerbation of known chronic AD. The changes in hormone levels that occur during pregnancy influence the cytokine balance and can lead to manifestation of eczematous lesions, currently classified as atopic eruption of pregnancy. The diagnosis of atopic eruption of pregnancy may be challenging, especially in patients who developed this skin disease de novo during gestation. The treatment is another challenge, because it needs to be safe for both the mother and especially the unborn child. Emollients make up the basis of the therapy. Topical corticosteroids and calcineurin inhibitors are also safe treatment options, and ultraviolet therapy can be added, if required. Use of cyclosporin A is possible for systemic therapy during pregnancy, whereas safety data on new drugs such as biologics approved for AD are limited to small case series. This review is aimed at summarizing available data on the mechanisms that lead to AD during gestation, differential diagnostic evaluations, and treatment options.

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.

Purpose of the review To provide a cutting-edge overview of recent developments in topical and systemic therapeutic approaches for the treatment of atopic dermatitis (AD). Recent findings Growing knowledge about key pathways in AD and stratification of patient's subgroups have set the basis for a new era of targeted topical and systemic therapy in AD.Different aspects have to be considered in the decision process for topical versus systemic therapy. Further on, co-factors from the patient's side as well as the side of the substances determine the choice of a particular drug/drug type.Tailored medicine in AD treatment comprises drugs of the group of small molecules such as topical Janus kinases-signal transducer and activator of transcription (JAK-STAT) inhibitors or phosphodiesterase 4 inhibitors, and JAK-STAT inhibitors for oral use, as well as monoclonal antibodies for subcutaneous use, which target key cytokines or cytokine receptors in AD pathogenesis. Summary The current stepwise treatment approaches, which are settled on basic therapy and structured patient education and gradually expanded depending on the severity of the disease by stronger topical or even systemic measures, will have to be adapted to the rapid development in the therapeutic field, mirrored by an impressive high number of ongoing clinical studies as well as novel drugs at late stages of clinical trials with so far quite promising results.

International audience; The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.

Background Vaccinations against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are intended to induce an immune response to protect against infection/disease. Allergen immunotherapy (AIT) is thought to induce a (different) immune response, e.g., to induce tolerance to allergens. In this position paper we clarify how to use AIT in temporal relation to COVID-19 vaccination. Four SARS-CoV-2 vaccines are currently approved in the EU, and their possible immunological interactions with AIT are described together with practical recommendations for use. Materials and methods Based on the internationally published literature, this position paper provides specific recommendations for the use of AIT in temporal relation to a SARS-CoV-2 vaccination. Results AIT is used in 1) allergic rhinitis, 2) allergic bronchial asthma, 3) insect venom allergy, 4) food allergy (peanut). Conclusion For the continuation of an ongoing AIT, we recommend an interval of 1 week before and after vaccination for subcutaneous immunotherapy (SCIT). For sublingual immunotherapy (SLIT) and oral immunotherapy (OIT), we recommend taking them up to the day before vaccination and a break of 2 - 7 days after vaccination. Initiation of a new SCIT, SLIT, or OIT should be delayed until 1 week after the day of the second vaccination. For SCIT, we generally recommend an interval of ~ 1 week to COVID-19 vaccination.

Wenige Erkrankungen wurden in den letzten Jahren so intensiv und vielfältig auf verschiedenen Ebenen erforscht wie die atopische Dermatitis (AD). Das liegt zum einen daran, dass es sich um die häufigste chronisch-entzündliche Hauterkrankung handelt, die bis zu 30 % der Kinder und 1-10 % der Erwachsenen betrifft. Zum anderen konnten zahlreiche komplexe Veränderungen auf genetischer Ebene sowie auf Ebene des angeborenen und erworbenen Immunsystems identifiziert werden, die für die Charakterisierung der Patienten und Entwicklung neuer diagnostischer und therapeutischer Ansätze wichtig sind. Trotz der komplexen Pathogenese und immunologischen Unterschiede in verschiedenen Krankheitsstadien, sowie der Heterogenität der Krankheitstrigger, war die Therapie der AD, vor allem der mittelschweren bis schweren Form, lange auf rein symptomatische bzw. unspezifische immunsuppressive Ansätze limitiert [1]. Mit Zulassung des ersten Biologikums zur Behandlung der mittelschweren und schweren AD bei Erwachsenen und dessen Verfügbarkeit auf dem deutschen Markt seit Ende 2017, ist nun Bewegung in das Feld gekommen. In dieser Arbeit werden die aktuellen pathophysiologischen Erkenntnisse zur AD zusammengefasst. Durch die Fortschritte bei der Erforschung der Erkrankung wird eine verbesserte Charakterisierung von Patientensubgruppen und verschiedenen Krankheitsausprägungen möglich, was die Grundlage zukünftig zunehmend individuellerer Behandlungsmöglichkeiten darstellen wird.

Background: N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from more than 20% of allergic patients but have low or no allergenic activity. Objectives: To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE. Methods: One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology. HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-FiveTM insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif. Recombinant HHM proteins were analyzed regarding fold and aggregation by circular dichroism and gel filtration, respectively. IgE reactivity was assessed by ELISA, immunoblotting and quantitative ImmunoCAP measurements. IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes. Results: HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins. The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates. IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4>nCyn d 1>nPla a 2>nJug r 2>nCup a 1>nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2. Conclusion: Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity. Funding Statement: This study was supported by the grants P26728, F4605, F4604 and DK W1248 from the Austrian Science Fund (FWF). Rudolf Valenta is recipient of a Megagrant of the Government of the Russian Federation, grant number 14.W03.31.0024. Declaration of Interests: Rudolf Valenta has received research grants from Biomay AG, Vienna, Austria and Viravaxx, Vienna, Austria. He serves as a consultant for Biomay AG and Viravaxx. Dr. Lupinek reports personal fees from Thermo Fisher Scientific, outside the submitted work. All other authors have nothing to disclose. Ethics Approval Statement: The anonymized analysis of the sera was approved by the ethical committee of the Medical University of Vienna (EK1641/2014).

M.P was supported by a Fellowship from the German Research Foundation (DFG). This work received infrastructure support through the DFG Cluster of Excellence “Inflammation at Interfaces” (grants EXC306 and EXC306/2), and was supported by grants (WE2678/6-1, WE2678/6-2, WE2678/9) from the DFG and the e:Med sysINFLAME grant no. 01ZX1306A from the German Federal Ministry of Education and Research (BMBF). J.E.A.C. and X.F.C.C.W. are funded by A*STAR SPF funding for translational skin research and genetic orphan diseases

COVID-19 vaccines and the role of other potential allergenic components different from PEG. A reply to: “Other excipients than PEG might cause serious hypersensitivity reactions in COVID-19 vaccines”

Peanuts are Leguminosae, commonly known as the legume or pea family, and peanut allergy is among the most common food allergies and the most common cause of fatal food reactions and anaphylaxis.The prevalence of peanut allergy increased 3.5-fold over the past two decades reaching 1.4–2% in Europe and the United States. The reasons for this increase in prevalence are likely multifaceted. Sensitization via the skin appears to be associated with the development of peanut allergy and atopic eczema in infancy is associated with a high risk of developing peanut allergy.Until recently, the only possible management strategy for peanut allergy was strict allergen avoidance and emergency treatment including adrenaline auto-injector in cases of accidental exposure and reaction.This paper discusses the various factors that impact the risks of peanut allergy and the burden of self-management on peanut-allergic children and their caregivers.

Summary Background For the preventive treatment of the 2019 coronavirus disease (COVID-19) an unprecedented global research effort studied the safety and efficacy of new vaccine platforms that have not been previously used in humans. Less than one year after the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral sequence, these vaccines were approved for use in the European Union (EU) as well as in numerous other countries and mass vaccination efforts began. The so far in the EU approved mRNA vaccines BNT162b2 and mRNA-1273 are based on similar lipid-based nanoparticle carrier technologies; however, the lipid components differ. Severe allergic reactions and anaphylaxis after COVID-19 vaccination are very rare adverse events but have drawn attention due to potentially lethal outcomes and have triggered a high degree of uncertainty. Methods Current knowledge on anaphylactic reactions to vaccines and specifically the new mRNA COVID-19 vaccines was compiled using a literature search in Medline, PubMed, as well as the national and international study and guideline registries, the Cochrane Library, and the Internet, with special reference to official websites of the World Health Organization (WHO), US Centers for Disease Control and Prevention (CDC), Robert Koch Institute (RKI), and Paul Ehrlich Institute (PEI). Results Based on the international literature and previous experience, recommendations for prophylaxis, diagnosis and therapy of these allergic reactions are given by a panel of experts. Conclusion Allergy testing is not necessary for the vast majority of allergic patients prior to COVID-19 vaccination with currently licensed vaccines. In case of allergic/anaphylactic reactions after vaccination, allergy workup is recommended, as it is for a small potential risk population prior to the first vaccination. Evaluation and approval of diagnostic tests should be done for this purpose.

Hintergrund: Nachdem sich weltweit die durch den "severe acute respiratory syndrome coronavirus type 2" (SARS-CoV-2) ausgelöste Pandemie eingestellt hatte, kam es und kommt es zu Verunsicherungen von Patienten mit allergischen und atopischen Erkrankungen. Derzeit sind in Deutschland vier Vakzine zur Impfung gegen SARS-CoV-2 durch das Paul-Ehrlich-Institut zugelassen worden und die Impfkampagnen sind bundesweit gestartet worden. Insofern ist es jetzt von hoher Bedeutung, Empfehlungen zu möglichen immunologischen Interaktionen und potenziellen Risiken von immunmodulierenden Substanzen (monoklonale Antikörper, Biologika) unter gleichzeitiger Vakzinierung mit den zugelassenen Impfkandidaten zu geben. Methodik: Dieses Positionspapier gibt konkrete Handlungsempfehlungen auf der Grundlage der aktuellen Literatur zum Einsatz dieser immunmodulierenden Medikamente im zeitlichen Zusammenhang mit einer SARS-CoV-2-Vakzination. Ergebnisse: Die vorliegenden Handlungsempfehlungen beziehen sich auf folgende Erkrankungen, bei denen Biologika zur Anwendung kommen: i) chronisch-entzündliche Hauterkrankungen (atopische Dermatitis, chronische spontane Urtikaria), ii) Asthma bronchiale und iii) chronische Rhinosinusitis mit Nasenpolypen (CRSwNP). Patienten mit atopischer Dermatitis oder chronischer spontaner Urtikaria haben kein erhöhtes Risiko für allergische Reaktionen bei der COVID-19-Vakzinierung. Dennoch kann es durch eine Impfung zu einer vorübergehenden Ekzemverschlechterung aufgrund der allgemeinen Immunstimulation kommen. Patienten, bei denen eine Systemtherapie mit einem Biologikum durchgeführt wird, können geimpft werden. Bei Patienten mit schwerem Asthma und gleichzeitiger Biologikagabe findet sich ebenfalls kein erhöhtes Risiko für eine allergische Reaktion nach einer COVID-19-Impfung und diese wird empfohlen. Auch bei Patienten mit CRSwNP ist kein erhöhtes Risiko für allergische Impfreaktionen bekannt und die Fortführung oder Neueinleitung einer Biologikatherapie werden auch bei einer geplanten COVID-19-Impfung empfohlen. Generell sollte die COVID-19-Vakzinierung zwischen zwei Injektionen der entsprechenden Biologika erfolgen, das heißt im Abstand von mindestens einer Woche nach der vorherigen beziehungsweise vor der nächsten Biologikagabe. Schlussfolgerung: Die Therapie mit Biologika zur Behandlung von atopischer Dermatitis, chronischer spontaner Urtikaria, Bronchialasthma und CRSwNP sollte während der jetzt durchgeführten COVID-19-Impfkampagnen unverändert fortgeführt werden, wobei eventuell die Therapieintervalle der Biologikatherapie geringfügig angepasst werden müssen (Empfehlung DGAKI/AeDA, 22. März 2021).

Background: Vaccinations against Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are intended to induce an immune response in the sense of protection against infection/disease. Allergen-specific immunotherapy (AIT) is also thought to induce a (different) immune response in the sense of tolerance to allergens. There is uncertainty among patients and physicians regarding the use of vaccination and AIT in temporal relation, which this position paper aims to clarify. The four vaccines currently approved in Germany for vaccination against SARS-CoV-2 are described and possible immunological interactions with AIT are highlighted, as well as practical recommendations for action. Methods: Based on the current internationally published literature, this position paper provides specific recommendations for action regarding the use of AIT in temporal relation to a SARS-CoV-2 vaccination. Results: The present recommendations for action relate to the following conditions for which AIT is used i) allergic rhinitis, ii) allergic bronchial asthma, iii) insect venom allergy, iiii) food allergy (peanut). Conclusions: If vaccination is imminent, initiation of subcutaneous (SCIT), sublingual (SLIT), or oral (OIT) AIT should be delayed until 1 week after the 2nd vaccination date. Thus, there should generally be an interval of approximately 1 week between SCIT and -COVID-19 vaccination. For the continuation of an ongoing AIT, we recommend an interval of 1 week before and after vaccination for SCIT. For SLIT and OIT, we recommend taking them up to the day before vaccination and taking a break from SLIT and OIT for 2 - 7 days after vaccination.