IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4.

BACKGROUND: Alpha-gal (Galα1-3Galß1-4GlcNAc) is a carbohydrate with the potential to elicit fatal allergic reactions to mammalian meat and drugs of mammalian origin. This type of allergy is induced by tick bites, and therapeutic options for this skin-driven food allergy are limited to the avoidance of the allergen and treatment of symptoms. Thus, a better understanding of the immune mechanisms resulting in sensitization through the skin is crucial, especially in the case of a carbohydrate allergen for which underlying immune responses are poorly understood. OBJECTIVE: We aimed to establish a mouse model of alpha-gal allergy for in-depth immunologic analyses. METHODS: Alpha-galactosyltransferase 1-deficient mice devoid of alpha-gal glycosylations were sensitized with the alpha-gal-carrying self-protein mouse serum albumin by repetitive intracutaneous injections in combination with the adjuvant aluminum hydroxide. The role of basophils and IL-4 in sensitization was investigated by antibody-mediated depletion. RESULTS: Alpha-gal-sensitized mice displayed increased levels of alpha-gal-specific IgE and IgG1 and developed systemic anaphylaxis on challenge with both alpha-gal-containing glycoproteins and glycolipids. In accordance with alpha-gal-allergic patients, we detected elevated numbers of basophils at the site of sensitization as well as increased numbers of alpha-gal-specific B cells, germinal center B cells, and B cells of IgE and IgG1 isotypes in skin-draining lymph nodes. By depleting IL-4 during sensitization, we demonstrated for the first time that sensitization and elicitation of allergy to alpha-gal and correspondingly to a carbohydrate allergen is dependent on IL-4. CONCLUSION: These findings establish IL-4 as a potential target to interfere with alpha-gal allergy elicited by tick bites.

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Allergy and Environmental Medicine (GPA), German Respiratory Society (DGP), and the Austrian Society for Allergy and Immunology (ÖGAI).

Hymenoptera venom (HV) is injected into the skin during a sting by Hymenoptera such as bees or wasps. Some components of HV are potential allergens and can cause large local and/or systemic allergic reactions (SAR) in sensitized individuals. During their lifetime, ~ 3% of the general population will develop SAR following a Hymenoptera sting. This guideline presents the diagnostic and therapeutic approach to SAR following Hymenoptera stings. Symptomatic therapy is usually required after a severe local reaction, but specific diagnosis or allergen immunotherapy (AIT) with HV (VIT) is not necessary. When taking a patient's medical history after SAR, clinicians should discuss possible risk factors for more frequent stings and more severe anaphylactic reactions. The most important risk factors for more severe SAR are mast cell disease and, especially in children, uncontrolled asthma. Therefore, if the SAR extends beyond the skin (according to the Ring and Messmer classification: grade > I), the baseline serum tryptase concentration shall be measured and the skin shall be examined for possible mastocytosis. The medical history should also include questions specific to asthma symptoms. To demonstrate sensitization to HV, allergists shall determine concentrations of specific IgE antibodies (sIgE) to bee and/or vespid venoms, their constituents and other venoms as appropriate. If the results are negative less than 2 weeks after the sting, the tests shall be repeated (at least 4 - 6 weeks after the sting). If only sIgE to the total venom extracts have been determined, if there is double sensitization, or if the results are implausible, allergists shall determine sIgE to the different venom components. Skin testing may be omitted if in-vitro methods have provided a definitive diagnosis. If neither laboratory diagnosis nor skin testing has led to conclusive results, additional cellular testing can be performed. Therapy for HV allergy includes prophylaxis of reexposure, patient self treatment measures (including use of rescue medication) in the event of re-stings, and VIT. Following a grade I SAR and in the absence of other risk factors for repeated sting exposure or more severe anaphylaxis, it is not necessary to prescribe an adrenaline auto-injector (AAI) or to administer VIT. Under certain conditions, VIT can be administered even in the presence of previous grade I anaphylaxis, e.g., if there are additional risk factors or if quality of life would be reduced without VIT. Physicians should be aware of the contraindications to VIT, although they can be overridden in justified individual cases after weighing benefits and risks. The use of ß-blockers and ACE inhibitors is not a contraindication to VIT. Patients should be informed about possible interactions. For VIT, the venom extract shall be used that, according to the patient's history and the results of the allergy diagnostics, was the trigger of the disease. If, in the case of double sensitization and an unclear history regarding the trigger, it is not possible to determine the culprit venom even with additional diagnostic procedures, VIT shall be performed with both venom extracts. The standard maintenance dose of VIT is 100 µg HV. In adult patients with bee venom allergy and an increased risk of sting exposure or particularly severe anaphylaxis, a maintenance dose of 200 µg can be considered from the start of VIT. Administration of a non-sedating H1-blocking antihistamine can be considered to reduce side effects. The maintenance dose should be given at 4-weekly intervals during the first year and, following the manufacturer's instructions, every 5 - 6 weeks from the second year, depending on the preparation used; if a depot preparation is used, the interval can be extended to 8 weeks from the third year onwards. If significant recurrent systemic reactions occur during VIT, clinicians shall identify and as possible eliminate co-factors that promote these reactions. If this is not possible or if there are no such co-factors, if prophylactic administration of an H1-blocking antihistamine is not effective, and if a higher dose of VIT has not led to tolerability of VIT, physicians should should consider additional treatment with an anti IgE antibody such as omalizumab as off lable use. For practical reasons, only a small number of patients are able to undergo sting challenge tests to check the success of the therapy, which requires in-hospital monitoring and emergency standby. To perform such a provocation test, patients must have tolerated VIT at the planned maintenance dose. In the event of treatment failure while on treatment with an ACE inhibitor, physicians should consider discontinuing the ACE inhibitor. In the absence of tolerance induction, physicians shall increase the maintenance dose (200 µg to a maximum of 400 µg in adults, maximum of 200 µg HV in children). If increasing the maintenance dose does not provide adequate protection and there are risk factors for a severe anaphylactic reaction, physicians should consider a co-medication based on an anti-IgE antibody (omalizumab; off-label use) during the insect flight season. In patients without specific risk factors, VIT can be discontinued after 3 - 5 years if maintenance therapy has been tolerated without recurrent anaphylactic events. Prolonged or permanent VIT can be considered in patients with mastocytosis, a history of cardiovascular or respiratory arrest due to Hymenoptera sting (severity grade IV), or other specific constellations associated with an increased individual risk of recurrent and/or severe SAR (e.g., hereditary α-tryptasemia). In cases of strongly increased, unavoidable insect exposure, adults may receive VIT until the end of intense contact. The prescription of an AAI can be omitted in patients with a history of SAR grade I and II when the maintenance dose of VIT has been reached and tolerated, provided that there are no additional risk factors. The same holds true once the VIT has been terminated after the regular treatment period. Patients with a history of SAR grade ≥ III reaction, or grade II reaction combined with additional factors that increase the risk of non response or repeated severe sting reactions, should carry an emergency kit, including an AAI, during VIT and after regular termination of the VIT.

Confocal corrected attenuation coefficient imaging in phantoms and in vivo using chromatic focal shift calibration.

Optical coherence tomography (OCT) is conventionally used for structural imaging of tissue. Calibrating the intensity values of OCT images can give information on the tissue's inherent optical properties, such as the attenuation coefficient, which can provide an additional parameter to quantify possible pathological changes. To obtain calibrated intensity values, the focus position and Rayleigh length of the incident beam need to be known. We explore the feasibility of extracting the focus position from an OCT scan acquired with a single focus setting using the chromatic aberration of the system. The chromatic focal shift of an OCT system is exploited to achieve different focus positions for sub-spectrum reconstructed OCT images. The ratios of these images are used to estimate the focus position. Reconstruction of a high-resolution B-scan from coherent addition of sub-spectrum confocal function corrected B-scans and subsequent high-resolution OCT attenuation coefficient imaging is demonstrated. Furthermore, we introduce a method to experimentally determine the chromatic focal shifts of an OCT system in phantoms and an in vivo human retina. These shifts are compared to the theoretically expected shifts calculated with ray tracing.

Ti-Doping in Silica-Supported PtZn Propane Dehydrogenation Catalysts: From Improved Stability to the Nature of the Pt-Ti Interaction.

Propane dehydrogenation is an important industrial reaction to access propene, the world's second most used polymer precursor. Catalysts for this transformation are required to be long living at high temperature and robust toward harsh oxidative regeneration conditions. In this work, combining surface organometallic chemistry and thermolytic molecular precursor approach, we prepared well-defined silica-supported Pt and alloyed PtZn materials to investigate the effect of Ti-doping on catalytic performances. Chemisorption experiments and density functional calculations reveal a significant change in the electronic structure of the nanoparticles (NPs) due to the Ti-doping. Evaluation of the resulting materials PtZn/SiO2 and PtZnTi/SiO2 during long deactivation phases reveal a stabilizing effect of Ti in PtZnTi/SiO2 with a kd of 0.015 h-1 compared to PtZn/SiO2 with a kd of 0.022 h-1 over 108 h on stream. Such a stabilizing effect is also present during a second deactivation phase after applying a regeneration protocol to the materials under O2 and H2 at high temperatures. A combined scanning transmission electron microscopy, in situ X-ray absorption spectroscopy, electron paramagnetic resonance, and density functional theory study reveals that this effect is related to a sintering prevention of the alloyed PtZn NPs in PtZnTi/SiO2 due to a strong interaction of the NPs with Ti sites. However, in contrast to classical strong metal-support interaction, we show that the coverage of the Pt NPs with TiOx species is not needed to explain the changes in adsorption and reactivity properties. Indeed, the interaction of the Pt NPs with TiIII sites is enough to decrease CO adsorption and to induce a red-shift of the CO band because of electron transfer from the TiIII sites to Pt0.

Methane Oxidation over Cu2+ /[CuOH]+ Pairs and Site-Specific Kinetics in Copper Mordenite Revealed by Operando Electron Paramagnetic Resonance and UV/Visible Spectroscopy.

Cu-exchanged mordenite (MOR) is a promising material for partial CH4 oxidation. The structural diversity of Cu species within MOR makes it difficult to identify the active Cu sites and to determine their redox and kinetic properties. In this study, the Cu speciation in Cu-MOR materials with different Cu loadings has been determined using operando electron paramagnetic resonance (EPR) and operando ultraviolet-visible (UV/Vis) spectroscopy as well as in situ photoluminescence (PL) and Fourier-transform infrared (FTIR) spectroscopy. A novel pathway for CH4 oxidation involving paired [CuOH]+ and bare Cu2+ species has been identified. The reduction of bare Cu2+ ions facilitated by adjacent [CuOH]+ demonstrates that the frequently reported assumption of redox-inert Cu2+ centers does not generally apply. The measured site-specific reaction kinetics show that dimeric Cu species exhibit a faster reaction rate and a higher apparent activation energy than monomeric Cu2+ active sites highlighting their difference in the CH4 oxidation potential.

Copper(II) defect-cubane water oxidation electrocatalysts: from molecular tetramers to oxidic nanostructures.

We report on the synthesis and spectroscopic evidence for a sequence of structural transformations of a new defect-cubane type copper complex, [Cu4(pyalk)4(OAc)4](ClO4)(HNEt3), which acts as a pre-catalyst for water oxidation. In situ and post-catalytic studies showed that the tetrameric complex undergoes a structural transformation into dimeric and monomeric species, induced by water molecules and carbonate anions, respectively. Further, the observed electrocatalytic water oxidation activity has been confirmed to arise from in situ-generated Cu(II) oxidic nanostructures at the electrode interface.

Information-Based Plastic Material Tracking for Circular Economy-A Review.

At the moment, it looks like the plastics recycling industry is skimming only low-hanging fruits of its business. To reach intended targets, a greater effort and disruptive innovations are necessary. Physical- or digital-information-based solutions for tracking plastic material can support the circular economy and help to overcome hurdles along the value chain. In this paper, the scientific literature and initiatives in four different technology areas for information-based tracking solutions are reviewed and analyzed. Physical markers can improve sorting efficiencies on short notice but adhere some technical difficulties. Blockchain as a new concept promises high transparency and security, with the drawbacks of energy-intense verification and technical uncertainties. As a third group, the digital product passport claims a combination of physical and digital solutions with open questions on data ownership. The fourth and last group includes standards and certification systems that aim for maximum consensus with slow market implementation. To enable an integrated circular economy of plastics, plastic material tracking solutions must experience broad acceptance by all players along the value chain in the plastics industry and they should additionally be supported by society.

Development and Evaluation of Options for Action to Progress on the SDG 6 Targets in Austria.

The Agenda 2030 of the United Nations stipulates an ambitious set of 17 Sustainable Development Goals (SDGs). They were globally agreed upon and demand coherent, context-specific implementation at the national level. To address the complexity of challenges therein, the Agenda is designed to be integrated, indivisible, and universal. The numerous multifaceted interactions in-between the SDGs and with corresponding measures pose a complex challenge for decision-makers implementing them worldwide that requires support for a comprehensive discourse in the science-society-policy arena. Research on the interactions between the SDGs has been flourishing and can help to understand where policy options might be most successfully located. A catalytic effect on several other goals is, e.g., often attributed to SDG 6 on water and sanitation. However, beyond the where to locate policy options, it is similarly important to understand how potential policy options would affect the SDGs and their targets. We developed eleven options and 85 measures as context-specific pathways to advance the SDG 6 Targets in Austria. As a country in the Global North and with a generally far-established water and sanitation infrastructure and management, this responds to the Agenda's demand for universal applicability and can serve as an example to illustrate potential challenges beyond basic infrastructure provision and management. The proposed options cover resources-oriented sanitation, blue-green-brown infrastructure, efficient use and integrated management of water resources, maintenance and restoration of ecological functions of inland waters, reduction of diffuse discharge of nutrients and problematic substances as well as trace substances, water, sanitation and hygiene in public spaces, groundwater protection, development cooperation as well as co-design and co-creation. Their effects on the SDG 6 Targets are evaluated using a 7-point-scale. The evaluation method is simple and practicable, and fosters discourse on the entire water cycle amongst the expert group applying the method. The evaluated effects on the targets are found to be unanimously positive or neutral, but trade-offs might arise when including other SDGs in the assessment, making an expansion of the evaluation necessary for coherent implementation. The results can be used as a baseline to support follow-up discussions with stakeholders and decision-makers.

A Robust and Efficient Propane Dehydrogenation Catalyst from Unexpectedly Segregated Pt2Mn Nanoparticles.

The increasing demand for short chain olefins like propene for plastics production and the availability of shale gas make the development of highly performing propane dehydrogenation (PDH) catalysts, robust toward industrially applied harsh regeneration conditions, a highly important field of research. A combination of surface organometallic chemistry and thermolytic molecular precursor approach was used to prepare a nanometric, bimetallic Pt-Mn material (3 wt % Pt, 1.3 wt % Mn) supported on silica via consecutive grafting of a Mn and Pt precursor on surface OH groups present on the support surface, followed by a treatment under a H2 flow at high temperature. The material exhibits a 70% fraction of the overall Mn as MnII single sites on the support surface; the remaining Mn is incorporated in segregated Pt2Mn nanoparticles. The material shows great performance in PDH reaction with a low deactivation rate. In particular, it shows outstanding robustness during repeated regeneration cycles, with conversion and selectivity stabilizing at ca. 37 and 98%, respectively. Notably, a material with a lower Pt loading of only 0.05 wt % shows an outstanding catalytic performance─initial productivity of 4523 gC3H6/gPt h and an extremely low kd of 0.003 h-1 under a partial pressure of H2, which are among the highest reported productivities. A combined in situ X-ray absorption spectroscopy, scanning transmission electron microscopy, electron paramagnetic resonance, and metadynamics at the density functional theory level study could show that the strong interaction between the MnII-decorated support and the unexpectedly segregated Pt2Mn particles is most likely responsible for the outstanding performance of the investigated materials.

α-Gal present on both glycolipids and glycoproteins contributes to immune response in meat-allergic patients.

BACKGROUND: The α-Gal syndrome is associated with the presence of IgE directed to the carbohydrate galactose-α-1,3-galactose (α-Gal) and is characterized by a delayed allergic reaction occurring 2 to 6 hours after ingestion of mammalian meat. On the basis of their slow digestion and processing kinetics, α-Gal-carrying glycolipids have been proposed as the main trigger of the delayed reaction. OBJECTIVE: We analyzed and compared the in vitro allergenicity of α-Gal-carrying glycoproteins and glycolipids from natural food sources. METHODS: Proteins and lipids were extracted from pork kidney (PK), beef, and chicken. Glycolipids were purified from rabbit erythrocytes. The presence of α-Gal and IgE binding of α-Gal-allergic patient sera (n = 39) was assessed by thin-layer chromatography as well as by direct and inhibition enzyme-linked immunosorbent assay. The in vitro allergenicity of glycoproteins and glycolipids from different meat extracts was determined by basophil activation test. Glycoprotein stability was evaluated by simulated gastric and intestinal digestion assays. RESULTS: α-Gal was detected on glycolipids of PK and beef. Patient IgE antibodies recognized α-Gal bound to glycoproteins and glycolipids, although binding to glycoproteins was more potent. Rabbit glycolipids were able to strongly activate patient basophils, whereas lipid extracts from PK and beef were also found to trigger basophil activation, but at a lower capacity compared to the respective protein extracts. Simulated gastric digestion assays of PK showed a high stability of α-Gal-carrying proteins in PK. CONCLUSION: Both α-Gal-carrying glycoproteins and glycolipids are able to strongly activate patient basophils. In PK and beef, α-Gal epitopes seem to be less abundant on glycolipids than on glycoproteins, suggesting a major role of glycoproteins in delayed anaphylaxis upon consumption of these food sources.

Do basophil activation tests help elucidate allergic reactions to the ingredients in COVID-19 vaccines?

The worldwide use of COVID-19 vaccines has shown that immediate allergic reactions to the ingredients are rare but should be clarified by means of an allergological work-up. This review aims to highlight the current state of knowledge and possible pathogenesis based on the literature published to date. In addition to recording a detailed history and performing skin tests, cellular tests (basophil activation or basophil histamine release test) by using the vaccines or modified compounds containing polyethylene glycol (PEG), rather than unmodified PEGs, have proven to be particularly helpful. Negative results with vaccines seem to indicate tolerance. Details of the performance of these cellular tests with different vaccines, PEGs of different molecular weights, other ingredients of the vaccines, as well as other PEGylated drugs, and the results in the context of COVID-19 vaccination of various working groups worldwide are summarized.

Experience with polyethylene glycol allergy-guided risk management for COVID-19 vaccine anaphylaxis.

BACKGROUND: Polyethylene glycol (PEG) may elicit anaphylaxis to COVID-19 mRNA vaccines, and guidance for patients at risk is needed. METHODS: In retrospective patients with PEG allergy collected from 2006 till 2019, clinical, skin, and basophil activation test (BAT) characteristics discriminative for PEG allergy were analyzed and compared with the literature. In 421 prospective real-life patients asking for allergy workup for COVID-19 vaccine hypersensitivity in 2020/2021, risk assessment was performed and tolerance of the recommended vaccination approach was assessed. RESULTS: Ten patients with PEG allergy were found in the retrospective cohort. Patients reacted with immediate anaphylaxis (100%) not only to PEG-based laxatives/bowel preparations or injections, but also to cold medication, antiseptics, analgetics, or antibiotics. Skin tests ± BAT with PEG ± elicitors were positive in 10/10. Provocation tests were positive in 7/9 patients. From the prospective cohort, 370/421 patients self-reporting increased risk for vaccine allergy lacked criteria necessitating allergy workup and were recommended for routine vaccination. A total of 51/421 patients were tested, and three (6%) with PEG allergy were identified, whereas 48 patients remained negative in skin tests. Vaccination was recommended in all those patients. No hypersensitivity reactions were reported to vaccination including six PEG-allergic patients tolerating COVID-19 vaccination. CONCLUSIONS: Taking a detailed history excluded PEG allergy in most referred patients and enabled direct safe vaccination. Immediate urticaria/anaphylaxis to typical elicitors identified patients requiring PEG allergy workup. Skin tests ± BAT identified PEG allergy and helped to select the vaccine and the vaccination approach. Even PEG-allergic patients can tolerate COVID-19 vaccines.

Investigation of methods to extract confocal function parameters for the depth resolved determination of attenuation coefficients using OCT in intralipid samples, titanium oxide phantoms, and in vivo human retinas.

The attenuation coefficient provides a quantitative parameter for tissue characterization and can be calculated from optical coherence tomography (OCT) data, but accurate determination requires compensation for the confocal function. We present extensive measurement series for extraction of the focal plane and the apparent Rayleigh length from the ratios of OCT images acquired with different focus depths and compare these results with two alternative approaches. By acquiring OCT images for a range of different focus depths the optimal focus plane difference is determined for intralipid and titanium oxide (TiO2) phantoms with different scatterer concentrations, which allows for calculation of the attenuation coefficient corrected for the confocal function. The attenuation coefficient is determined for homogeneous intralipid and TiO2 samples over a wide range of concentrations. We further demonstrate very good reproducibility of the determined attenuation coefficient of layers with identical scatter concentrations in a multi-layered phantom. Finally, this method is applied to in vivo retinal data.

Differentiation of Polyamide 6, 6.6, and 12 Contaminations in Polyolefin-Recyclates Using HPLC Coupled to Drift-Tube Ion-Mobility Quadrupole Time-of-Flight Mass Spectrometry.

Recycling is a current hot topic with a focus especially on plastics. The quality of such plastic recyclates is of utmost importance for further processing because impurities lead to a reduction thereof. Contaminations originating from other polymers are highly problematic due to their immiscibility with the recyclate, leading to possible product failures. Therefore, methods for the determination of polymer impurities in recyclates should be investigated. In this paper, an approach for the identification of three different polyamide grades (polyamide 6, 6.6, and 12) is presented, applicable for the analysis of polyolefin-recyclates. An HPLC equipped with a drift-tube ion-mobility QTOF-MS was used for the identification and differentiation of compounds originating from the polyamides, which were then used as markers. These marker compounds are specific for each type and can be identified by their corresponding value of the collision cross section (CCS). After a simple sample preparation, all three types of polyamides were identified within one measurement. In particular, the problematic differentiation of polyamide 6 and 6.6 was easily made possible.

Development of an LC-MS method for the semiquantitative determination of polyamide 6 contaminations in polyolefin recyclates.

Recycling will be of increasing importance in the future, especially for plastic packaging waste mainly consisting of polyolefins. One major problem of recyclates comprises impurities which can have a significant negative impact on future product properties. Polyamide 6 can be found widely as contaminant in recycled polyolefins, leading to a need of quantification methods thereof. In this paper, a method development for the quantitative analysis of polyamide 6 is presented based on analysing ε-caprolactam and related cyclic oligomers as marker compounds in model recyclates of high- and low-density polyethylene and polypropylene compounded with low amounts of polyamide 6. For the method development and tentative identification of the different cyclic compounds, a HPLC-QTOF-MS was used and it was possible to detect six different compounds, ε-caprolactam and the corresponding cyclic di- to hexamer. The quantification was performed with a HPLC-QQQ-MS, equipped with a HILIC column, after sample preparation via microwave-assisted extraction. It could be shown that a good linearity from 0.2 up to 5 wt% polyamide 6 in the different polyolefins can be achieved. The cyclic trimer and tetramer show a low limit of quantification and are therefore well-suited for the quantification, whereas the other cyclic compounds can be then used as qualifiers to avoid false positives. To guarantee the applicability of the method, six real recyclate materials were analysed, whereby in three of them low amounts of polyamide 6 could be detected. Graphical abstract.

The History of Carbohydrates in Type I Allergy.

Although first described decades ago, the relevance of carbohydrate specific antibodies as mediators of type I allergy had not been recognized until recently. Previously, allergen specific IgE antibodies binding to carbohydrate epitopes were considered to demonstrate a clinically irrelevant cross-reactivity. However, this changed following the discovery of type I allergies specifically mediated by oligosaccharide structures. Especially the emerging understanding of red meat allergy characterized by IgE directed to the oligosaccharide alpha-gal showed that carbohydrate-mediated reactions can result in life threatening systemic anaphylaxis which in contrast to former assumptions proves a high clinical relevance of some carbohydrate allergens. Within the scope of this review article, we illustrate the historical development of carbohydrate-allergen-research, reaching from only diagnostically relevant crossreactive-carbohydrate-determinants to clinically important antigens mediating type I allergy. Focusing on clinical and immunological features of the alpha-gal syndrome, we highlight the discovery of oligosaccharides as potentially highly immunogenic antigens and mediators of type I allergy, report what is known about the route of sensitization and the immunological mechanisms involved in sensitization and elicitation phase of allergic responses as well as currently available diagnostic and therapeutic tools. Finally, we briefly report on carbohydrates being involved in type I allergies different from alpha-gal.

Site-directed attachment of photoexcitable spin labels for light-induced pulsed dipolar spectroscopy.

Photoexcited triplet states are gaining popularity as spin labels in pulsed electron paramagnetic resonance (EPR) spectroscopy. Here, we demonstrate that the fluorophores Eosin Y, Rose Bengal and Atto Thio12 are suitable markers for distance determination by laser-induced magnetic dipole (LaserIMD) spectroscopy in proteins that lack an intrinsic photoexcitable center.

Spatial distribution of alpha-gal in Ixodes ricinus - A histological study.

Alpha-gal syndrome is a complex allergic disease in humans that is caused by specific IgE (sIgE) against the carbohydrate galactose-α-1,3-galactose (alpha-gal). Tick saliva contains alpha-gal, and tick bites are considered a major cause of the induction of alpha-gal-sIgE. The origin of alpha-gal in tick saliva remains unclarified. The presence of alpha-gal in tick tissue was visualized in this study to provide an overview of the spatial distribution of alpha-gal and to further elucidate the origin of alpha-gal in tick saliva. Fed and unfed Ixodes ricinus females were examined by histology, immunohistochemistry, immunofluorescence, transmission electron microscopy and immunoelectron microscopy using the alpha-gal-specific monoclonal antibody M86 and Marasmius oreades agglutinin (MOA) lectin. Alpha-gal epitopes were detected in the midgut, hemolymph and salivary glands, and the immunofluorescence analysis revealed signs of the endocytosis of alpha-gal-containing constituents during the process of hematophagy. Alpha-gal epitopes in endosomes of the digestive gut cells of the ticks were observed via immunoelectron microscopy. Alpha-gal epitopes were detected in dried droplets of hemolymph from unfed ticks. Intense staining of alpha-gal epitopes was found in type II granular acini of the salivary glands of fed and unfed ticks. Our data suggest that alpha-gal is not ubiquitously expressed in tick tissue but is present in both fed and unfed ticks. The findings also indicate that both the metabolic incorporation of constituents from a mammalian blood meal and endogenous production contribute to the presence of alpha-gal epitopes in ticks.

Human sleep consolidates allergic responses conditioned to the environmental context of an allergen exposure.

Allergies are highly prevalent, and allergic responses can be triggered even in the absence of allergens due to Pavlovian conditioning to a specific cue. Here we show in humans suffering from allergic rhinitis that merely reencountering the environmental context in which an allergen was administered a week earlier is sufficient to trigger an allergic response-but only if participants had slept after allergen exposure. This context-conditioning effect was entirely absent when participants stayed awake the night after allergen exposure or were tested in a different context. Unlike in context conditioning, cue conditioning (to an odor stimulus) occurred independently of sleep, a differential pattern that is likewise observed for conditioning in the behavioral domain. Our findings provide evidence that allergic responses can be conditioned to contextual information alone, even after only a single-trial conditioning procedure, and that sleep is necessary to consolidate this rapidly acquired maladaptive response. The results unravel a mechanism that could explain part of the strong psychological impact on allergic responses.