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Abstract: Background: N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >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.
Keywords: allergy and immunology, allergens, glycoproteins, molecular diagnostic technique, recombinant glycoproteins, molecular allergology, component-resolved diagnosis
Published in DiRROS: 16.10.2020; Views: 1492; Downloads: 1079
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Abstract: This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. There is no reason to avoid propofol in egg, soy, or peanut allergy. The allergenic determinants have been characterised for fish, shellfish, and povidone iodine, but remain unknown for iodinated contrast agents. Iodinated drugs may be used in seafood allergy. Evidence supporting the risk for protamine allergy in fish allergy and in neutral protamine Hagedorn insulin use is lacking. Conversely, cross-reactivity to gelatin-based colloid may occur in agal syndrome. Atopy and allergic asthma along with other non-allergic conditions, such as NSAID-exacerbated respiratory disease, chronic urticaria, mastocytosis, and hereditary or acquired angioedema, are not risk factors for IgEmediated drug allergy, but there is a perioperative risk associated with the potential for exacerbation of the various conditions.
Keywords: allergy and immunology, drug hypersensitivity, food hypersensitivity, immediate hypersensitivity, anaphylaxis, anesthesia, drug-related side effects and adverse reactions, perioperative period, adverse effects
Published in DiRROS: 16.10.2020; Views: 1377; Downloads: 467
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Abstract: Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.
Keywords: allergy and immunology, drug hypersensitivity, anesthesia, drug-related side effects and adverse reactions, anaphylaxis, epinephrine, Delphi technique, perioperative period, allergic reactions, hypersensitivity reaction, adrenaline, perioperative anaphylaxis, allergy testing, guideline
Published in DiRROS: 09.10.2020; Views: 1370; Downloads: 420
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Abstract: Asthma is a severe and chronic disabling disease affecting more than 300 million people world-wide. While in the past few drugs for treatment of asthma were available, new treatment options are currently emerging which appear to be highly effective in certain subgroups of patients. Accordingly there is a need for biomarkers which allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on micro-arrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed which may discriminate two of the most common forms of asthma, i.e., allergen- and virus-triggered asthma. In this perspective we argue that classification of asthma patients according to these common trigger factors may open new possibilities for personalized management of asthma.
Keywords: allergy and immunology, asthma, signs and symptoms, respiratory, rhinovirus, allergens, microarray analysis, precision medicine, wheeze
Published in DiRROS: 31.07.2020; Views: 2268; Downloads: 1092
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