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1.
Impact of Different Lipid Ligands on the Stability and IgE-Binding Capacity of the Lentil Allergen Len c 3.
Finkina, EI, Melnikova, DN, Bogdanov, IV, Matveevskaya, NS, Ignatova, AA, Toropygin, IY, Ovchinnikova, TV
Biomolecules. 2020;(12)
Abstract
Previously, we isolated the lentil allergen Len c 3, belonging to the class of lipid transfer proteins, cross-reacting with the major peach allergen Pru p 3 and binding lipid ligands. In this work, the allergenic capacity of Len c 3 and effects of different lipid ligands on the protein stability and IgE-binding capacity were investigated. Impacts of pH and heat treating on ligand binding with Len c 3 were also studied. It was shown that the recombinant Len c 3 (rLen c 3) IgE-binding capacity is sensitive to heating and simulating of gastroduodenal digestion. While being heated or digested, the protein showed a considerably lower capacity to bind specific IgE in sera of allergic patients. The presence of lipid ligands increased the thermostability and resistance of rLen c 3 to digestion, but the level of these effects was dependent upon the ligand's nature. The anionic lysolipid LPPG showed the most pronounced protective effect which correlated well with experimental data on ligand binding. Thus, the Len c 3 stability and allergenic capacity can be retained in the conditions of food heat cooking and gastroduodenal digestion due to the presence of certain lipid ligands.
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2.
Atopic dermatitis in Taiwanese children: The laboratory values that correlate best to the SCORAD index are total IgE and positive Cheddar cheese IgE.
Kuo, HC, Chu, CH, Su, YJ, Lee, CH
Medicine. 2020;(30):e21255
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Abstract
Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease associated with a personal or family history of atopic diseases. Determining the objective severity scoring of AD index (SCORAD) and total immunoglobulin E (IgE) to help to stage the severity (lesions extent and intensity of the lesions and then the itch and sleep disturbance they may cause) of AD in children.In this study, we adopted the SCORAD index, which consists of severity, area, and sleep disturbance, to evaluate the AD status of children up to 18 years old. We examined the blood levels of total serum IgE, white blood cell count/differential count (WBC/DC), eosinophil counts (EC), eosinophil cationic protein (ECP) and specific IgE.A total of 208 children with AD were enrolled in this study. Serum IgE values and a number of specific IgE that are positive significantly different SCORAD index through simple linear regression; however, after multiple linear regression, only IgE values (95% CI: 0.001-0.004, P < .001), total WBC count (95% CI: 0.112-1.736, P = .026), EC (95% CI: 0.045-6.706, P = .047), and specific IgE to Cheddar cheese (95% CI: 1.814-16.731, P = .015) remain different. After applying the Phi coefficient, we found that specific IgE to tuna (r = 0.632), codfish (r = 0.613), and clam (r = 0.613) each had a moderate correlation with specific IgE to Cheddar cheese. The 6 most common allergens were found to be mite (D. Farinae: 65.9%), mite (D. Pterony: 64.9%), house dust (47.6%), cockroach mix (37.0%), shrimp (30.8%), and crab (22.6%). Covariates of SCORAD index, severity, area, and sleep disturbance differed.In this study, we found that total IgE values, specific IgE values, WBC, EC, and specific IgE to Cheddar cheese have significant correlations with SCORAD index in AD of Taiwanese children.
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Immunoglobulin E (IgE)-Mediated Food Allergy in Children: Epidemiology, Pathogenesis, Diagnosis, Prevention, and Management.
Barni, S, Liccioli, G, Sarti, L, Giovannini, M, Novembre, E, Mori, F
Medicina (Kaunas, Lithuania). 2020;(3)
Abstract
A food allergy is an immunoglobulin E (IgE)-mediated hypersensitive reaction to food, which consists in the appearance of allergic symptoms; it can vary from common urticaria to even fatal anaphylaxis. The prevalence of food allergies has been increasing in the past twenty years and it represents a major public health problem in industrialized countries. The mechanism that leads to food allergies is the lack of immunologic and clinical tolerance to food allergens. The diagnosis of IgE-mediated food allergies is based on the combined use of a detailed medical history, in-vivo, and in-vitro research of specific IgE, the elimination diet, and the double-blind placebo-controlled food challenge. The only currently available treatment for allergies is the strict elimination diet. This type of attitude, which we could define as "passive", does not overcome the risk of accidental reactions due to involuntary intake of the culprit food. For food allergy management, an "active" approach is urgently needed, such as specific allergen immunotherapy, which is currently under development and only used for research purposes. This article aims to give an updated review of IgE-mediated food allergies in pediatric populations in terms of epidemiology, pathogenesis, prevention, diagnosis, and management.
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Serum immunoglobulin E reactivity to cross-reacting panallergen components in north-eastern Poland patients pollen sensitized.
Kowal, K, Pampuch, A, Sacharzewska, E, Swiebocka, E, Siergiejko, Z, Siergiejko, G, Chruszcz, M, DuBuske, L
Allergy and asthma proceedings. 2020;(3):183-191
Abstract
Background: The presence of immunoglobulin E (IgE), which cross-reacts with allergen components, such as profilins, polcalcins, and cross-reacting carbohydrate determinants (CCD), creates a problem when selecting patients for allergen immunotherapy by using conventional methods. The aim of this study was to evaluate the prevalence of sensitization to profilins, polcalcins, and CCDs in patients with seasonal pollen allergic rhinitis. Methods: The study was performed on a group of 112 patients with seasonal pollen allergic rhinitis, ages 14 to 55 years, with sensitization to at least one seasonal allergen (IgE > 0.7 kUA/L). The presence of IgE sensitization to recombinant (r) Bet v 2, rPhl p 12, rBet v 4, rPhl p 7, and CCDs, in addition to rBet v 1, rPhl p 1, rPhl p 5, was evaluated by using a multiparameter immunoblot. Results: Among the studied patients, 64.3, 80.4, and 41.1% were sensitized to birch, timothy grass, and mugwort pollen, respectively. Sensitization to profilins rBet v 2/Phl p 12 was demonstrated in 28.6%, to polcalcins Bet v 4/Phl p 7 in 8.9%, and to CCDs in 25%. In 29.3%, serum IgE reactivity to any of the cross-reactive components could be demonstrated. Serum IgE reactivity to rBet v 2 was always accompanied by IgE reactivity to rPhl p 12, and IgE reactivity to rBet v 4 was always accompanied by IgE reactivity to rPhl p 7. Among the patients with pollinosis co-sensitized to at least two allergen sources according to extract-based diagnosis, possible false-positive results due to sensitization to cross-reactive components were detected in 17.9%. Conclusion: Evaluation of sensitization to cross-reacting components may be useful in evaluation of patients with pollen allergy who are being assessed for allergen immunotherapy to optimize the constitution of their immunotherapy vaccines.
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Precision medicine in cow's milk allergy.
D'Auria, E, Venter, C
Current opinion in allergy and clinical immunology. 2020;(3):233-241
Abstract
PURPOSE OF REVIEW The aim of this review is to describe the role of precision medicine in the diagnosis, treatment, and monitoring of cow's milk allergy. RECENT FINDINGS The development of 'omics' sciences in the field of food allergy has led to a better understanding of the allergenicity of cow's milk proteins and significant advances in the knowledge of the pathogenesis and mechanisms of cow's milk allergy. Omics-based technologies allow the practitioner to better differentiate cow's milk allergy subtypes and to predict cow's milk allergy (CMA) persistence over time. Precision medicine extends the role of the oral food challenge, to determine the individual's threshold doses, and to establish tolerance to baked milk products. Other than symptom relief, dietary strategies are currently being investigated for the potential to induce tolerance. Oral immunotherapy offers a treatment option for patients with severe and persistent IgE-mediated CMA. Individual baseline-immune profiles may be predictive of cow's milk oral immunotherapy safety and efficacy.Patient data derived from current technology, in combination with the patient's history, can be translated into treatments targeted at patient-tailored interventions. SUMMARY The identification of novel biomarkers may improve diagnostic accuracy and also predict patient responsiveness to treatments. Integration of patient data will become increasingly important as omics technologies become more widely used in the clinical setting.
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Association of serum 25-OH vitamin D₃ with serum IgE and the Pediatric Asthma Severity Score in patients with pediatric asthma.
Mohammadzadeh, I, Darvish, S, Qujeq, D, Hajiahmadi, M, Vaghari-Tabari, M
Allergy and asthma proceedings. 2020;(2):126-133
Abstract
Background: Pediatric asthma is a prevalent disease and has a significant immunologic and inflammatory nature. In recent years, the role of vitamin D₃ in immunologic processes has been studied, and many aspects of this role have been clarified in some human diseases. Objective: The aim of this study was to evaluate the relationship among the vitamin D₃ status, Pediatric Asthma Severity Score (PASS), and inflammatory indicators of pediatric asthma. Methods: Among all of the pediatric patients with asthma and with asthma exacerbation, 100 patients were randomly enrolled in the study and subdivided into three groups according to serum levels of 25-OH vitamin D₃. The control group consisted of 100 sex- and age-matched healthy subjects. Asthma exacerbation severity was evaluated based on the PASS before starting the medical care. The count of the white blood cells, eosinophil count, and serum levels of total immunoglobulin E (IgE) plus 25-OH vitamin D₃ were measured in all the subjects. The obtained data were then compared via proper statistical tests. A p value of <0.05 was considered as statistically significant. Results: The median level of serum IgE was increased in patients with vitamin D₃ deficiency compared with other groups. There was a significant inverse correlation between serum levels of 25-OH vitamin D₃ and IgE in pediatric patients with asthma (r = -0.483, p = 0.001). Furthermore, the serum levels of 25-OH vitamin D₃ also significantly inversely correlated with the PASS (r = -0.285, p = 0.004). Conclusion: Vitamin D₃ deficiency is associated with exacerbation severity and serum IgE levels in patients with pediatric asthma; hence, it can have an important role in pediatric asthma pathogenesis, possibly through IgE.
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β-1,3-glucanase rOle e 9 and MnSOD rAsp f 6 IgE reactivity are the signature of atopic dermatitis in the Mediterranean area.
Scala, E, Abeni, D, Guerra, EC, Pirrotta, L, Locanto, M, Meneguzzi, G, Giani, M, Russo, G, Asero, R
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2020;(4):487-498
Abstract
BACKGROUND Atopic dermatitis (AD) represents a chronic skin disorder seriously affecting patients' QoL and is often associated with immunological imbalance, disorders of the skin barrier function and environmental factors. OBJECTIVE We extensively studied the proteomic IgE sensitization profile in a large AD Mediterranean cohort. METHODS A total of 588 individuals with moderate-severe (70.6%) or mild and/or history of (29.4%) AD were evaluated in comparison to 1285 unselected atopic controls (AC) with a history of adverse reactions to foods, allergic rhinitis and/or bronchial asthma by means of ImmunoCAP ISAC112 ® and Allergy Explorer-ALEX® microarray analysis. RESULTS The olive tree pollen β-1,3-glucanase rOle e 9 and the manganese superoxide dismutase from Aspergillus rAsp f 6 were the molecules most significantly associated with AD occurrence and allowed to discriminate among the moderate and severe forms of disease. An IgE hyper-reactivity to cypress, grasses, olive tree, house dust mites (including rDer p 11), and to all cross-reactive components except profilin and polcalcin was observed. About 60% of adults with severe AD were sensitized to nsLTPs. Cross-reactive carbohydrate determinants (CCDs) IgE was found in about one-third of AD participants. Hen eggs nGal d 1 IgE sensitization was more prevalent in the paediatric population, whilst rAsp f 6 and rOle e 9 reactivity was found particularly in older patients. Despite the status of widespread IgE sensitization to both environmental and food allergens, a reduced frequency of patient-reported severe reactions to food or of asthma was observed in AD patients compared to AC, particularly in case of concomitant Ole e 9 reactivity. CONCLUSION AND CLINICAL RELEVANCE Testing IgE reactivity to a large panel of molecular components unveils important associations between IgE reactivity profiles and AD clinical presentation, highlights the allergens useful for a precise AD signature and allows the detection of interesting sensitisations patterns.
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IgE-Mediated Food Allergy.
Anvari, S, Miller, J, Yeh, CY, Davis, CM
Clinical reviews in allergy & immunology. 2019;(2):244-260
Abstract
Food allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the immune system, causing a T helper 2 response which results in IgE binding to Fcε receptors on effector cells like mast cells and basophils. The activation of these cells causes release of histamine and other preformed mediators, and rapid symptom onset, in contrast with non-IgE-mediated food allergy which is more delayed in onset. The diagnosis of IgE-mediated food allergy requires a history of classic clinical symptoms and evidence of food-specific IgE by either skin-prick or serum-specific IgE testing. Symptoms of IgE-mediated food allergies range from mild to severe. The severity of symptoms is not predicted by the level of specific IgE or skin test wheal size, but the likelihood of symptom onset is directly related. Diagnosis is excluded when a patient can ingest the suspected food without clinical symptoms and may require an in-office oral food challenge if testing for food-specific IgE by serum or skin testing is negative or low. Anaphylaxis is the most severe form of the clinical manifestation of IgE-mediated food allergy, and injectable epinephrine is the first-line treatment. Management of food allergies requires strict avoidance measures, counseling of the family about constant vigilance, and prompt treatment of allergic reactions with emergency medications. Guidelines have changed recently to include early introduction of peanuts at 4-6 months of life. Early introduction is recommended to prevent the development of peanut allergy. Future treatments for IgE-mediated food allergy evaluated in clinical trials include epicutaneous, sublingual, and oral immunotherapy.
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Ara h 7 isoforms share many linear epitopes: Are 3D epitopes crucial to elucidate divergent abilities?
Ehlers, AM, Klinge, M, Suer, W, Weimann, Y, Knulst, AC, Besa, F, Le, TM, Otten, HG
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2019;(11):1512-1519
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Abstract
BACKGROUND The peanut allergens Ara h 2, h 6, and h 7 are potent allergens and can trigger severe reactions. Ara h 7 consists of three isoforms differing in their ability to induce basophil degranulation, whereas the ability of Ara h 7.0201 is comparable to Ara h 2 and 6 as shown in previous literature. OBJECTIVE To identify linear epitopes of Ara h 7.0101, Ara h 7.0201 and Ara h 7.0301 recognized by IgE and IgG4 from patients sensitized to Ara h 7 and to investigate their potential to elucidate divergent abilities of the Ara h 7 isoforms in inducing basophil activation. METHODS Linear epitopes recognized by IgE and IgG4 were mapped by peptide microarray analysis containing 15-mer peptides of Ara h 2.0201, 6, 7.0101, 7.0201 and 7.0301 and 39 peanut allergic patients sensitized to Ara h 7 (discovery). For validation, 20-mer peptides containing the minimal epitope and surrounding amino acids were incubated with 25 sensitized patients and 10 controls (validation). RESULTS Three out of 14 linear epitopes were unique for each isoform (Ara h 7.0101: aa 97-109; Ara h 7.0201: aa 122-133; Ara h 7.0301: aa 65-74) but scarcely recognized by IgE. The main linear IgE epitope (aa 51-57) located in the long flexible loop of all Ara h 7 isoforms was bound by antibodies from 31% of the patients (discovery and validation cohort). Regarding IgG4, 55% of the patients recognized an epitope present on all isoforms (aa 55-65), whereas epitope aa 129-137, only present on Ara h 7.0101/0.0301, was recognized by 38% of the patients. Recognition was highly individual, although 20% of the patients recognized any linear epitope neither by IgE nor by IgG4 despite a low mean z-score of ≥ 1.7. Remarkably, only 50% of the patients recognized one or more epitopes by IgE. CONCLUSION & CLINICAL RELEVANCE Ara h 7 isoforms share many linear epitopes being easily accessible for antibody binding. Unique epitopes, essential to elucidate divergent potencies, were scarcely recognized, suggesting a crucial involvement of conformational epitopes.
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Molecular Approaches for Diagnosis, Therapy and Prevention of Cow´s Milk Allergy.
Linhart, B, Freidl, R, Elisyutina, O, Khaitov, M, Karaulov, A, Valenta, R
Nutrients. 2019;(7)
Abstract
Cow´s milk is one of the most important and basic nutrients introduced early in life in our diet but can induce IgE-associated allergy. IgE-associated allergy to cow´s milk can cause severe allergic manifestations in the gut, skin and even in the respiratory tract and may lead to life-threatening anaphylactic shock due to the stability of certain cow´s milk allergens. Here, we provide an overview about the allergen molecules in cow´s milk and the advantages of the molecular diagnosis of IgE sensitization to cow´s milk by serology. In addition, we review current strategies for prevention and treatment of cow´s milk allergy and discuss how they could be improved in the future by innovative molecular approaches that are based on defined recombinant allergens, recombinant hypoallergenic allergen derivatives and synthetic peptides.