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1.
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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2.
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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Eosinophilic Esophagitis: Personalized Treatment With an Elimination Diet Based on IgE Levels in Children Aged <16 Years.
Gómez Torrijos, E, Moreno Lozano, L, Extremera Ortega, AM, González Jimenez, OM, Mur Gimeno, P, Borja Segade, JM, Alfaya Arias, T, García Rodríguez, R
Journal of investigational allergology & clinical immunology. 2019;(2):155-157
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Epigenetic features of FoxP3 in children with cow's milk allergy.
Paparo, L, Nocerino, R, Cosenza, L, Aitoro, R, D'Argenio, V, Del Monaco, V, Di Scala, C, Amoroso, A, Di Costanzo, M, Salvatore, F, et al
Clinical epigenetics. 2016;:86
Abstract
BACKGROUND DNA methylation of the Th1 and Th2 cytokine genes is altered during cow's milk allergy (CMA). Forkhead box transcription factor 3 (FoxP3) is essential for the development and function of regulatory T cells (Tregs) and is involved in oral tolerance acquisition. We assessed whether tolerance acquisition in children with IgE-mediated CMA is associated with DNA demethylation of the Treg-specific demethylated region (TSDR) of FoxP3. RESULTS Forty children (aged 3-18 months) were enrolled: 10 children with active IgE-mediated CMA (group 1), 10 children who outgrew CMA after dietary treatment with an extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG (group 2), 10 children who outgrew CMA after treatment with other formulas (group 3), and 10 healthy controls (group 4). FoxP3 TSDR demethylation and expression were measured in mononuclear cells purified from peripheral blood of the four groups of children. FoxP3 TSDR demethylation was significantly lower in children with active IgE-mediated CMA than in either children who outgrew CMA or in healthy children. Formula selection influenced the FoxP3 TSDR demethylation profile. The FoxP3 TSDR demethylation rate and expression level were correlated. CONCLUSIONS Tolerance acquisition in children with IgE-mediated CMA involves epigenetic regulation of the FoxP3 gene. This feature could be a new target for preventive and therapeutic strategies against CMA.
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The diagnostic value of component-resolved diagnostics in peanut allergy in children attending a Regional Paediatric Allergology Clinic.
van Veen, LN, Heron, M, Batstra, M, van Haard, PMM, de Groot, H
BMC pediatrics. 2016;:74
Abstract
BACKGROUND To date, diagnosing food allergies in children still presents a diagnostic dilemma, leading to uncertainty concerning the definite diagnosis of peanut allergy, as well as to the need for strict diets and the potential need for adrenalin auto-injectors. This uncertainty in particular is thought to contribute to a lower quality of life. In the diagnostic process double-blind food challenges are considered the gold standard, but they are time-consuming as well as potentially hazardous. Other diagnostic tests have been extensively studied and among these component-resolved diagnostics appeared to present a promising alternative: Ara h2, a peanut storage protein in previous studies showed to have a significant predictive value. METHODS Sixty-two out of 72 children, with suspected peanut allergy were analyzed using serum specific IgE and/or skin prick tests and specific IgE to several components of peanut (Ara h 1, 2, 3, 6, 8, 9). Subsequently, double-blind food challenges were performed. The correlation between the various diagnostic tests and the overall outcome of the double-blind food challenges were studied, in particular the severity of the reaction and the eliciting dose. RESULTS The double-blind provocation with peanut was positive in 33 children (53 %). There was no relationship between the eliciting dose and the severity of the reaction. A statistically significant relationship was found between the skin prick test, specific IgE directed to peanut, Ara h 1, Ara h 2 or Ara h 6, and the outcome of the food challenge test, in terms of positive or negative (P < .001). However, we did not find any relationship between sensitisation to peanut extract or the different allergen components and the severity of the reaction or the eliciting dose. There was no correlation between IgE directed to Ara h 3, Ara h 8, Ara h 9 and the clinical outcome of the food challenge. CONCLUSIONS This study shows that component-resolved diagnostics is not superior to specific IgE to peanut extract or to skin prick testing. At present, it cannot replace double-blind placebo-controlled food challenges for determination of the eliciting dose or the severity of the peanut allergy in our patient group.
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Total IgE at 6 months predicts remittance or persistence of atopic dermatitis at 14 months.
Kawamoto, N, Fukao, T, Kaneko, H, Hirayama, K, Sakurai, S, Arai, T, Kondo, M, Kawamoto, M, Matsui, E, Orii, K, et al
Allergy and asthma proceedings. 2013;(4):362-369
Abstract
Some patients with infantile atopic dermatitis (AD) achieve remission around 1 year old, but in others it persists. The difference between them is unclear. We performed a birth cohort study to find the markers predicting the outcome of infantile AD. We followed up a cohort (n = 314) from birth to 14 months of age, and cord blood was taken from the participants. Some of them (n = 144) had a physical examination and a blood test at 6 and 14 months of age. The subjects who had AD at 6 months (n = 34) were divided into two groups, named the transient group (those who had no AD at 14 months of age; n = 16) and the persistent group (those who still had AD at 14 months of age; n = 18). Then, laboratory data were compared between these two groups. Percentage of CD8 in cord blood lymphocytes and total IgE at 6 months of age in the persistent group was significantly higher than those of the transient group. The area under the curves of a receiver operating characteristic analysis were 0.792 (p = 0.007) and 0.722 (p = 0.027). In the persistent group, total IgE, percentages of T-helper (Th) 2 and phytohemagglutinin-induced IL-4 production from peripheral blood mononuclear cells at 14 months of age were also significantly higher than those of the transient group. Thus Th2 polarization in the persistent group was confirmed. In clinical use, total IgE at 6 months of age is the most useful predictive marker to know the outcome of infantile AD. The clinical trial registration ID is UMIN000002926.
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Serum IgG, IgA, IgM, and IgE levels after electroacupuncture and diet therapy in obese women.
Cabioglu, MT, Ergene, N, Surucu, HS, Celik, HH, Findik, D
The American journal of Chinese medicine. 2007;(6):955-65
Abstract
We investigated the effect of acupuncture therapy on obese women's body weight and peripheral blood levels of serum immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin E (IgE). Sixty-three healthy women were assigned into 3 groups: placebo electroacupuncture (n = 13; mean age, 40.5 +/- 4.2 years; body mass index [BMI], 33.5 +/- 4.2), diet restriction (n = 23; mean age, 42.9 +/- 4.0 years; BMI, 34.6 +/- 2.9), and electroacupuncture (n = 24; mean age, 40.1 +/- 5.9 years; BMI, 33.9 +/- 2.7). Electroacupuncture was applied to the Hunger and Shen Men ear points and to the LI 4, LI 11, St 36, St 44, and Ren 6 body points for 30 min once daily for 20 days. A restricted diet of 1400 kilocalories was given to participants in all 3 groups for 20 days. Weight was lost significantly in subjects in the electroacupuncture group compared to those in the diet restriction and placebo electroacupuncture groups (p < 0.000, Tukey test). Modulations in serum IgG (p < 0.001) were apparent in women treated with electroacupuncture compared with women treated with placebo electroacupuncture and restricted diet only. No significant changes were seen in serum IgA, IgM, and IgE levels among the 3 groups. Our results suggest that electroacupuncture can be effectively used to treat obesity. We also observed a modulating effect of serum IgG, which is associated with weight loss, in patients in the electroacupuncture group.
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Preliminary human study for possible alteration of serum immunoglobulin E production in perennial allergic rhinitis with fermented milk prepared with Lactobacillus gasseri TMC0356.
Morita, H, He, F, Kawase, M, Kubota, A, Hiramatsu, M, Kurisaki, J, Salminen, S
Microbiology and immunology. 2006;(9):701-6
Abstract
The fermented milk prepared with Lactobacillus gasseri TMC0356 was administered at 200 ml per day for 4 weeks to 15 subjects with high serum IgE levels and perennial allergic rhinitis. The serum total IgE concentration was significantly reduced after 28 days' exposure to the fermented milk (P <0.05) compared to that before the intervention. The serum IgE specific to Acari and those to Japanese cedar pollen also significantly declined (P <0.05). T helper 1 (Th1) cells in the composition of their peripheral blood mononuclear cells (PBMCs) significantly increased after 14 days (P <0.01) and after 28 days (P <0.05). These results suggest that the fermented milk prepared with L. gasseri TMC0356 may alter serum IgE concentration, at least partly by enhancement of Th1 immune responses of the subjects with high concentration of serum IgE. However, further studies are still necessary to know the underlying mechanisms by which the tested fermented milk could influence the host immunity.
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The effect of montelukast and different doses of budesonide on IgE serum levels and clinical parameters in children with newly diagnosed asthma.
Stelmach, I, Bobrowska-Korzeniowska, M, Majak, P, Stelmach, W, Kuna, P
Pulmonary pharmacology & therapeutics. 2005;(5):374-80
Abstract
BACKGROUND Since IgE is considered to play a crucial role in allergic immune responses, the reduction of free IgE level has been an attractive target in the treatment of allergic diseases. The present study was conducted to determine the effects of a 6-month treatment with different doses of inhaled budesonide and montelukast sodium in children with newly diagnosed atopic asthma. METHODS In this randomized, double-blind, double-dummy trial, 51 children with newly diagnosed asthma and sensitivity to house-dust mites were randomly allocated to receive budesonide (in two different doses 400 or 800 mcg) or montelukast for 6 months. The primary end point was the level of serum total and specific IgE before and after treatment. The secondary end points were clinical parameters and forced expiratory volume in 1s (FEV1). RESULTS After 6 months of treatment, a high dose of inhaled corticosteroid and montelukast, significantly decreased levels of total and specific IgE. Medium dose of inhaled corticosteroid had no effect on total and specific IgE serum level. Clinical score and FEV1 significantly improved after 6 months of treatment with medium (P = 0.002) and high dose (P = 0.001) of inhaled budesonide and montelukast (P = 0.002). There were no differences between groups in changes of all clinical parameters after treatment. CONCLUSION Only high doses of inhaled corticosteroids and montelukast decreased the serum IgE levels. Perhaps long-term treatment with montelukast will be beneficial to asthma patients by decreasing IgE levels.
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Specific IgE levels do not indicate persistence or transience of food allergy in children with atopic dermatitis.
Niggemann, B, Celik-Bilgili, S, Ziegert, M, Reibel, S, Sommerfeld, C, Wahn, U
Journal of investigational allergology & clinical immunology. 2004;(2):98-103
Abstract
BACKGROUND Food allergy in early childhood usually resolves with time; however, little is known about predictors for persistence or transience of food allergy in children with atopic dermatitis. The aim of the study was to evaluate whether specific IgE levels in serum could be a useful predictor of the outcome of oral re-challenges. METHODS In 74 children, 99 oral food challenges were performed (cow milk n = 48, hen egg n = 37, and wheat n = 14) and repeated after a median time interval of 16 months. In 15 of the 74 children, a third challenge (n = 22) could be performed, with a median time interval from second challenge to third challenge of 15 months. RESULTS There were 37 children with transient food allergy (positive first challenge and negative second challenge), while 62 children had persistent food allergy (positive first challenge and negative second challenge). Comparison of the two groups showed that specific IgE as well as total IgE in serum was significantly higher in the latter group. However, looking at the time course, specific IgE did not decrease significantly during elimination diet. CONCLUSION Our results indicate that specific IgE in serum--although very helpful at the time of the first diagnosis--cannot predict whether a chid will become tolerant after a period of avoidance. Therefore, oral re-challenges remain mandatory.