Presence Of Allergen-specific IgE Research Articles

Metabolomics identifies phenotypic biomarkers of amino acid metabolism in milk allergy and sensitized tolerance

BackgroundA substantial proportion of sensitized individuals tolerate suspected foods without developing allergic symptoms; this phenomenon is known as sensitized tolerance. The immunogenic and metabolic features underlying the sensitized-tolerant phenotype remain largely unknown. ObjectiveIn this study, we aimed to uncover the metabolic signatures associated with clinical milk allergy and sensitized tolerance using metabolomics. MethodsWe characterized the serum metabolic and immunological profiles of children with clinical IgE-mediated milk allergy (MA; n = 30) or milk-sensitized tolerance (MST; n = 20) and healthy controls (n = 21). A comparative analysis was performed to identify dysregulated pathways associated with the clinical manifestations of food allergy. We also analyzed specific biomarkers indicative of different sensitization phenotypes in children with MA. The candidate metabolites were validated in an independent quantification cohort (n = 41). ResultsMetabolomic profiling confirmed the presence of a distinct metabolic signature that discriminated children with MA from those with MST. Amino acid metabolites generated via arginine, proline, and glutathione metabolism were uniquely altered in children with sensitized tolerance. Arginine depletion and metabolism through the polyamine pathway to fuel glutamate synthesis were closely associated with the suppression of clinical symptoms in the presence of allergen-specific IgE. In children with MA, the polysensitized state was characterized by disturbances in tryptophan metabolism. ConclusionsBy combining untargeted metabolomics with targeted validation in an independent quantification cohort, we identified candidate metabolites as phenotypic and diagnostic biomarkers of food allergy. Our results provide insights into the pathological mechanisms underlying childhood allergy and suggest potential therapeutic targets.

Efficacy Of Tezepelumab In Patients With Severe, Uncontrolled Asthma By Specific Perennial Allergen Immunoglobulin E Thresholds

Allergic asthma is the most common type of asthma. The presence of allergen-specific IgE is synonymous with sensitization to that allergen, and often correlates with perennial allergy. A threshold of ≥0.35 kUA/L is generally used to define a positive result, but higher concentrations may indicate a greater degree of sensitivity. Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. This post hoc analysis evaluated the efficacy of tezepelumab, using pooled data from phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, in patients with perennial allergy grouped by different thresholds of serum specific IgE.

Extract-Shaped Immune Repertoires as Source for Nanobody-Based Human IgE in Grass Pollen Allergy.

The presence of allergen-specific IgE in serum is a biomarker for allergic disease. Specific IgE antibodies for research and diagnostics, however, remain scarce. In contrast to prototypic antibodies, camelid species have evolved single domains as moiety for antigen recognition. These so-called nanobodies represent a versatile platform for the development of diagnostic and therapeutic approaches. In this study, we aimed for generating nanobodies and derived IgE formats from an extract-shaped immune repertoire. Timothy grass pollen represents a complex, but well-defined mixture of individual allergens. Therefore, a repertoire library from a timothy grass pollen extract immunised llama was established. The selection by phage display yielded 3 nanobodies with immunoreactivity to the extract. IgE-like nanobody-based human IgE (nb-hIgE) antibodies were produced in mammalian cells and assessed in different immunoassays and commercial platforms. Immunoblotting and diagnostic ImmunoCap analysis of single timothy grass pollen allergens identified the major allergens Phl p 6 and Phl p 4 as targets. Assessment of immunoreactivity further documented significant molecular cross-reactivity with pollen extract of different grass species and variant presence of allergens within extracts of Pooideae grasses. In summary, our study shows that extract-based immunisation enables the generation of allergen-specific nanobodies and derived nb-hIgE formats linking nanobody technologies with allergological applications.

Use of Humanized Fluorescent Reporter Cell Line RBL NFAT-DsRed for the Detection of Allergen-Specific IgE in Patient Sera Using Allergen Microarrays.

The presence of allergen-specific IgE (sIgE) in human sera can be determined by measuring the binding of sIgE to solid phase-bound preparations containing the allergens to be tested. These can be complex extracts, purified or recombinant allergens, or peptides. Older methods, such as the IgE CAP test, only allow sIgE measurements to multiple allergens in individual measurements. Newer technologies such as the ImmunoCAP® ISAC test allows semiquantitative testing of sIgE to over a hundred allergens on a protein array. Allergen arrays have higher numerical power, allowing testing to many allergens at the same time, using only a small amount of serum. We have previously demonstrated how allergen arrays can be used in combination with purified peripheral blood basophils, introducing a clinically relevant readout. Here, we describe a protocol and materials that allow the testing of sIgE with multiple allergens in array format, using a humanized fluorescent IgE reporter system (RBL NFAT-DsRed).

Aetiology of anaphylaxis in patients referred to an immunology clinic in Colombo, Sri Lanka

BackgroundThe aetiology of anaphylaxis differs according to types of foods consumed, fauna and foliage and cultural practices. Although the aetiology of anaphylaxis in Western countries are well known, the causes in South Asian countries have not been reported. We sought to determine the causes of anaphylaxis in patients referred to an immunology clinic in Colombo, Sri Lanka.Methods238 episodes of anaphylaxis were reviewed in 188 patients who were referred and skin prick tests and in vitro tests (ImmunoCap) were carried out to assess the presence of allergen specific IgE. Clinical features and severity of anaphylaxis was also recorded along with treatment received.ResultsAnaphylaxis to food either following direct exposure 90/238 (37.5%) or after exercise in the form of food dependent exercise induced anaphylaxis 29/238 (12.2%) was the predominant cause of anaphylaxis. Allergy to cow’s milk and red meat, after immediate exposure, accounted for 66/238 (27.7%) of instances of all episodes of anaphylaxis and 66/90 (73.33%) of anaphylaxis due to food. Vaccines accounted for 28/238 (11.8%) of instances of anaphylaxis, especially among children. Of those who developed anaphylaxis to the MMR (n = 14), 71.4% of them had specific IgE to cow’s milk and 35.7% of them had specific IgE to beef. Of those who developed anaphylaxis to insect stings, 27/42 of these episodes occurred following stings of ants (family Formicidae). The predominant cause of anaphylaxis changed with the age, with food allergy being the most frequent trigger of anaphylaxis in childhood, while drug allergy and idiopathic anaphylaxis being more frequent after 30 years of age.ConclusionsIn this cohort, anaphylaxis to red meat appears to be the predominant cause of food induced anaphylaxis and presence of beef specific IgE and cow’s milk, appears to be a predisposing factor for vaccine induced anaphylaxis.

Recent advances in allergic rhinitis.

Allergic rhinitis affects 20 to 30% of adults in both the United States and Europe and perhaps a somewhat higher percentage of children. In addition to nasal and ocular symptoms directly related to the allergic process, interference of these symptoms with sleep leads to daytime sleepiness and impaired quality of life. Patients miss work because of symptoms but an even greater problem is interference with work productivity, or presenteeism, which has been reported to be the biggest contributor to the total economic cost of allergic rhinitis. There has been increasing awareness that many patients with either seasonal or perennial symptoms but negative skin and in vitro tests for allergen sensitivity have local nasal allergy, diagnosable by the presence of allergen-specific IgE in their nasal secretions or a positive nasal allergen challenge or both. The pharmaceutical management of allergic rhinitis rests on symptomatic treatment with antihistamines that perhaps are more effectively administered intranasally than orally and intranasal corticosteroids. Allergen immunotherapy is very effective, even for local allergic rhinitis, and the shortcomings of subcutaneous immunotherapy of inconvenience and safety are reduced by the introduction of sublingual immunotherapy (SLIT). Use of the latter is currently somewhat limited by the lack of appropriate dosing information for SLIT liquids and the limited number of allergens for which SLIT tablets are available.

Association of Macrophage Migration Inhibitory Factor Polymorphisms with Total Plasma IgE Levels in Patients with Atopic Dermatitis in Korea.

The macrophage migration inhibitory factor (MIF) gene is located on human chromosome 22q11.2 and is linked to atopic phenotypes. Plasma MIF and log [total IgE] levels are significantly elevated in atopic dermatitis (AD) patients. The aim of this study was to evaluate the relationship between two MIF polymorphisms, −173 G to C and −794 CATT5–8, and total plasma IgE levels in AD patients in Korea. We performed PCR-RFLP analysis in 178 AD patients and 80 control subjects to determine whether MIF SNPs are associated with susceptibility to AD. Plasma total IgE and MIF levels were determined, and then logistic regression analyses were performed to determine the associations between a SNP or haplotype and plasma total IgE or MIF levels. The −173 G/C polymorphism, located in the MIF promoter, was significantly associated with AD; the odds ratios (ORs) for the CC homozygotes and GC heterozygotes were 9.3 and 2.5, respectively. The MIF C/5-CATT and the MIF C/7-CATT haplotypes were significantly associated with AD; the ORs for the MIF C/5-CATT and MIF C/7-CATT haplotypes were 9.7 and 4.5, respectively. Log [total IgE] levels were highly associated with the MIF −794 7-CATT polymorphism. Notably, the MIF C/7-CATT haplotype was associated with a decrease in plasma log [total IgE] levels in a gene dose-dependent manner. Although log [MIF] levels were not associated with the MIF polymorphisms, the frequencies of the MIF C/5-CATT haplotype-containing genotypes decreased in order of MIF levels. Our results demonstrate that MIF promoter polymorphisms in the −173 C allele and the MIF C/5-CATT and C/7-CATT haplotypes were significantly associated with an increased risk for AD. In particular, the −794 7-CATT locus and the MIF C/7-CATT haplotype were significantly associated with decreased total IgE levels in the plasma, suggesting that these polymorphisms might be a marker for intrinsic AD rather than extrinsic AD that shows high total IgE levels and presence of allergen-specific IgE.

Mouse Models ofAsthma.

Allergic asthma is a chronic inflammatory disease of the conducting airways characterized by the presence of allergen-specific IgE, Th2 cytokine production, eosinophilic airway inflammation, bronchial hyperreactivity, mucus overproduction, and structural changes in the airways. Investigators have tried to mimic these features of human allergic asthma in murine models. Whereas the surrogate allergen ovalbumin has been extremely valuable for unravelling underlying mechanisms of the disease, murine asthma models depend nowadays on naturally occurring allergens, such as house dust mite (HDM), cockroach, and Alternaria alternata. Here we describe a physiologically relevant model of acute allergic asthma based on sensitization and challenge with HDM extracts, and compare it with the ovalbumin/alum-induced asthma model. Moreover, we propose a detailed readout of the asthma phenotype, determining the degree of eosinophilia in bronchoalveolar lavage fluids by flow cytometry, visualizing goblet cell metaplasia, and measuring Th cytokine production by lung-draining mediastinal lymph node cells restimulated with HDM. © 2016 by John Wiley & Sons, Inc.

Under-Recognized Effects of Allergic Disorders on Neuropsychiatric Symptoms, in Subjects with Limited Expressive Language

Diagnosis of allergic diseases are based on detailed clinical history and careful physical examinations supported by skin test (ST) reactivity and/or presence of allergen specific IgE in the serum for IgE-mediated allergy. Clinicians tend to focus on clinical manifestations that occur in the organs affected directly by allergen exposure. However, many epidemiological studies support a positive association between neuropsychiatric symptoms and allergic diseases, although in most epidemiological studies, allergy diagnoses are based on self-reported survey results and/or billing codes. With current diagnostic tools heavily relying on clinical history, individuals with limited expressive language (LEL) imposes a significant challenge for practicing clinicians. LEL subjects also often exhibit neuropsychiatric symptoms associated with their primary medical conditions. In such subjects, it is often very difficult to differentiate neuropsychiatric symptoms associated with pain and discomfort caused by allergic diseases from those caused by their primary medical conditions. In addition, lack of appreciation of their allergic conditions by the care-givers may further frustrate LEL subjects, rendering worsening their behavioral symptoms. This review was formulated to address the association between neuropsychiatric symptoms and allergic disorders, emphasizing the need for the special attention required when evaluating LEL subjects for allergic diseases. Since many allergic diseases are relatively easily treatable with benign medications, clinicians need to carefully evaluate and treat common allergy conditions in LEL subjects, especially prior to treating them with neurotropic medications, which likely cause more undesirable side effects.

Study of Toxocara seroprevalence among patients with allergy and healthy individuals in Bulgaria.

Data in the literature addressing the ability of Toxocara infection in humans to induce development of atopic disease are controversial. The aim of our study was to determine the seroprevalence of anti-Toxocara antibodies in three groups of people: subjects with allergic symptoms and presence of allergen-specific IgE, subjects with allergic symptoms and absence of allergen-specific IgE, and clinically healthy blood donors. Serum samples from all subjects were tested by ELISA and Western blot for presence of specific antibodies against Toxocara canis. The results of our study did not support the link between toxocariasis and allergic manifestations in atopic patients. Among subjects with allergic symptoms and absence of atopy was found seroprevalence of 2·2% in Western blot. Same index in patients with atopy was 0·8%, and in clinically healthy blood donors 4·0%. Our study gives us grounds to consider that it is appropriate persons with allergic reactions, without evidence of atopy to be tested for presence of anti-Toxocara antibodies in the course of their diagnostic evaluation. Data from clinically healthy persons suggest that there is a 'hidden' infection among the population, which is not clinically manifested.

Serum MicroRNA-21 as a Biomarker for Allergic Inflammatory Disease in Children.

MicroRNAs (miRs) have emerged as useful biomarkers for different disease states, including allergic inflammatory diseases such as asthma and eosinophilic esophagitis (EoE). Serum miRs are a possible non-invasive method for diagnosis of such diseases. We focused on microRNA-21 (miR-21) levels in serum, in order to assess the feasibility of using this gene as a non-invasive biomarker for these diseases in the clinic, as well as to better understand the expression pattern of miR-21 in allergic inflammation. We used quantitative PCR (QPCR) to assay miR-21 and other control miRs in esophageal biopsies from EoE patients and serum samples from EoE and asthma patients. Serum levels of miR-21 were significantly elevated in patients with asthma, whereas serum miR-21 levels were not associated with the presence of allergen-specific IgE (i.e. atopy). Esophageal biopsies showed a large elevation of miR-21 in EoE and an increase in miR-21 in EoE serum. Control U6 miR did not vary between asthma and control patients, however EoE serum had significantly decreased U6 microRNA compared to controls. The decreased U6 in EoE sera did not completely account for the relative increase in miR-21 in the sera of EoE patients. We report for the first time that miR-21 is elevated in the sera of both asthma and EoE patients. We find no relation between serum miR-21 levels and atopy. Our results thus suggest miR-21 is a novel biomarker for human allergic inflammatory diseases.

Transmission of allergen-specific IgG and IgE from maternal blood into breast milk visualized with microarray technology

Transmission of allergen-specific IgG and IgE from maternal blood into breast milk visualized with microarray technology

High proportions of FOXP3+CD25high T cells in neonates are positively associated with allergic sensitization later in childhood

BackgroundThe role of FOXP3+ regulatory T cells in the prevention against sensitization and allergy development is controversial.ObjectiveWe followed 65 newborn Swedish children from farming and non-farming families from birth to 3 years of age and investigated the relation between CD4+ T cell subsets in blood samples and development of sensitization and allergic disease.MethodsThe proportions of FOXP3+CD25high, CTLA-4+CD25+, CD45RO+, HLA-DR+, CCR4+ or α4β7+ within the CD4+ T cell population were examined by flow cytometry of blood samples at several time-points. Mononuclear cells were isolated from blood and stimulated with birch allergen, ovalbumin or the mitogen PHA, and the levels of IL-1β, IL-6, TNF, IFN-γ, IL-5 and IL-13 were measured. A clinical evaluation regarding the presence of allergen-specific IgE and allergy was performed at 18 and 36 months of age.ResultsMultivariate discriminant analysis revealed that children who were sensitized at 18 or 36 months of age had higher proportions of FOXP3+CD25high T cells at birth and at 3 days of life than children who remained non-sensitized, whereas allergy was unrelated to the neonatal proportions of these cells. The proportions of CTLA-4+CD25+ T cells were unrelated to both sensitization and allergy. The association between higher proportions of FOXP3+CD25high T cells and sensitization persisted after exclusion of farmer's children. Finally, a farming environment was associated with lower proportions of FOXP3+CD25high T cells in early infancy and to a more prominent T cell memory conversion and cytokine production.Conclusion & Clinical RelevanceOur results indicate that high proportions of FOXP3+CD25high T cells in neonates are not protective against later sensitization or development of allergy.

Diagnosis of Allergic Rhinitis

Rhinitis is divided into allergic and non-allergic rhinitis. Non-allergic rhinitis includes inflammatory rhinitis, such as non-allergic rhinitis with eosinophilia syndrome (NARES) and infective rhinitis, and non-inflammatory rhinitis, such as vasomotor rhinitis and idiopathic rhinitis. Allergic rhinitis is diagnosed based on the presence of allergen-specific IgE and the documentation of relationship between the allergen and symptoms in patients with typical rhinitis symptoms, such as rhinorrhea, nasal obstruction, itchiness and/or sneezing. Local allergic rhinitis can be considered for differential diagnosis. Allergic rhinitis should be differentiated from non-allergic rhinitis by using skin prick test, serum specific IgE test, nasal cytology and/or allergen nasal provocation test. Allergic rhinitis should be differentiated from structural nasal diseases, such as septal deviation and nasal polyps. Rhinitis is frequently accompanied by paranasal sinusitis, which should be recognized in clinical practice. Management strategies differ between allergic and nonallergic rhinitis. In addition to pharmacotherapy, allergen avoidance and allergen-specific immunotherapy can be tried in patients with allergic rhinitis. Thus, the exact diagnosis is very important for the effective treatment in allergic rhinitis. The diagnostic tests for allergic rhinitis are reviewed. (Korean J Med 2013,85:452-456)

Effects of geohelminth infection and age on the associations between allergen‐specific IgE, skin test reactivity and wheeze: a case‐control study

BackgroundMost childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age.ObjectiveTo explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze.MethodsA case-control study was done in 376 subjects (149 cases and 227 controls) aged 7–19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma.ResultsThe fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33–3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49–11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections.Conclusions and clinical relevanceAtopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation.

Metabolic activity of neutrophilic granulocytes measured with chemiluminescence test (cl) in patients with allergic hypersensitivity to food

Introduction. Neutrophilic granulocytes (neutrophils) are the most important cells of non-specific immune response. These cells have capability of chemotaxis and phagocytosis and also participate in inflammatory processes. Stimulated neutrophils release reactive oxygen species (ROS) important mediators of inflammatory process responsible for tissues injury. The aim of the study was assessment of oxygenic metabolism as one of representatives regarding metabolic activity of neutrophilic granulocytes measured with chemiluminescence test (CL) in patients with allergic type of hypersensitivity to food. Material and methods. The study contained 30 patients with diagnosed food allergy on the base of medical history, clinical symptoms, positive prick tests and the presence of allergen-specific IgE against selected food allergens in the serum. The control group contained 10 healthy volunteers. Chemiluminescence of basal and stimulated during 40 minutes neutrophils (fMLP, PMA, OZ) was assessed with kinetic luminol-dependent method using luminometer LUMINOSCAN - LABSYSTEM. Results. Mean values of obtained chemiluminescence from basal and stimulated neutrophils were statistically significantly higher in patients with allergic hypersensitivity to food than values in group of healthy persons. Conclusions. The results of performed analyses indicate that neutrophils participate and have increased activity in the process of allergic inflammation in patients with food allergy.

P2-198 Overweight associated with non-atopic wheeze in rural tropics

IntroductionThe parallel rise in prevalence of asthma and overweight/obesity in some Latin American countries has led to suggestions of a link between the two epidemics. The aim of this study...

Chronic virus infections supress atopy but not asthma in a set of children from a large latin american city: a cross-section study

BackgroundThe prevalence of allergic diseases has increased over recent decades in affluent countries, but remains low in rural populations and some non-affluent countries. An explanation for these trends is that increased exposure to infections may provide protection against the development of allergy. In this work we investigated the association between exposure to viral infections in children living in urban Brazil and the prevalence of atopy and asthma.MethodsSchool age children living in poor neighborhoods in the city of Salvador were studied. Data on asthma symptoms and relevant risk factors were obtained by questionnaire. Skin prick tests (SPTs) were performed to seven aeroallergens, and specific IgE was measured to four of these. Viral infections were determined by the presence of specific IgG in serum to Herpes simplex (HSV), Herpes zoster (HZV), Epstein-Barr (EBV), and Hepatitis A (HAV) viruses.ResultsA total of 644 (49.7%) children had at least one allergen-specific IgE> 0.35 kU/L and 489 (37.7%) had specific IgE> 0.70 kU/L. A total of 391 (30.2%) children were skin test positive (SPT+), and 295 (22.8%) children were asthmatic. The seroprevalence of viral infections was 88.9% for EBV, 55.4% for HSV, 45.5% for VZV and 17.5% for HAV. Negative associations were observed between SPT+ and HSV (OR = 0.64, CI = 0.51, 0.82) and EBV (OR = 0.63, CI = 0.44, 0.89) infections, but no associations were seen between viral infections and the presence of allergen-specific IgE or asthma.ConclusionThese data do not support previous data showing a protective effect of HAV against atopy, but did show inverse associations between SPT+ (but not specific IgE+) and infections with HSV and EBV. These findings suggest that different viral infections may protect against SPT+ in different settings and may indicate an immunoregulatory role of such infections on immediate hypersensitivity responses. The data provide no support for a protective effect of viral infections against asthma in this population.

Mesenteric lymph node transcriptome profiles in BALB/c mice sensitized to three common food allergens

BackgroundFood allergy is a serious health concern among infants and young children. Although immunological mechanism of food allergy is well documented, the molecular mechanism(s) involved in food allergen sensitization have not been well characterized. Therefore, the present study analyzed the mesenteric lymph node (MLN) transcriptome profiles of BALB/c mice in response to three common food allergens.ResultsMicroarray analysis identified a total of 1361, 533 and 488 differentially expressed genes in response to β-lactoglobulin (BLG) from cow's milk, ovalbumin (OVA) from hen's egg white and peanut agglutinin (PNA) sensitizations, respectively (p < 0.05). A total of 150 genes were commonly expressed in all antigen sensitized groups. The expression of seven representative genes from microarray experiment was validated by real-time RT-PCR. All allergens induced significant ear swelling and serum IgG1 concentrations, whereas IgE concentrations were increased in BLG- and PNA-treated mice (p < 0.05). Treatment with OVA and PNA significantly induced plasma histamine concentrations (p < 0.05). The PCA demonstrated the presence of allergen-specific IgE in the serum of previously sensitized and challenged mice.ConclusionsImmunological profiles indicate that the allergen dosages used are sufficient to sensitize the BALB/c mice and to conduct transcriptome profiling. Microarray studies identified several differentially expressed genes in the sensitization phase of the food allergy. These findings will help to better understand the underlying molecular mechanism(s) of food allergen sensitizations and may be useful in identifying the potential biomarkers of food allergy.

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report