Exposure to farm environment and its correlations with total IgE, IL-13, and IL-33 serum levels in patients with atopy and asthma

Background: The aim of the study was to evaluate total immunoglobulin E (IgE), IL-13, and IL-33 serum level in people with bronchial asthma and atopy, and in healthy control group depending on their exposure to farm animals currently and in the first year of life. Methods: The study included 174 individuals living in rural areas and in a small town. Standardized questions from the International Study of Asthma and Allergy in Childhood and The European Community Respiratory Health Survey (ECRHS) questionnaires were used to define asthma. Atopic status was verified by skin prick tests. Rural exposure including contact with livestock was verified by adequate questionnaire. Total serum IgE, IL-13, and IL-33 levels were assessed by ELISA (enzyme-linked immunosorbent assay) tests. Results: Participants with atopy and bronchial asthma were characterized by high level of immunoglobulin E. Tendency to lower serum IgE level was observed among people reporting present contact with farm animals. Also, among those having contact with livestock in their first year of life, the analogous tendency was noticed. No difference in serum IL-13 levels in participants with asthma and atopy, and controls was observed, and there was no effect of exposure on farm animals on the concentration of IL-13. The highest IL-33 level was found in the atopic group, and the lowest in the control group. Participants currently exposed to farm animals were predisposed to have lower IL-33 serum level. Conclusion: Exposure of farm animals currently and in first year of life may result in a lower level of total IgE. Correlation between IL-13 and IL-33 serum levels and contact with livestock was not confirmed (AU)

Association of umbilical cord serum TARC/CCL17 with childhood allergies: A birth cohort study.

BACKGROUND: Early identification of infants at high risk of allergies can improve the efficacy of preventive interventions. However, an established quantifiable risk assessment method in the early postnatal period does not exist. TARC (or CCL17) is a Th2 chemokine used as an activity marker for atopic dermatitis (AD). Therefore, we evaluated the association between cord blood TARC (cTARC) and the development of allergic diseases in childhood. METHODS: This is a high-risk birth cohort for allergy, consisting of children with a family history of allergy. We collected 263 pairs of maternal and child cord blood samples perinatally and child blood samples at ages 1, 2, and 5 years. TARC and allergen-specific immunoglobulin E levels were measured, and the relationship between allergic diseases was analyzed. RESULTS: The median cTARC was 989 pg/mL (interquartile range [IQR]: 667-1430 pg/mL). The cTARC levels in children who developed AD were higher than those in children who did not develop AD, and the association strengthened with younger age (median [IQR] at 1 year: 1285 [816-1965] vs. 933 [662-1330] pg/mL, p < 0.01; at 2 years: 1114 [787-1753] vs. 950 [660-1373] pg/mL, p = 0.02). In the multivariate analysis, cTARC was associated with AD, egg white sensitization, food allergy, allergic rhinitis, and Japanese cedar pollen sensitization. CONCLUSIONS: cTARC was associated with the development of allergic diseases and allergen sensitization in early childhood. These results suggest that, infantile AD-mediated atopic march starts during fetal life, and this immune status is reflected in the cTARC at birth.

Tryptase in type I hypersensitivity.

Tryptase is currently the main mast cell biomarker available in medical practice. Tryptase determination is a quantitative test performed in serum or plasma for the diagnosis, stratification, and follow-up of mast cell-related conditions. The continuous secretion of monomeric α and ß protryptases forms the baseline tryptase level. Transient, activation-induced release of tryptase is known as acute tryptase. Because mast cells are tissue-resident cells, the detection of an acute tryptase release in the bloodstream is protracted, with a delay of 15 to 20 minutes after the onset of symptoms and a peak at approximately 1 hour. Constitutive release of tryptase is a marker of mast cell number and activity status, whereas transient release of mature tryptase is a marker of mast cell degranulation. Although consensual as a concept, the application of this statement in clinical practice has only been clarified since 2020. For baseline tryptase to be used as a biomarker, reference values need to be established. In contrast, defining a transient increase using acute tryptase can only be achieved as a function of the baseline status.

Detection of drug-specific immunoglobulin E (IgE) and acute mediator release for the diagnosis of immediate drug hypersensitivity reactions.

The diagnosis of a drug hypersensitivity reaction (DHR) is complex. The first step after taking the clinical history is to look for a sensitization to confirm or exclude the diagnosis and to identify the culprit drug. Skin tests are the primary means of detecting sensitization in DHR, but are associated with a risk for a severe reaction and may be contraindicated. In vitro tests offer the potential to support or confirm a diagnosis of DHR and influence medical decision making. For immediate-type DHR, a few validated assays for measurement of specific IgE (sIgE) are commercially available to a limited number of drugs. In addition, several home-made sIgE radioimmunoassays have been used in other studies. The sensitivity of the sIgE assay is drug-dependant and generally low (0-85%) for betalactams and reported heterogeneous for other drugs ranging from 26% for chlorhexidine and 44% for suxamethonium to 92% for chlorhexidine. However, as all these studies included patients, in whom DHR was confirmed only by skin tests and not by provocation, the results have to be interpreted carefully and may be unreliable. Determination of mediators during an acute phase of a reaction may indirectly support the diagnosis of a DHR by demonstrating mast cell and basophil mediator release. Negative in vitro tests do not exclude a DHR or imputability of a drug, but a positive result may support causality and eliminate the necessity for a drug provocation test. Unfortunately, evidence is limited with a lack of well-controlled studies in larger numbers of well-phenotyped patients, which results in susceptibility for bias and a need for future multicenter studies.

Serum-free immunoglobulin E: A useful biomarker of atopy and type 2 asthma in adults with asthma.

BACKGROUND: It has been known that a high serum total immunoglobulin E (IgE) level is a predisposing factor of allergic asthma; however, there are considerable limitations to apply it in clinical practice. OBJECTIVE: To determine the clinical significance of the serum-free IgE level in patients with adult asthma. METHODS: We measured free IgE levels using our homemade enzyme-linked immunosorbent assay by applying a novel IgE TRAP protein (GI innovation, Seoul, Republic of Korea) in sera of adults with asthma (n = 116) compared with healthy controls (n = 32); enzyme-linked immunosorbent assay inhibition test was performed to validate its binding specificity. Associations between asthma-related clinical and laboratory parameters were analyzed. The diagnostic value and cutoff point for detecting atopy and type 2 asthma were determined using receiver operating characteristic curve analysis. RESULTS: The serum-free IgE levels were significantly higher in adults with asthma than in healthy controls and were significantly associated with atopic status and type 2 asthma (all P < .001). In the receiver operating characteristic analysis, serum-free IgE had a significantly greater area under the curve (AUC) than serum total IgE for assessing asthma, especially type 2 asthma (AUC, 0.810 vs 0.743; P = .006 and AUC, 0.729 vs 0.572; P < .001). The optimal cutoff points for predicting atopy and type 2 asthma were 82.8 and 120.8 ng/mL, respectively. CONCLUSION: It is suggested that a higher serum-free IgE level may be a useful biomarker of atopy and type 2 asthma in adults with asthma.

Antibodies to Der p 1 and Der p 2 in allergic patients

Introduction and objectives Atopic individuals are characterized by increased IgE production and Th2 response if exposed to certain antigens. It is known that the mother transfers anti-mite antibodies to the fetus and newborn, IgG thru the placenta, and IgA thru breastfeeding, but it is not clear whether there is a protective mechanism mediated by them concerning the development of future allergies. This study aimed to compare the levels of IgA, IgG, and IgE antibodies specific to Der p 1 and Der p 2 between atopic and healthy individuals. Methods Serum samples of 98 patients and 44 healthy controls were subjected to quantification for specific IgE, IgG, and IgA antibodies against Der p 1 and Der p 2 by ImmunoCap® and ELISA, and subjected to statistical analysis as indicated. Results Atopic patients had higher serum levels of IgE, IgG, and IgA specific to Der p 1 and Der p 2. The correlation was more robust between IgE and IgG antibodies. Conclusions Allergic patients produce higher levels of antibodies against Der p 1 and Der p 2 compared with healthy individuals. The mechanisms involved still require detailed studies (AU)

Antibodies to Der p 1 and Der p 2 in allergic patients.

INTRODUCTION AND OBJECTIVES: Atopic individuals are characterized by increased IgE production and Th2 response if exposed to certain antigens. It is known that the mother transfers anti-mite antibodies to the fetus and newborn, IgG thru the placenta, and IgA thru breastfeeding, but it is not clear whether there is a protective mechanism mediated by them concerning the development of future allergies. This study aimed to compare the levels of IgA, IgG, and IgE antibodies specific to Der p 1 and Der p 2 between atopic and healthy individuals. METHODS: Serum samples of 98 patients and 44 healthy controls were subjected to quantification for specific IgE, IgG, and IgA antibodies against Der p 1 and Der p 2 by ImmunoCap® and ELISA, and subjected to statistical analysis as indicated. RESULTS: Atopic patients had higher serum levels of IgE, IgG, and IgA specific to Der p 1 and Der p 2. The correlation was more robust between IgE and IgG antibodies. CONCLUSIONS: Allergic patients produce higher levels of antibodies against Der p 1 and Der p 2 compared with healthy individuals. The mechanisms involved still require detailed studies.

Factors Influencing Total Serum IgE in Adults: The Role of Obesity and Related Metabolic Disorders.

BACKGROUND AND AIM: Few reports have investigated the association between metabolic abnormalities (obesity and related metabolic syndrome) and total serum IgE concentrations. METHODS: This cross-sectional study included a random sample of 1,516 adult individuals (44.7% men, aged 18-91 years, median 52 years) from a single municipality in Spain. Serum IgE was measured in the ADVIA Centaur system. Atopy was defined by the presence of positive skin prick tests to a panel of common aeroallergens in the area. Body mass index and data related to the definition of metabolic syndrome were obtained from all participants. Alcohol consumption, smoking, and regular physical exercise were assessed by a questionnaire. RESULTS: Atopy (present in 21.9% of 1,514 evaluable individuals) was the strongest factor determining serum IgE concentrations. Male sex and heavy alcohol drinking were independently associated with higher IgE concentrations, particularly in the non-atopic individuals. Body mass index was positively associated with IgE concentrations, independent of potential confounders, although the effect was only evident among non-atopic individuals. In that group, median IgE concentrations in normal-weight and obese individuals were 15 and 24 kU/L, respectively (p < 0.001); likewise, obesity was associated with high (>100 kU/L) IgE concentrations after adjusting for potential confounders (odds ratio: 1.79, 95% confidence interval: 1.26-2.56, p = 0.001). The presence of metabolic syndrome and its components, particularly abdominal obesity and hyperglycaemia, was also positively and independently associated with higher IgE concentrations in non-atopic individuals. CONCLUSIONS: Obesity and metabolic syndrome components are associated with high total serum IgE concentrations, particularly in non-atopic individuals.

Mast cell activation test in chlorhexidine allergy: a proof of concept.

BACKGROUND: Immediate drug hypersensitivity reactions are an increasing public health issue and a frequent cause of life-threatening anaphylaxis. Conventional confirmatory testing include skin tests and, for a few drugs, quantification of drug-specific immunoglobulin E (IgE) antibodies. However, none of these tests are absolutely predictive for the clinical outcome, and can yield false-negative and false-positive results. We performed a proof-of-concept study to assess whether a mast cell activation test could improve diagnosis of IgE-mediated chlorhexidine hypersensitivity, a common cause of perioperative anaphylaxis. METHODS: Human mast cells were generated from CD34+ progenitor cells and sensitised with patients' sera to become IgE+ human mast cells (dMCIgE+), and then incubated with chlorhexidine to assess degranulation. We compared the diagnostic performance of this mast cell activation test with serum from patients with and without positive skin test and basophil activation test to chlorhexidine. RESULTS: In dMC sensitised with sera from patients with a positive skin test and basophil activation test to chlorhexidine showed drug-specific and concentration-dependent degranulation upon stimulation with chlorhexidine, determined by surface upregulation of the degranulation marker CD63. In contrast, dMC sensitised with sera from patients with a negative skin test and basophil activation test to chlorhexidine were unresponsive in the mast cell activation test. CONCLUSIONS: Our study suggests that the mast cell activation test can be used to diagnose IgE/FcεRI-dependent immediate drug hypersensitivity reactions. It also shows potential to assess the clinical relevance of drug-specific IgE antibodies in their ability to elicit mast cell degranulation, and therefore discriminate between allergy and sensitisation. Extended studies are required to verify whether this technique can be used in other causes of perioperative anaphylaxis.

Expression Quantitative Trait Methylation Analysis Reveals Methylomic Associations With Gene Expression in Childhood Asthma.

BACKGROUND: Nasal (airway) epithelial methylation profiles have been associated with asthma, but the effects of such profiles on expression of distant cis-genes are largely unknown. RESEARCH QUESTION: To identify genes whose expression is associated with proximal and distal CpG probes (within 1 Mb), and to assess whether and how such genes are differentially expressed in atopic asthma. STUDY DESIGN AND METHODS: Genome-wide expression quantitative trait methylation (eQTM) analysis in nasal epithelium from Puerto Rican subjects (aged 9-20 years) with (n = 219) and without (n = 236) asthma. After the eQTM analysis, a Gene Ontology Enrichment analysis was conducted for the top 500 eQTM genes, and mediation analyses were performed to identify paths from DNA methylation to atopic asthma through gene expression. Asthma was defined as physician-diagnosed asthma and wheeze in the previous year, and atopy was defined as at least one positive IgE to allergens. Atopic asthma was defined as the presence of both atopy and asthma. RESULTS: We identified 16,867 significant methylation-gene expression pairs (false-discovery rate-adjusted P < .01) in nasal epithelium from study participants. Most eQTM methylation probes were distant (average distance, ∼378 kb) from their target genes, and also more likely to be located in enhancer regions of their target genes in lung tissue than control probes. The top 500 eQTM genes were enriched in pathways for immune processes and epithelial integrity and were more likely to have been previously identified as differentially expressed in atopic asthma. In a mediation analysis, we identified 5,934 paths through which methylation markers could affect atopic asthma through gene expression in nasal epithelium. INTERPRETATION: Previous epigenome-wide association studies of asthma have estimated the effects of DNA methylation markers on expression of nearby genes in airway epithelium. Our findings suggest that distant epigenetic regulation of gene expression in airway epithelium plays a role in atopic asthma.

Association of ABO blood groups with allergic diseases: a scoping review.

OBJECTIVE: The objective of this study was to map evidence of the association of ABO blood groups with allergic diseases such as allergic rhinitis (AR), atopic dermatitis (AD) and asthma. DESIGN: A scoping review. DATA SOURCES: PubMed, Scopus, Direct Open Access Journal, Medline, Cumulative Index to Nursing and Allied Health Literature, ScienceDirect and SpringerLink were searched from October 2017 until May 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We selected all types of studies including case-control studies, prospective or retrospective cohort studies, cross-sectional studies and experimental studies, and we included reviews such as literature reviews, systematic reviews with or without meta-analysis and scoping reviews that were published in English and associated the ABO blood group with the three allergic diseases (asthma, AR and AD) in humans of all age groups. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the titles and abstracts and assessed the full-text articles of the abstracts that met the eligibility requirements. Data from the included studies were extracted, evaluated and reported in the form of narrative synthesis. RESULTS: Of the 10 246 retrieved titles, only 14 articles were selected for a scoping review based on the eligibility criteria. The majority of the studies demonstrated a significant association between ABO blood groups and allergic diseases. We found that blood group O is prominent in patients with AR and asthma, while a non-O blood group is common in patients with AD. CONCLUSION: This scoping review serves as preliminary evidence for the association of ABO blood groups with allergic diseases. Further studies need to be conducted so that the relationship between ABO blood groups and allergic diseases can be fully established. This could be helpful for clinicians and health professionals in consulting and managing patients who suffer from allergic diseases in the future.

Biological Sex and IgE Sensitization Influence Severity of Depression and Cortisol Levels in Atopic Dermatitis.

BACKGROUND: Depression is a common comorbid condition with atopic dermatitis (AD), particularly during the active disease cycle. Controversial results regarding the contribution of biological sex, immunoglobulin E (IgE) sensitization, and cortisol on AD severity and comorbid depression justify further investigation. OBJECTIVE AND METHODS: To explore the influence of sex and IgE sensitization on biochemical and psychological parameters, and severity of AD, a case-control study of 105 volunteers (56 AD, 49 healthy controls (HC); 50 males, 55 females) was conducted over 10 weeks, starting at dermatological symptom onset. Disease severity, serum IgE, cortisol and testosterone levels, and depression scores were assessed at study baseline and after 10 weeks of conventional treatment. RESULTS: Dermatological severity differed among AD males by IgE sensitization and was elevated in males with extrinsic atopic dermatitis (EAD). Hamilton Depression Rating Scale (HAMD) scores were elevated in all patients at study baseline and improved with symptom reduction to HC levels, except female EAD. Severity of depression and dermatitis were correlated in EAD males at baseline and at week 10. Serum cortisol was elevated in male EAD at baseline, in contrast to males with intrinsic atopic dermatitis (IAD) at week 10. In addition, cortisol levels were found negatively correlated with SCORAD and HAMD scores in EAD males at week 10. CONCLUSION: Pathophysiological features of AD and depression are likely related to different inflammation-based effects and appear to be biological sex-dependent. Cortisol levels depend on biological sex and IgE sensitization in AD and increase in males with EAD at exacerbation and IAD males at resolution. Biological sex-related disease triggers, IgE sensitization, and cortisol levels are important for the understanding of the mechanisms underlying AD and comorbid depression.

Microfibrillar-associated protein 4 in serum is associated with asthma in Danish adolescents and young adults.

BACKGROUND: Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related protein superfamily, which plays multifaceted roles in innate immunity and normal endothelial function. It has been proposed that MFAP4 promotes the development of asthma in vivo and proasthmatic pathways of bronchial smooth muscle cells in vitro. The aim of this study was to investigate the significance of serum MFAP4 in adolescents and young adolescents with persistent asthma. METHODS: Prospective, observational study including adolescents and young adults (age 11-27 years) previously diagnosed with asthma during childhood 2003 to 2005 (0-15 years) at the four pediatric outpatient clinics in the Region of Southern Denmark (n = 449). Healthy controls were recruited at follow-up (n = 314). Detection of serum MFAP4 was performed by AlphaLISA technique. RESULTS: Current asthma was associated to a 14% higher mean level of serum MFAP4 compared with controls (expß 1.14, 95% confidence intervals [CI], 1.05-1.23) and a 6% higher mean level compared with subjects with no current asthma (expß 1.06, 95% CI, 0.99-1.13). No association was found at follow-up between serum MFAP4 and self-reported atopic symptoms (other than asthma), Asthma Control Test-score, fractional exhaled nitric oxide (FeNO), nor to flow rate at 1 second, forced vital capacity, and forced expiratory flow 25% to 75%, response to short-acting beta 2 agonist or mannitol. CONCLUSIONS: We found a significantly higher mean level of serum MFAP4 in adolescent and young adults with mild to moderate asthma compared with healthy controls but no association to FeNO and lung function nor to the response to short-acting beta 2 agonist or mannitol. The result supports the hypothesis that MFAP4 plays a role in the pathogenesis of asthma although the marker did not demonstrate any obvious potential as an asthma biomarker in adolescents and young adults with asthma. To understand the possible proasthmatic functions of MFAP4, further investigation in specific asthma phenotypes and the underlying molecular mechanisms is warranted.

Atopic Patients Show Increased Interleukin 4 Plasma Levels but the Degree of Elevation Is Not Sufficient to Upregulate Interleukin-4-Sensitive Genes.

BACKGROUND: Atopic diseases constitute a major health challenge for industrialized countries, and elevated levels of interleukin 4 (IL-4) frequently characterize these disorders. Previous in vitroanalyses have indicated that IL-4 strongly upregulates the expression of IL-4-sensitive genes in human monocytes. OBJECTIVE: To explore whether similar expression alterations may contribute to the pathomechanisms of atopic diseases in vivo we carried out a small-scale case-control clinical study (n = 43), in which we quantified the plasma levels of IgE and IL-4 as well as the expression of selected IL-4-sensitive genes in blood leukocytes. METHODS: 34 allergic patients suffering from allergic rhinitis (n = 11), atopic eczema (n = 11) and allergic asthma (n = 12) as well as 9 healthy control individuals were recruited. IgE and IL-4 plasma levels were determined by ELISA, and the expression of selected IL-4-sensitive gene products in blood leukocytes was quantified by qRT-PCR. In addition, the fatty acid oxygenase activity of isolated monocytes was measured by RP-HPLC analysis of the arachidonic acid oxygenation products (ex vivo activity assays). RESULTS: We found that plasma levels of IgE and IL-4 were significantly elevated in atopic patients but the degree of elevation was not sufficient to upregulate the expression of the selected IL-4-sensitive genes in circulating leukocytes. Moreover, the arachidonic acid oxygenase activity of blood monocytes was not significantly altered in atopic patients. CONCLUSION: Our data suggest that the IL-4 plasma levels of atopic patients are not high enough to impact the expression of IL-4-sensitive genes.

Immunological methods for diagnosis and monitoring of IgE-mediated allergy caused by industrial sensitizing agents (IMExAllergy).

Industrial sensitizing agents (allergens) in living and working environments play an important role in eliciting type 1 allergic disorders including asthma and allergic rhinitis. Successful management of allergic diseases necessitates identifying their specific causes (ie, identify the causative agent(s) and the route of contact to allergen: airborne, or skin contact) to avoid further exposure. Identification of sensitization by a sensitive and validated measurement of specific IgE is an important step in the diagnosis. However, only a limited number of environmental and occupational allergens are available on the market for use in sIgE testing. Accordingly, specific in-house testing by individual diagnostic and laboratory centers is often required. Currently, different immunological tests are in use at various diagnostic centers that often produce considerably divergent results, mostly due to lack of standardized allergen preparation and standardized procedures as well as inadequate quality control. Our review and meta-analysis exhibited satisfactory performance of sIgE detection test for most high molecular weight (HMW) allergens with a pooled sensitivity of 0.74 and specificity of 0.71. However, for low molecular weight (LMW) allergens, pooled sensitivity is generally lower (0.28) and specificity higher (0.89) than for HMW tests. Major recommendations based on the presented data include diagnostic use of sIgE to HMW allergens. A negative sIgE result for LMW agents does not exclude sensitization. In addition, the requirements for full transparency of the content of allergen preparations with details on standardization and quality control are underlined. Development of standard operating procedures for in-house sIgE assays, and clinical validation, centralized quality control and audits are emphasized. There is also a need for specialized laboratories to provide a custom service for the development of tests for the measurement of putative novel occupational allergens that are not commercially available.

Intralaboratory Reliability and Variability for Allergen-Specific Immunoglobulin Type E Serology Testing.

Atopic dermatitis is a very common condition affecting dogs and often managed with allergen-specific immunotherapy, which requires accurate identification of causative allergens. Serology testing is used commonly. Serum was collected from 35 atopic dogs and separated into three samples each (1, 2, and 3). Samples 1 and 2 were sent to IDEXX Laboratories the same day; sample 3 was stored at -80°C and submitted ∼30 days later. Specific immunoglobulin type E reactivity to various allergens were determined using monoclonal anti-canine enzyme-linked immunosorbent assay (ELISA) and expressed as ELISA absorbance units. Percent difference ranged from 14.30 to 127.34% for samples 1 and 2. These values increased when comparing samples a month apart (21.78 to 129.65%). Between samples 1 and 2, for each allergen there were differences in interpretation 15.18% of the time; 32 of 35 dogs (91.4%) had at least one allergen with a different interpretation. Comparing sample 3 and the average of samples 1 and 2, differences in interpretation increased to 22.32%; all dogs had at least one allergen that was interpreted differently. These differences in interpretation can alter immunotherapy. Overall, results show the need for better reliability for allergen-specific immunoglobulin type E serology testing using monoclonal anti-canine ELISA.

Crystal structure and epitope analysis of house dust mite allergen Der f 21.

Group 21 and 5 allergens are homologous house dust mite proteins known as mid-tier allergens. To reveal the biological function of group 21 allergens and to understand better the allergenicity of the rDer f 21 allergen, we determined the 1.5 Å crystal structure of rDer f 21 allergen from Dermatophagoides farinae. The rDer f 21 protein consists of a three helical bundle, similar to available structures of group 21 and homologous group 5 allergens. The rDer f 21 dimer forms a hydrophobic binding pocket similar to the one in the Der p 5 allergen, which indicates that both of the homologous groups could share a similar function. By performing structure-guided mutagenesis, we mutated all 38 surface-exposed polar residues of the rDer f 21 allergen and carried out immuno-dot blot assays using 24 atopic sera. Six residues, K10, K26, K42, E43, K46, and K48, which are located in the region between the N-terminus and the loop 1 of rDer f 21 were identified as the major IgE epitopes of rDer f 21. Epitope mapping of all potential IgE epitopes on the surface of the rDer f 21 crystal structure revealed heterogeneity in the sIgE recognition of the allergen epitopes in atopic individuals. The higher the allergen-sIgE level of an individual, the higher the number of epitope residues that are found in the allergen. The results illustrate the clear correlation between the number of specific major epitope residues in an allergen and the sIgE level of the atopic population.

Characteristics of inner-city children with life-threatening asthma.

BACKGROUND: Intensive care unit (ICU) admission is a risk factor for fatal asthma. Little is known about risk factors for pediatric ICU admissions for asthma. OBJECTIVE: To examine characteristics of underserved minority children with prior ICU admissions for asthma. METHODS: Baseline survey data, salivary cotinine levels, and allergen specific IgE serologic test results were obtained from children with uncontrolled asthma enrolled in a randomized clinical trial of a behavioral education environmental control intervention. Characteristics of children with and without prior ICU admission were compared using χ2 and t tests. Logistic regression assessed significance of higher odds of prior ICU admission comparing factor-level categories. RESULTS: Patients included 222 primarily African American (93.7%), male (56%), Medicaid-insured (92.8%) children with a mean (SD) age of 6.4 (2.7) years with uncontrolled asthma. Most (57.9%) had detectable cotinine levels, 82.6% were sensitized to more than 1 environmental allergen, and 27.9% had prior ICU admissions. Prior ICU patients were more likely to be very poor (<$10,000 per year) and sensitized to more than 1 allergen tested (most importantly mouse) (P < .05). Allergen sensitization in the groups did not differ for cockroach, cat, dog, Alternaria, Aspergillus, dust mite, grass, or tree. Although more ICU patients received combination controller therapy, they also overused albuterol. Only 27.4% of ICU patients received specialty care in the previous 2 years, which was not significantly different from non-ICU patients. CONCLUSION: Children with high mortality risk, including history of ICU admission, were twice as likely to live in extreme poverty, have atopy (particularly mouse allergen), use combination controller therapy, and overuse albuterol. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01981564.

Epigenetic age acceleration is associated with allergy and asthma in children in Project Viva.

BACKGROUND: Epigenetic clocks have been suggested to capture one feature of the complexity between aging and the epigenome. However, little is known about the epigenetic clock in childhood allergy and asthma. OBJECTIVE: We sought to examine associations of DNA methylation age (DNAmAge) and epigenetic age acceleration with childhood allergy and asthma. METHODS: We calculated DNAmAge and age acceleration at birth, early childhood, and midchildhood based on the IlluminaHumanMethylation450BeadChip in Project Viva. We evaluated epigenetic clock associations with allergy and asthma using covariate-adjusted linear and logistic regressions. We attempted to replicate our findings in the Genetics of Asthma in Costa Rica Study. RESULTS: At midchildhood (mean age, 7.8 years) in Project Viva, DNAmAge and age acceleration were cross-sectionally associated with greater total serum IgE levels and greater odds of atopic sensitization. Every 1-year increase in intrinsic epigenetic age acceleration was associated with a 1.22 (95% CI, 1.07-1.39), 1.17 (95% CI, 1.03-1.34), and 1.29 (95% CI, 1.12-1.49) greater odds of atopic sensitization and environmental and food allergen sensitization. DNAmAge and extrinsic epigenetic age acceleration were also cross-sectionally associated with current asthma at midchildhood. DNAmAge and age acceleration at birth and early childhood were not associated with midchildhood allergy or asthma. The midchildhood association between age acceleration and atopic sensitization were replicated in an independent data set. CONCLUSIONS: Because the epigenetic clock might reflect immune and developmental components of biological aging, our study suggests pathways through which molecular epigenetic mechanisms of immunity, development, and maturation can interact along the age axis and associate with childhood allergy and asthma by midchildhood.