Positive Allergen-specific IgE Research Articles

Long-Term PM2.5 Exposure and Upregulation of CLCA1 Expression in Nasal Epithelium from Youth with Asthma.

Little is known about long-term PM2.5 exposure and airway epithelial gene expression. To test for association between long-term PM2.5 exposure and nasal epithelial gene expression in youth with asthma. Transcriptome-wide association study (TWAS) of long-term PM2.5 in nasal epithelium from youth aged 6-20 years in the: 1) Epigenetic Variation and Childhood Asthma in Puerto Ricans study (EVA-PR, n=182); 2) Vitamin D Kids Asthma Study (VDKA, n=58); and 3) Stress and Treatment Response in Puerto Rican and African American Children with Asthma study (STAR, n=81). Satellite hybrid models were used to estimate PM2.5 exposure in the prior year at each participant's residence. Multivariable negative binomial regression was used for each TWAS, adjusting for age, sex, and other covariates. A meta-analysis of all TWAS results was then conducted using an inverse variance-weighted average approach. Most participants (~95%) in the meta-analysis of TWAS for PM2.5 exposure identified as Puerto Rican or Black. Long-term PM2.5 was associated with: 1) upregulated expression of CLCA1 (calcium-activated chloride channel regulator 1, false discovery rate-adjusted P [FDR-P]=0.008), SYCP2 (synaptonemal complex protein 2, FDR-P=0.01), and CYP2A6 (cytochrome p450 family 2 subfamily A member 6, FDR-P=0.02), and 2) downregulated expression of EDAR (ectodysplasin A receptor, FDR-P=0.01). In a meta-analysis, CLCA1 upregulation was associated with ≥1 positive allergen-specific IgE (FDR-P <0.001) and increased blood eosinophils (FDR-P <0.001) and total IgE (FDR-P <0.001). In a meta-analysis of TWASs in predominantly Puerto Rican and Black youth with asthma, long-term PM2.5 exposure was associated with upregulated airway epithelial CLCA1 expression, in turn linked to biomarkers of T2-high immunity.

Determination of the frequency of food allergen sensitivity in children with atopic dermatitis

Aims: We aimed to evaluate the frequency of food allergen sensitivity in children with atopic dermatitis (AD).&#x0D; Methods: The study is a descriptive study in a retrospective design. Children aged 0-18 years with AD were included in the study. The sociodemographic characteristics, laboratory parameters and the frequency of food allergen sensitivity were evaluated. Allergen sensitization was defined as a positive allergen-specific IgE or skin prick test.&#x0D; Results: The data of 295 patients with AD were evaluated. Food allergen sensitivity was detected in 34.2% (n=101) of them. Of the patients 21.4% (n=63) had a single food allergen sensitivity, whereas 12.9% (n=38) had multiple food allergen sensitivity. Egg was the most common food allergen (n=78, 26.4%). Patients with single food allergen sensitivity and multiple food allergen sensitivity were both significantly younger than those without food allergen sensitivity (p

Exposure to violence and asthma in Puerto Rican youth with high Th2 immunity.

Little is known about the determinants of asthma among youth with high T helper 2 (Th2) immunity. We hypothesized that exposure to violence (ETV) and violence-related distress are associated with asthma in children and adolescents with high Th2 immunity. We analyzed data from Puerto Ricans with high Th2 immunity aged 9-20 years in the Puerto Rico Genetics of Asthma and Lifestyle (PR-GOAL) and the Epigenetic Variation of Childhood Asthma in Puerto Ricans (EVA-PR) studies, and in a prospective study (PROPRA). High Th2-immunity was defined as ≥1 positive allergen-specific IgE and/or a total IgE ≥ 100 IU/mL and/or an eosinophil count ≥ 150 cells/μL. Asthma was defined as physician-diagnosed asthma and current wheeze. ETV and violence-related distress were assessed with the validated ETV Scale and Checklist of Children's Distress Symptoms (CCDS) questionnaires, respectively. In multivariable analyses, each 1-point increment in ETV score was significantly associated with 1.13-1.17 times increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.01), and each 1-point increment in CCDS score was significantly associated with 1.53-1.54 increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.03). Further, a persistently high ETV score was significantly associated with asthma in PROPRA (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.10-7.29). Similar results were obtained in a sensitivity analysis using an eosinophil count ≥ 300 cells/μL instead of ≥150 cells/μL to define high Th2 immunity. ETV during childhood is associated with increased risk of persistent or new-onset asthma in youth with high Th2 immunity.

IMPACT OF ALLERGEN SENSITIZATION ON AIRFLOW LIMITATION IN CHILDREN WITH SEVERE ASTHMA

<h3>Introduction</h3> Airflow limitation (AFL) has been shown to predict poor asthma outcomes across maturation. The objective of our study is to identify significant predictors of AFL in children with severe asthma from school-age to adolescence. <h3>Methods</h3> Children ages 5-18 years with treatment-refractory asthma underwent spirometry and diagnostic bronchoscopy. AFL was defined as pre-bronchodilator FEV₁/FVC <0.85 or <90% predicted. Demographics, treatments, and blood and lung markers of inflammation were analyzed with between group non-parametric tests and logistic regression models. <h3>Results</h3> 226 children were included in this analysis. Nearly one-half (n=105, 46%) had AFL. There was no difference in age, gender, BMI, or age of symptom onset between groups. Compared to children without AFL, those with AFL were more likely to have previous ICU admission for asthma, treatment with higher-dose inhaled corticosteroids (ICS), and reported black race. Children with AFL had significantly higher total blood and bronchoalveolar lavage (BAL) eosinophil count, total IgE, and greater number of positive allergen specific serum IgE. In younger children, those with sensitization to ≥4 allergens had greater airflow limitation but the opposite relationship was seen in adolescent children. Similarly, the effects of higher total IgE (>130 IU/mL) on airflow limitation were most prominent in younger children. <h3>Conclusion</h3> Significant predictors of airflow limitation in children with severe asthma include black race, previous ICU admission for asthma, higher-dose ICS treatment, and increased absolute blood and BAL eosinophil count. AFL is driven in part by allergic sensitization in the younger children whereas in older children this associated more with the absence of allergic sensitization.

Respiratory syncytial virus specific immunoglobulin G4 antibodies and atopic diseases in children.

It has been proposed that RSV infection stimulates RSV specific IgE and IgG4 production as a hallmark of Th2 immune response, which can contribute to the development of allergic sensitization and atopic diseases. This study intends to examine the occurrence of atopic diseases in children (wheezing bronchitis, food allergy, atopic dermatitis) and their connection with RSV specific IgE and IgG4 during the first two years of life. Prospective follow-up from the moment of birth was performed in 127 children with positive RSV specific IgG antibodies at age 1 and 92 children were followed-up until two years of age. The assessment included a structured interview, clinical examination, total blood eosinophils, serum total IgE and allergen specific IgE antibodies, RSV specific IgG, IgG3, IgG4 and IgE antibodies. Significant correlation was found between positive RSV IgG4 antibodies at year one and atopic dermatitis (Tau_b=0.201, P=0.025), as well as food allergy development (Tau_b=0.205, P=0.023). RSV specific IgG4 antibodies to RSV at year one showed significant prediction of increased total and/or allergen specific IgE (odds ratio 2.73 and 95% confidence interval 1.07 - 7.00, P=0.036). In our regression model, the children who had positive RSV IgG4 antibodies had a 2.73 times higher likelihood of having increased positive total and/or allergen specific IgE during the first two years of life. RSV specific IgG4 antibodies could be a marker of risk for the development of atopic sensitization to inhaled and food allergens, development of food allergy and atopic dermatitis in atopic children.

Serum allergen-specific IGE to common aeroallergens among allergic rhinitis patients in Egypt

BackgroundAllergic rhinitis is the most prevalent allergic disease, and the prevalence and sensitization patterns differ among countries. Identifying the most common inhalant allergen in each region plays a key role in the diagnosis and management of allergic rhinitis. There are no data available about the most prevalent aeroallergen among allergic rhinitis patients in Egypt. The aim of this study is to evaluate the prevalence of positive serum allergen-specific IGE to common inhalant allergens among allergic rhinitis patients in Egypt. A cross-sectional study was conducted on 354 allergic rhinitis patients, serum allergen-specific IGE was measured by using the Immuno CAP system to 16 common regional aeroallergens including (pollens, mite, molds, animal dander, and cockroach).ResultsThe overall rate of sensitization to any allergen was 74.6%. Dermatophagoides pteronyssinus, birch pollens, and Dermatophagoides farina were the most prevalent allergens (29.7%, 23.7%, and 18.6%), respectively. Cladosporuim molds were the least prevalent individual allergens (1.7%).ConclusionOur data suggest that Dermatophagoides pteronyssinus and birch pollens were the predominant allergen sources among allergic rhinitis patient in Egypt.

Outcomes of protracted bacterial bronchitis in children: A 5-year prospective cohort study.

Long-term data on children with PBB has been identified as a research priority. We describe the 5-year outcomes for children with PBB to ascertain the presence of chronic respiratory disease (bronchiectasis, recurrent PBB and asthma) and identify the risk factors for these. Prospective cohort study was undertaken at the Queensland Children's Hospital, Brisbane, Australia, of 166 children with PBB and 28 controls (undergoing bronchoscopy for symptoms other than chronic wet cough). Monitoring was by monthly contact via research staff. Clinical review, spirometry and CT chest were performed as clinically indicated. A total of 194 children were included in the analysis. Median duration of follow-up was 59 months (IQR: 50-71 months) post-index PBB episode, 67.5% had ongoing symptoms and 9.6% had bronchiectasis. Significant predictors of bronchiectasis were recurrent PBB in year 1 of follow-up (ORadj = 9.6, 95% CI: 1.8-50.1) and the presence of Haemophilus influenzae in the BAL (ORadj = 5.1, 95% CI: 1.4-19.1). Clinician-diagnosed asthma at final follow-up was present in 27.1% of children with PBB. A significant BDR (FEV1 improvement >12%) was obtained in 63.5% of the children who underwent reversibility testing. Positive allergen-specific IgE (ORadj = 14.8, 95% CI: 2.2-100.8) at baseline and bronchomalacia (ORadj = 5.9, 95% CI: 1.2-29.7) were significant predictors of asthma diagnosis. Spirometry parameters were in the normal range. As a significant proportion of children with PBB have ongoing symptoms at 5 years, and outcomes include bronchiectasis and asthma, they should be carefully followed up clinically. Defining biomarkers, endotypes and mechanistic studies elucidating the different outcomes are now required.

Relationship between gene polymorphism at rs2228055 locus in the exon region of interleukin-10 receptor A and susceptibility to food allergy in children

Objective: To investigate the relationship between gene polymorphism of rs2228055 locus in the exon region of interleukin-10 receptor A (IL-10RA) and susceptibility to food allergy in children. Methods: This was a case-control study. The food allergy group had 150 children who were diagnosed with food allergy in the Pediatric Food Allergy Clinic of Peking University Third Hospital from August 1, 2017 to November 30, 2018. Another 150 healthy children attended Child Health and Development Center in the same hospital were selected as control group. The genotypes of rs2228055 locus in both groups were detected by PCR re-sequencing. And the genotypes and allele frequencies of rs2228055 locus were compared between these two groups, as well as between food allergy children with positive and negative allergen specific IgE, and between those with and without involvement of different organs. Using the computer virtual mutation to stimulate the changes of amino acid caused by change of rs2228055 locus allele, to analyze the effect of amino acid changes on the structure of IL-10RA. The chi-square test was used for comparison between groups. Results: (1) There were 92 males and 58 females in food allergy group, and 86 males and 64 females in control group, without any statistically significant difference (χ(2)=0.497, P=0.481). The ages of the two groups were 4.2 (0.1-15.0) and 8.0 (0.1-14.0) years old, respectively, the difference was statistically significant (Z=-6.109, P<0.01). (2) The genotype frequencies of rs2228055 locus in the food allergy group and the control group were as follows: AA accounted for 73 (48.7%) and 98 (65.3%), AG accounted for 62 (41.3%) and 42 (28.0%), and GG accounted for 15 (10.0%) and 10 (6.7%), respectively. The allele frequencies in the two groups were as follows: 208 (69.3%) and 238 (79.3%) for A, 92 (30.7%) and 62 (20.7%) for G, respectively. AG and GG genotype frequency and the allele G frequency in food allergy group were significantly higher than that in control group (χ(2)=8.501 and 7.862, P=0.014 and 0.005, respectively). (3) There were no significant differences in genotype frequencies and allele frequencies of rs2228055 locus of allergen-specific IgE-positive and negative food allergy children (all P>0.05). (4) There were no significant differences in genotype frequencies and allele frequencies of rs2228055 locus in the manifestations of skin, digestive system and respiratory system in food allergy children (all P>0.05). (5) The computer virtual mutation showed that the mutation energy was -0.08 without any increase in the stability of IL-10RA when the amino acid encoded by rs2228055 locus was changed from isoleucine to valine. Conclusions: The frequencies of genotype AG, GG and allele G of rs2228055 locus in the IL-10RA exon region in food allergy children are higher than that in non-allergic children, and those with the G allele are more likely to develop food allergy.

Serum allergen-specific IgE reactivity: is there an association with clinical severity and airway eosinophilia in asthmatic cats?

The aim of this study was to evaluate the results of serum allergen-specific IgE testing in cats with a clinical diagnosis of asthma and to determine if the number of allergens with positive IgE reactivity and magnitude of positive IgE responses would be associated with the severity of clinical signs or airway eosinophilia. Medical records from 2008 to 2018 were retrospectively reviewed. Inclusion required a diagnosis of feline asthma based on consistent clinicopathologic features and bronchoalveolar lavage (BAL) cytology with >10% eosinophils; additionally, cats needed to have the results of serum allergen-specific IgE tests. Eighteen cases satisfied the inclusion criteria. Median age was 5 years and the most common presenting clinical sign was cough (n = 10/18). Most cats lived exclusively indoors (n = 13/18). The median percentage of BAL eosinophils was 47%. Serum allergen-specific IgE testing supported an underlying allergic etiology in 14/18 (78%) cats, with all but one having polysensitization. The severity of clinical signs and magnitude of airway eosinophilia did not correlate with the degree of positive IgE reactivity. This study identified a strong association between the identification of allergen-specific IgE and cats with asthma, and the majority of these cats were polysensitized. However, larger numbers of allergens with positive IgE reactivity or magnitude of IgE reactivity were not significantly associated with clinical severity or airway eosinophilia. Knowledge of positive allergen-specific IgE results could guide allergen avoidance, regardless of the magnitude of IgE reactivity.

Trends in aeroallergen sensitization in Germany – An analysis of 2919 serological data sets of a university ENT department

Background: Recently, population-based birth-cohort studies provided an insight into the allergic march during childhood.Aims: Our study aimed to investigate sensitization pattern until advanced age.Patients and methods: Demographic, clinical and serological characteristics of 2919 patients with positive allergen-specific IgE between 1999 and 2019 were analyzed. We performed subgroup analysis of various age-groups and different years of birth to distinguish between age-dependent changes and birth-cohort-effects.Results: Since 1999, the proportion of sensitized children has significantly increased. The prevalence of sIgE towards most allergens reached its peak in adolescence or young adulthood. Only to mites, the highest rate of sensitization was found in childhood. With further aging, the prevalence of sIgE significantly decreased in most sensitizations. Only to Fagales, the highest rate of sensitization was observed among patients >65 years. The year-of-birth analysis proved the above-mentioned changes to be age-dependent. Further, it revealed various sensitization trends from older to younger generations.Conclusions and significance: The increased proportion of children with sensitization during the last 20 years outlines the allergy epidemic. Probably due to immunosenescence, the aeroallergen sensitization rates decreased with aging, except for Fagales. Over time, different aeroallergens gained or lost relevance, potentially due to environmental and life-style changes.

The Natural Course of Immediate-Type Cow’s Milk and Egg Allergies in Children

Background: Most of children with cow’s milk (CM) and hen’s egg allergies are known to outgrow their diseases with time, but recent studies have demonstrated that children tend to continue to have allergic symptoms in adolescence and adulthood. The aim of this study was to investigate the natural course of CM and egg allergies in Korean children and analyze prognostic factors. Methods: In this retrospective study, we reviewed data of children with CM allergy and with egg allergy using medical records and parental telephone interviews. Diagnosis of CM or egg allergy was based on positive oral food challenge test or convincing history of allergic symptoms in combination with positive allergen-specific IgE. Acquisition of tolerance was defined by the absence of allergic symptoms after reintroduction of the offending foods. Results: Half of the children outgrew CM allergy at a median age of 8.7 years. CM-specific IgE level at the first reaction was a significant prognostic factor for oral tolerance in CM allergy (p < 0.05). The median age to acquire oral tolerance in 50% of patients with egg allergy was 5.6 years. Egg-specific IgE level at the first reaction and family history of allergic diseases significantly affected the prognosis in children with egg allergy (p < 0.05). Conclusions: Half of Korean children with CM and egg allergies had symptom resolution at 8.7 and 5.6 years of age, respectively. Our results also suggest that CM- and egg-specific IgE levels at the first reaction are the most significant prognostic factors in predicting acquisition of oral tolerance.

Association of allergic rhinitis, coronary heart disease, cerebrovascular disease, and all-cause mortality

BackgroundInflammation is implicated in atherosclerotic cardiovascular disease. Allergic diseases also involve a systemic inflammatory state, which may potentiate cardiovascular disease. ObjectiveTo examine the association of allergic rhinitis, coronary heart disease (CHD), cerebrovascular disease (CVD), and all-cause mortality. MethodsWe conducted a retrospective, population-based, matched cohort study comparing the incidence of CHD, CVD, and all-cause mortality from January 1, 1999, through December 31, 2012, in patients with International Classification of Disease, Ninth Revision, documented allergic rhinitis matched 1:1 by age, sex, and ethnicity to a reference cohort without allergic rhinitis within Kaiser Permanente Southern California. Fully adjusted hazard ratios (HRs) were calculated. Further analyses for those with positive environmental allergen specific IgE (sIgE) test results within the allergic rhinitis cohort were also performed. ResultsPatients with physician-diagnosed allergic rhinitis (N = 110, 207 in matched cohort) had significantly lower risk for myocardial infarction (HR, 0.63; 95% confidence interval [CI], 0.59–0.67; P < .001), all CHD (HR, 0.81; 95% CI, 0.78–0.84; P < .001), CVD (HR, 0.67; 95% CI, 0.64–0.70; P < .001), and all-cause mortality (HR, 0.42; 95% CI, 0.40–0.43; P < .001). The results were similar after excluding patients with asthma. Patients with positive sIgE test result also had a decreased risk of all CHD (relative risk [RR], 0.87; 95% CI, 0.79–0.95; P = .003) but no association with cerebrovascular events (RR, 0.89; 95% CI, 0.77–1.02; P = .10) and all-cause mortality (RR, 1.16; 95% CI, 1.00–1.34; P = .06). ConclusionWe found that the presence of allergic rhinitis was associated with decreased CHD, CVD, and all-cause mortality. This decreased risk was more pronounced after excluding patients with asthma. Patients with positive sIgE test results also had decreased risk of CHD.

Prevalence of Inhalant Allergic Rhinitis in Children with Adenoid Hypertrophy: A Prospective Radioallergosorbent Test (Rast) Study

Introduction:Children with allergic rhinitis are susceptible to adenoidal hypertrophy when compared to children with no allergies. We conducted this study to determine the prevalence of inhalant allergic rhinitis among children aged 2 to 10 years admitted for adenoidectomy by performing radioallergosorbent test (RAST). Material and Methods:75 children who underwent adenoidectomy at Hamad Medical Corporation, Doha, Qatar were recruited prospectively. 41 (54.7%) were males and 34 (45.3%) were females with a mean age of 4.9±4.5 years. Blood samples were collected for total IgE and allergen specific IgE antibodies during preoperative assessment or during intravenous induction for general anesthesia. Results:34 (45.3%) out of 75 children had increased total IgE, 19 (25.3%) had positive allergen specific IgE antibodies and 7 (9.3%) had both positive. Snoring 73 (97.3%) was the most common symptom, followed by mouth breathing 72 (96%), nasal blockage 61 (81.5%), rhinorrhea 34 (45.3%) and sneezing 11 (14.7%). Association of nasal symptoms with total IgE and allergen specific IgE antibodies showed no statistical significance. Association of asthma 29 (38.7%), eczema 10 (13.3%) and family history 31 (41.3%) were also not statistically significant. Conclusion:The result of our study suggests high prevalence of allergy sensitization among children who underwent adenoidectomy but poorly correlated with nasal symptoms. However, snoring and mouth breathing were found to be statistically significant (p=0.01) and specific for adenoid hypertrophy in patients without allergic rhinitis. In addition, nasal blockage is more specific (p=0.02) for with normal total serum IgE levels.

Clinical Features of Adult/Adolescent Atopic Dermatitis and Chinese Criteria for Atopic Dermatitis.

Background:Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD.Methods:A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software.Results:A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients.Conclusion:Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.

Obesity and rhinitis in a nationwide study of children and adults in the United States

Obesity has been associated with higher risk of asthma and asthma severity both in children and adults. However, studies evaluating the relation between obesity and rhinitis have yielded conflicting results. We performed a cross-sectional study of obesity indicators and rhinitis using data from 8165 participants in the 2005-2006 National Health and Nutrition Examination Survey. Allergic rhinitis was defined as physician-diagnosed hay fever or allergy, the presence of symptoms in the past 12months, and at least 1 positive allergen-specific IgE level. Nonallergic rhinitis was defined as a physician's diagnosis and symptoms but no positive allergen-specific IgE levels. Multivariate regression was used to assess the relationship between obesity and rhinitis in children and adults. In adults, overweight or obesity was associated with increased odds of nonallergic rhinitis (adjusted odds ratio, 1.43; 95% CI, 1.06-1.93; P=.02). Similarly, central obesity was associated with increased odds of nonallergic rhinitis in adults (adjusted odds ratio, 1.61; 95% CI, 1.20-2.16; P<.01). In an analysis stratified by sex, the observed associations were attenuated and became nonstatistically significant in female adults but remained significant in male adults. Overweight, obesity, or central obesity were not associated with allergic rhinitis in adults. In children, central obesity was associated with reduced odds of allergic rhinitis (adjusted odds ratio, 0.35; 95% CI, 0.19-0.64; P<.01). After stratification by sex, this association was similar in female and male children. In adults, obesity is associated with increased odds of nonallergic rhinitis, particularly in male subjects. In children, central obesity is associated with reduced odds of allergic rhinitis, regardless of sex.

Clinical laboratories worldwide need to report IgE antibody results on clinical specimens as analytical results and not use differential positive thresholds

Clinical laboratories worldwide need to report IgE antibody results on clinical specimens as analytical results and not use differential positive thresholds

Allergen Specific IgE Response Is Similar in HIV-1 Seropositive and Seronegative Adults: Implications for HAART Induced Th2 to Th1 Switching

FEBRUARY 2015 AB8 Abstracts S A T U R D A Y 24 Allergen Specific IgE Response Is Similar in HIV-1 Seropositive and Seronegative Adults: Implications for HAART Induced Th2 to Th1 Switching Mili Shum, MD, Ashlei Mathew, MD, Maja Nowakowski, PhD, Hamid Moallem, MD, Tamar A. Smith-Norowitz, PhD, Helen G. Durkin, PhD, Rauno O. Joks, MD, FAAAAI; State University of New York Downstate Medical Center, Brooklyn, NY, Center for Allergy and Asthma Research, State University of New York Downstate Medical Center, Brooklyn, NY, Center for Allergy and Asthma Research at SUNY Downstate Medical Center, Brooklyn, NY, SUNY Downstate Medical Center, Brooklyn, NY, Center for Allergy and Asthma Research, SUNY Downstate, Brooklyn, NY. RATIONALE: Advanced HIV disease has been associated with Th2 mediated IgE responses, including IgE anti-HIV, and decreased atopy. The effect of HAART (highly active antiretroviral therapy) on Th2 mediated allergic IgE responses has not been determined. METHODS: Retrospective chart review was performed for adults seen in Allergy clinic at University Hospital of Brooklyn during 7/2000 to 5/2014. Subjects included HIV-1 patients on HAART and a control group consisting of HIV-1 seronegative patients (age and sex matched with a clinical visit in the samemonth). Total and allergen specific serum IgE was determined by ImmunoCAP assay; Skin prick test (SPT, Dermapik) for aeroallergens was performed using the Dermapik method. A mixed linear model was constructed for each dependent variable (IgE, no. of positive allergy results). Fixed factors were HIV status and gender; age was introduced as a linear covariate; matched pair ID was introduced as a random factor. RESULTS: Seventy-four subjects were analyzed with equal number of subjects in each group. HIV-1 seropositive subjects on HAART and controls had similar total serum IgE of 90.95 IU/ml and 144.54 IU/ml respectively (p50.23) and similar numbers of positive allergen specific IgE responses of 3.34 and 4.06, respectively (p50.28). CONCLUSIONS: These findings suggest there is limited effect of HAART on Th2 to Th1 switching.

Component-resolved diagnosis using microarray for diagnosing hypersensitivity to raw fruits in birch pollen sensitized children

Purpose: Recently, component-resolved diagnosis (CRD) using microarray technology has been introduced to the field of clinical allergy. This study was aimed to investigate the clinical usefulness of microarray-based IgE detection for diagnosing clinical raw fruit allergy in birch pollen-sensitized children. Methods: Thirty-one children with allergic disease who had been sensitized to pollen were studied. A pollen-sensitized patient was defined as having an allergen-specific history with concomitant positive skin-prick tests (SPTs) to natural allergen extracts or positive allergen-specific IgE. All subjects underwent SPTs for pollen and fruit. In all subjects, specific IgE to pollen and fruit were measured by ImmunoCAP. Specific IgE antibodies to allergen components were determined by a customized allergen microarray (ISAC). Results: Thirteen of the 31 patients (41.9%) had a history of fruit hypersensitivity with positive SPTs. Measuring IgE to allergen components by ISAC, all the 13 patients with fruit hypersensitivity were positive to at least one of Mal d 1, Pru p 1, Pru p 3, Act d 8, and Act d 2 compared to 12 of the 13 patients (92.3%) who had at least 1 positive IgE to fruits (apple, peach, and kiwi) using ImmunoCAP. The sensitivity of ISAC microarray was 100.0% for the diagnosis of fruit hypersensitivity, but its specificity was 27.7% (5/18). The sensitivity of ImmunoCAP was 92.3%, and its specificity was 83.3%. Conclusion: The sensitivity of allergen components tested using microarray for the diagnosis of clinical fruit hypersensitivity in children with pollen allergy was high; however, its specificity was low.(Allergy Asthma Respir Dis 2015;3:200-205)

Response to letter regarding article ‘Exploring the link between pholcodine exposure and neuromuscular blocking agent anaphylaxis’

Uyttebroek et al. [1] raise some pertinent questions regarding the utility of various testing modalities in the assessment of neuromuscular blocking agent (NMBA) hypersensitivity. In our cases, clinical history was the major assessment tool for identifying pholcodine as the inciting agent of anaphylaxis [2]. In both patients, the temporal association between pholcodine exposure and clinical reaction was in keeping with drug-induced anaphylaxis and no alternative causes were identified. The positive allergen-specific IgE levels to pholcodine (ImmunoCAP Phadia, Uppsala, Sweden) were used to substantiate the high index of clinical suspicion. As mentioned in the article, skin testing to pholcodine has limited utility because it causes wheal and flare reactions in normal control subjects. While drug provocation challenges are sometimes used to confirm allergy in situations where history and skin/allergen-specific IgE testing are ambiguous, in this circumstance this was not felt appropriate, owing to the severity of systemic reaction in both patients' index events. In one of our cases, a tramadol challenge was performed to give additional options if opiate analgesics were required, and the avoidance of codeine and its active metabolite morphine was recommended. Subsequent evaluation in both our patients was targeted toward the potential for NMBA hypersensitivity given previous studies [3–6], presented in the review, suggesting an association between pholcodine exposure and NMBA anaphylaxis. The recommendations regarding NMBA use in both patients were based on the outcome of skin testing and allergen-specific IgE testing. As Uyttebroek et al. [1] allude to, sensitization to a drug does not always equate with clinically meaningful allergy. However, provocation challenges with various NMBAs, as a means of demonstrating patient tolerance or allergy, are not feasible. Thus, the recommendations were made on the available testing at the time of assessment. The development of basophil activation tests as an adjunct to skin testing and specific IgE testing will no doubt help in the assessment of cases of suspected drug allergy. However, these tests are currently not validated or routinely available in most centres, and sensitivity may be lacking even when cases are carefully phenotyped and selected. The cases presented demonstrate the potential for sensitization to NMBA to occur in the context of pholcodine hypersensitivity. These case studies are reflective, at an individual patient level, of the population-based evidence cited previously [3,5,6]. We agree that consideration of whether the patients are able to tolerate opiates following true pholcodine immediate (IgE) hypersensitivity reactions is an important practical concern, and the specific haptenated products mediating such reactions are unknown. Indeed, codeine is metabolized by the genetically polymorphic isoform CYP2D6 to the active metabolite morphine, adding additional potential variability to potential cross-reactivity and patient tolerance. However, the focus of our article [2] was on the potential association of pholcodine exposure and NMBA allergy, and thus, the presentation of the case studies reflects this. Immunoglobulin E-mediated hypersensitivity reactions to pholcodine and morphine are rare, and this does indeed raise important questions regarding the pathogenesis of pholcodine sensitization and NMBA anaphylaxis. At present, the mechanisms underlying why exposure and sensitization to a substituted ammonium ion in pholcodine can prime NMBA anaphylaxis but not result in allergy to all compounds containing similar substituted ammonium ions remain unresolved.

Allergen-specific IgE Antibody Serologic Assays in Patients with Autoimmune Pancreatitis

To clarify the allergic manifestations in patients with autoimmune pancreatitis (AIP). We assessed 67 AIP patients, before they received steroid therapy, for a past history of allergic disease, the peripheral eosinophil count (n=62) and the serum IgE level (n=53). Allergen-specific IgE antibody serologic assays were performed in 15 patients. A positive past history and/or the presence of active allergic disease were found in 24 AIP patients (36%), including 15 patients with acute allergic rhinitis and eight patients with bronchial asthma. Peripheral eosinophilia and elevation of the serum IgE level were detected in 16% (10/62) and 60% (32/53) of the patients, respectively. Allergen-specific IgE antibody serologic assays were positive in 13 patients (87%). There were no differences between the assay-positive and -negative patients regarding the clinical profiles. In conclusion, 87% of the 15 AIP patients tested had positive allergen-specific IgE antibody serologic assays. Allergic mechanisms may be related to the occurrence of AIP.