Lisa J. Workman

Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children.

BACKGROUND Maternal diet during pregnancy may affect childhood allergy and asthma. OBJECTIVE We sought to examine the associations between maternal intake of common childhood food allergens during early pregnancy and childhood allergy and asthma. METHODS We studied 1277 mother-child pairs from a US prebirth cohort unselected for any disease. Using food frequency questionnaires administered during the first and second trimesters, we assessed maternal intake of common childhood food allergens during pregnancy. In mid-childhood (mean age, 7.9 years), we assessed food allergy, asthma, allergic rhinitis, and atopic dermatitis by questionnaire and serum-specific IgE levels. We examined the associations between maternal diet during pregnancy and childhood allergy and asthma. We also examined the cross-sectional associations between specific food allergies, asthma, and atopic conditions in mid-childhood. RESULTS Food allergy was common (5.6%) in mid-childhood, as was sensitization to at least 1 food allergen (28.0%). Higher maternal peanut intake (each additional z score) during the first trimester was associated with 47% reduced odds of peanut allergic reaction (odds ratio [OR], 0.53; 95% CI, 0.30-0.94). Higher milk intake during the first trimester was associated with reduced asthma (OR, 0.83; 95% CI, 0.69-0.99) and allergic rhinitis (OR, 0.85; 95% CI, 0.74-0.97). Higher maternal wheat intake during the second trimester was associated with reduced atopic dermatitis (OR, 0.64; 95% CI, 0.46-0.90). Peanut, wheat, and soy allergy were each cross-sectionally associated with increased childhood asthma, atopic dermatitis, and allergic rhinitis (ORs, 3.6 to 8.1). CONCLUSION Higher maternal intake of peanut, milk, and wheat during early pregnancy was associated with reduced odds of mid-childhood allergy and asthma.

Anti-galactose-α-1,3-galactose IgE from allergic patients does not bind α-galactosylated glycans on intact therapeutic antibody Fc domains

Anti-galactose-α-1,3-galactose IgE from allergic patients does not bind α-galactosylated glycans on intact therapeutic antibody Fc domains

Galactose-α-1,3-galactose and Delayed Anaphylaxis, Angioedema, and Urticaria in Children

BACKGROUND AND OBJECTIVE: Despite a thorough history and comprehensive testing, many children who present with recurrent symptoms consistent with allergic reactions elude diagnosis. Recent research has identified a novel cause for “idiopathic” allergic reactions; immunoglobulin E (IgE) antibody specific for the carbohydrate galactose-α-1,3-galactose (α-Gal) has been associated with delayed urticaria and anaphylaxis that occurs 3 to 6 hours after eating beef, pork, or lamb. We sought to determine whether IgE antibody to α-Gal was present in sera of pediatric patients who reported idiopathic anaphylaxis or urticaria. METHODS: Patients aged 4 to 17 were enrolled in an institutional review board–approved protocol at the University of Virginia and private practice allergy offices in Lynchburg, VA. Sera was obtained and analyzed by ImmunoCAP for total IgE and specific IgE to α-Gal, beef, pork, cat epithelium and dander, Fel d 1, dog dander, and milk. RESULTS: Forty-five pediatric patients were identified who had both clinical histories supporting delayed anaphylaxis or urticaria to mammalian meat and IgE antibody specific for α-Gal. In addition, most of these cases had a history of tick bites within the past year, which itched and persisted. CONCLUSIONS: A novel form of anaphylaxis and urticaria that occurs 3 to 6 hours after eating mammalian meat is not uncommon among children in our area. Identification of these cases may not be straightforward and diagnosis is best confirmed by specific testing, which should certainly be considered for children living in the area where the Lone Star tick is common.

Regulation of Gonadotropin Subunit Gene Transcription by Gonadotropin-Releasing Hormone: Measurement of Primary Transcript Ribonucleic Acids by Quantitative Reverse Transcription-Polymerase Chain Reaction Assays1

GnRH regulates the synthesis and secretion of the pituitary gonadotropins LH and FSH. One of the actions of GnRH on the gonadotropin subunit genes (α, LHβ, and FSHβ) is the regulation of transcription [messenger RNA (mRNA) synthesis]. Gonadotropin subunit transcription rates increase after gonadectomy and following exogenous GnRH pulses. However, prior studies of subunit mRNA synthesis were limited by the available methodology that did not allow simultaneous measurement of gene transcription and mature mRNA concentrations. The purpose of the current studies was to: 1) develop a reliable and sensitive method for assessing transcription rates by measuring gonadotropin subunit primary transcript RNAs (PT, RNA before intron splicing); 2) investigate the PT responses to GnRH following castration or exogenous GnRH pulses; 3) characterize the half-disappearance time for the three PT species after GnRH withdrawal; and 4) correlate changes in PT concentration with steady-state gonadotropin subunit mRNA levels meas...

Peanut allergy prevalence among school-age children in a US cohort not selected for any disease

To the Editor: What is the prevalence of peanut allergy among US children? Given that 90% of US households consume peanut butter,1 this is an important question. The answer is not straightforward, however, as estimates of peanut allergy prevalence among US children differ by allergy definition, study population, and methodology.2 Previous estimates for US children have been based on self-report3–6 or specific IgE (sIgE) criteria,7 which are thought to be inaccurate.2 Estimates have varied according to whether they were based on telephone surveys,3 electronic surveys,4 or nationally representative surveys such as the National Health and Nutrition Examination Survey (NHANES) (Table 1).5–7 One must consider that self-report is hindered by reporting bias, surveys of food allergy are more likely to enlist those with the condition, and nationally representative surveys are limited in the extent of phenotyping possible given their wide scope. It can therefore be difficult to discern how differences in definition, study population, and methodology affect prevalence estimates across studies. Here we report and compare prevalence estimates of childhood peanut allergy according to varying criteria among 7–10 year-old children participating in a US birth cohort not selected for any disease. Table 1 Previously reported prevalence estimates of childhood peanut allergy in the US We determined prevalence of childhood peanut allergy based on reported symptoms, sIgE levels, clinical information, and combinations of these variables among participants of Project Viva. Project Viva is a large, observational cohort study based in eastern Massachusetts with enrollment from Harvard Vanguard Medical Associates, a multi-site group medical practice. Participants were not selected for any disease. The study was designed to examine maternal dietary and other factors that could influence child health outcomes, with health broadly defined.8 Enrollment occurred between 1999 and 2002 in early pregnancy and resulted in delivery of 2128 singleton children. Interviews and questionnaires on child health were administered when the children were age 6 months, 1 year, and annually thereafter. We collected outcome data for this study at the mid-childhood in-person visit (mean age 7.9 years). Among the 1277 children who presented for an in-person interview at mid-childhood, 699 (55%) had blood drawn, and 616 (87.7% of those with blood samples) had sIgE measured by Phadia ImmunoCAP. Compared to those who did not follow up, participants who did follow up showed higher proportions of maternal white race (69% vs. 62%), college or graduate education (69% vs. 58%), and annual household income (63% vs. 58%), but there were no significant differences in parental atopy (P value 0.13). Compared with the general US population, there was a higher proportion of blacks and lower proportion of Hispanics among participants. Further details regarding the comparability of the 616 children to the larger cohort have been previously described.8 We considered a child to have self-reported peanut allergy if his/her mother answered yes to, “Has your child ever had an allergic reaction to peanuts,” and yes to at least one of the following categories of allergic reaction symptoms with peanut ingestion: “Skin related (e.g. hives, swelling),” “Respiratory (e.g., shortness of breath, wheezing, cough),” “Cardiovascular (e.g. low blood pressure, dizziness or fainting,” “Gastrointestinal (e.g. vomiting, diarrhea),” or “Anaphylaxis (severe, multi-system allergic reaction).” These questions, which assess convincing symptoms of IgE-mediated reaction, are comparable to those used in previous studies of self-reported peanut allergy by Sicherer et al.3 We assessed prescription of an epinephrine auto-injector with the question, “Has a health care professional, such as a doctor, physician assistant or nurse practitioner, ever prescribed an EpiPen for your child?” The prevalence of self-reported peanut allergy in this cohort of US children not selected for any disease was 4.6% (Table 2), higher than previously reported estimates of self-reported peanut allergy among US children of comparable age (Table 1). Similarly, we observed a 5.0% prevalence of “clinical peanut allergy” according to sIgE-based criteria that previously resulted in a 2.7% prevalence among comparably aged children in the 2005–2006 NHANES study.7 Within Project Viva, the 4.9% prevalence of peanut allergy defined by both sensitization and prescribed epinephrine auto-injector was similar in magnitude to the estimates defined by self-reported allergy and sIgE-based “clinical allergy” criteria. Table 2 Prevalence of peanut allergy among school-age children in a US observational birth cohort not selected for any disease (N = 616) The relatively high prevalence rates we observed may reflect continued rise of peanut allergy prevalence in the US, consistent with the rising trend in self-reported peanut allergy that Sicherer et al. observed between 1997, 2002, and 2008.3 Additionally, our cohort was based in the Northeast, where rates of peanut sensitization may be higher relative to western US regions.9 Application of a more stringent definition for peanut allergy than self-reported allergy or “clinical allergy,” such as the peanut sIgE ≥ 14 kU/L decision point for 90% specificity reported by Sampson,10 yielded a prevalence of 2.9% (Table 2), which is still higher than previously reported estimates by any criteria (Table 1). Our strictest definition of peanut allergy, requiring peanut sIgE greater than the 90% specificity decision point and prescribed epinephrine auto-injector, yielded a prevalence of 2.0%. While it could be argued that despite Project Viva’s general health goals, the relatively high prevalence rates we observed could be due to food allergic families preferentially returning for mid-childhood visits, the rates of parental atopy (assessed prenatally) among those who did and did not present at mid-childhood were not significantly different, supporting that selection bias was not at play. As we assessed peanut allergy using different criteria within this cohort, we also assessed for agreement between the definitions. Agreement was the highest between self-reported peanut allergy and peanut allergy defined by both peanut sensitization and prescribed epinephrine auto-injector (Κ = 0.75, 95%CI 0.62–0.88). There was moderate agreement between self-reported peanut allergy and peanut allergy defined by both the 90% specificity decision point and prescribed epinephrine auto-injector (Κ = 0.57, 95%CI 0.38–0.76), and less agreement between self-reported peanut allergy and peanut allergy defined by the 90% specificity decision point only (Κ = 0.49, 95%CI 0.31–0.68). Each epidemiologic method for assessing peanut allergy prevalence has strengths and limitations. Double-blind, placebo-controlled food challenges are the gold standard for clinical peanut allergy diagnosis, but these are challenging to implement in large, unselected cohorts and have not been done in unselected US cohorts.2 As diagnostic adjuncts, component resolved diagnostics may also be increasingly implemented in epidemiologic cohorts going forward. In this letter, we have provided prevalence estimates according to several criteria that can be compared to one another and to previous estimates. Our results come from a US cohort of children not selected for allergy or any disease, and they support that peanut allergy is an increasingly prevalent condition.

Sensitization to food and inhalant allergens in relation to age and wheeze among children with atopic dermatitis.

Atopic dermatitis (AD) is common in children; however, persistence of AD with or without asthma is less common. Longitudinal studies remain limited in their ability to characterize how IgE antibody responses evolve in AD, and their relationship with asthma.

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

Most 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.

Gonadotropin Subunit Transcriptional Responses to Calcium Signals in the Rat: Evidence for Regulation by Pulse Frequency

Abstract Alterations in the frequency of calcium influx signals to rat pituitary cells can regulate the expression of gonadotropin subunit mRNAs in a differential manner, producing effects that are similar to those previously found for GnRH. The present study was conducted to investigate whether this reflects a transcriptional response to calcium pulse frequency, as determined by alterations in primary transcript (PT) expression. Perifused rat pituitary cells were given pulses of the calcium channel-activator Bay K 8644 (BK; with 10 mM KCl in the injectate) for 6 h. The response to alterations in pulse dose was examined by giving pulses of 1, 3, or 10 μM BK at 60-min intervals. Maximal increases in LHβ and FSHβ PTs were obtained with the 3-μM BK pulse dose and with the 10-μM dose for α. To investigate the effect of calcium pulse frequency, 3-μM BK pulses were given at intervals of 15, 60, or 180 min. Alpha PT was selectively stimulated by 15-min pulses and LHβ by 15- and 60-min pulses of BK. In contrast, FSHβ PT was maximally stimulated by the slower, 180-min pulse interval. These findings reveal that pulsatile increases in intracellular calcium stimulate α, LHβ, and FSHβ transcription in a differential manner. Thus, intermittent changes in intracellular calcium appear to be important in the transmission of GnRH pulse signals from the plasma membrane to the gene, and they may mediate the differential actions of pulse frequency on gonadotropin subunit gene expression.

Prenatal, perinatal, and childhood vitamin D exposure and their association with childhood allergic rhinitis and allergic sensitization

BACKGROUND The role of early-life vitamin D in childhood allergy is controversial. OBJECTIVE We sought to assess vitamin D exposure in early life by multiple modalities and ascertain its association with childhood allergic rhinitis and allergic sensitization. METHODS One thousand two hundred forty-eight mother-child pairs from a US prebirth cohort unselected for any disease were studied. Vitamin D exposure was assessed by measures of maternal intake during the first and second trimesters of pregnancy and serum 25-hydroxyvitamin D (25[OH]D) levels in mothers during pregnancy, cord blood, and children at school age (median age, 7.7 years; interquartile range, 1.0 years). Tests for associations between vitamin D exposure with ever allergic rhinitis, serum total IgE level, and allergen sensitization at school age were conducted. RESULTS The correlations between maternal intake of vitamin D during pregnancy and serum 25(OH)D levels in pregnant mothers, cord blood, and children at school age were weak to moderate (r = -0.03 to 0.53). Each 100 IU/d of food-based vitamin D intake during the first and second trimesters (equivalent to the amount of vitamin D in an 8-ounce serving of milk) was associated with 21% and 20% reduced odds of ever allergic rhinitis at school age (odds ratios of 0.79 [95% CI, 0.67-0.92] and 0.80 [95% CI, 0.68-0.93]), respectively. There were no associations between maternal supplemental vitamin D intake or serum 25(OH)D levels at any time point with ever allergic rhinitis. There were no associations between any vitamin D exposure and serum total IgE level or allergen sensitization at school age. CONCLUSIONS Inclusion of foods containing vitamin D in maternal diets during pregnancy may have beneficial effects on childhood allergic rhinitis.

IgE Antibody Detection and Component Analysis in Patients with Eosinophilic Esophagitis

BACKGROUND Although IgE antibodies to cows milk and wheat are common in patients with eosinophilic esophagitis (EoE), titers are low and responses to diet are not dependent on having IgE antibodies. OBJECTIVE To better define specific IgE antibody responses to foods, focusing on those foods that appear to play a role in EoE. METHODS Adult (n = 46) and pediatric (n = 51) patients with EoE were recruited for skin prick testing and serum measurement (whole and diluted) of IgE antibodies specific for aeroallergens, food extracts, and component allergens by ImmunoCAP. Immuno Solid-phase Allergen Chip analysis was also used to measure the specificity of IgE antibodies to 112 allergen molecules. RESULTS In adults and children, there was a higher prevalence of sensitization to food extracts by ImmunoCAP than by skin prick testing. Using Immuno Solid-phase Allergen Chip to assess the specificity of IgE antibodies to 112 allergen molecules, we found that results for food allergens were mostly negative. In contrast, ImmunoCAP assays for specific milk allergens gave positive IgE antibody results in 31 of 34 sera. The correlations between specific IgE antibody to Bos d 4 or Bos d 5 and milk extract were strong (R = 0.89 and 0.76, respectively; P < .001). The evidence that IgE antibodies to foods were directed at minor components of the extracts was further supported by measurements on diluted sera. CONCLUSIONS The IgE responses in cows milk-sensitized patients with EoE are frequently to whey proteins Bos d 4 and Bos d 5, minor components of the extract. These IgE assays may be able to identify the proteins that are relevant to EoE even though IgE is not the primary mechanism.