Diagnostic Decision Points of Specific IgE Concentrations in Korean Children With Egg and Cow's Milk Allergies

Purpose

The purpose of this study was to evaluate the utility of specific IgE (sIgE) concentrations for the diagnosis of immediate-type egg and cow''s milk (CM) allergies in Korean children and to determine the optimal cutoff levels.

Methods

In this prospective study, children ≥12 months of age with suspected egg or CM allergy were enrolled. Food allergy was diagnosed by an open oral food challenge (OFC) or through the presence of a convincing history after ingestion of egg or CM. The cutoff levels of sIgE for egg white (EW) and CM were determined by analyzing the receiver operating characteristic curves.

Results

Out of 273 children, 52 (19.0%) were confirmed to have egg allergy. CM allergy was found in 52 (23.1%) of 225 children. The EW-sIgE concentration indicating a positive predictive value (PPV) of >90% was 28.1 kU/L in children <24 months of age and 22.9 kU/L in those ≥24 months of age. For CM-sIgE, the concentration of 31.4 kU/L in children <24 months of age and 10.1 kU/L in those ≥24 months of age indicated a >90% PPV. EW-sIgE levels of 3.45 kU/L presented a negative predictive value (NPV) of 93.6% in children <24 months of age, while 1.80 kU/L in those ≥24 months of age presented a NPV of 99.2%. The CM-sIgE levels of 0.59 kU/L in children <24 months of age and 0.94 kU/L in those ≥24 months of age showed NPVs of 100% and 96.9%.

Conclusions

Our results indicate that different diagnostic decision points (DDPs) of sIgE levels should be used for the diagnosis of egg or CM allergy in Korean children. The data also suggest that DDPs with high PPV and high NPV are useful for determining whether OFC is required in children with suspected egg or CM allergy.     

Butter Tolerance in Children Allergic to Cow's Milk

We performed an oral food challenge (OFC) with 10 g of butter (equivalent of 2.9 mL cow''s milk) and 25-mL heated cow''s milk for 68 children with cow''s milk-allergy. Thirty-eight children reacted only to heated cow''s milk. Twenty-four children reacted to neither heated milk nor butter. Thirty-eight (86.4%) of 44 patients with positive results to the OFC for heated milk could safely tolerate butter. It is highly likely that even children with cow''s milk-allergy who show positive results to an OFC for heated milk can consume butter. The milk-specific IgE value indicative of a negative predictive value of over 95% was 17.8 kUA/L, and patients with low milk-specific IgE values may be able to safely consume butter. Including butter in the diets of patients with milk-allergy after a butter challenge may improve quality of life.     

Allergen-Specific IgE Antibodies against Antigenic Components in Cow Milk and Milk Substitutes

Crossed radioimmunoelectrophoresis (CRIE) was used to study the presence of serum IgE against antigenic components of cow milk in 21 selected milk-allergic patients. The amount of each IgE specificity was estimated by a scoring system. The milk-allergic children had mainly IgE against alpha-lactalbumin, beta-lactoglobulin, albumin and immunoglobulin, the four major proteins of bovine whey, as well as IgE against three casein components. A serum pool from 1000 normal adults had IgE against the same whey protein, but in smaller amounts, and no IgE against the casein components. Eight cow milk-based formulae, commonly used for infant feeding, and goat milk were studied by the same method. It was found that six of the milk substitutes did not differ significantly from cow milk in antibody binding, but the two hydrolysed casein products, Nutramigen and Pregestimil, consisted of such small molecules that the rabbit antisera could not precipitate the hydrolysed proteins in the gels on the CRIE plates. It was therefore not possible to study their IgE binding, if any, by this method.     

Relationship of Allergen-Specific IgE Antibodies, Skin Prick Tests and Allergic Disorders in Unselected Adolescents

The relationship between serum levels of allergen-specific IgE (RAST) and skin prick test reactivity and allergic disorders was evaluated in 137 subjects randomly selected from an adolescent population. All subjects were prick tested with six common allergens, interviewed and physically examined. In addition, serum was collected for RAST analysis with three to six allergens. At least one positive RAST result (score 1-4) was observed in 40% and at least two positive RASTs in 22% of the subjects. Boys experienced more RAST reactions and generally with higher scores than girls. For instance, 26% of boys but only 11% of girls were RAST positive to timothy grass pollen. The correlation between prick test and RAST results was better with pollens than with house dust and animal epithelia. When the test results were discordant, the skin test was usually positive and RAST negative. Many of the small skin reaction (weal diameter 3-4 mm) were accompanied by a negative RAST. Respiratory allergy was closely connected with both positive skin test and RAST reactivity, while atopic dermatitis was less related. In 17% of the adolescents positive skin tests and in 14% positive RASTs occurred in the absence of any allergic symptoms. We conclude that a positive RAST score 3-4 to inhaled allergens is a strong indicator of clinical allergy but low scores 1-2 are frequently found in healthy young people.     

IgE Cross-reactivity with Caseins from Different Species in Humans Allergic to Cow's Milk

Fifty-eight sera from humans allergic to cow's milk proteins were analysed for the specificity of their IgE response to the whole casein fraction of milk from different ruminant and nonruminant species (e.g. cow, sheep, goat, rabbit and rat). IgE-specific responses were determined by an enzyme allergosorbent test using the purified casein fractions as immobilized antigen and an anti-human IgE monoclonal antibody labelled with acetylcholinesterase. Co-and/or cross-sensitizations to caseins of the different ruminant species occurred extensively, though IgE responses to ovine and caprine casein appeared to be lower than that obtained with bovine casein. Cross-reactivity is suggested by the significant reactivity of rat and rabbit casein toward human IgE. In terms of specificity and intensity, the IgE response to caseins demonstrates a great variability. Structural homologies in caseins of such different species, that can share common epitopes for the IgE of some patients, suggest that prevention of cow's milk allergy cannot be achieved by using milk from other species as substitutes.     

Birch Pollen Allergy in Children Role of Milk Feeding during the First Birch Season of Life

The effect of exclusive breast-feeding throughout the first birch pollen season of life was examined in 59 children compared to 67 children on cow milk formula and to 27 children weaned to cow milk-based formula duting theit first birch season. The infants were about 3 months of age in their first birch season, and allergy to birch pollen was evaluated at 5 years of age by history and prick and provocation tests. Breast-feeding throughout the first birch season did not prevent birch pollen alletgy; a similar birch alletgy prevalence of about 10% was found in children initially fed on human or cow milk. Instead. weaning to cow milk-based formula during the first birch season seemed to protect from subseauent development of birch pollen allergy. Analogous results were obtained regarding allergy to grass pollen. This unexpected finding may be related to the immunological stress on the young infant provided by introduction of cow milk proteins at an early age.     

Adult onset of cow's milk protein allergy with small-intestinal mucosal IgE mast cells

We report a female patient with adult onset of cow's milk protein allergy. For 1 year, she experienced repeated gastrointestinal symptoms and had a single exercise-induced anaphylactic reaction. In addition to positive skin tests and specific IgE to milk proteins and a positive challenge test, immunohistochemistry of the small intestine showed a marked increase of IgE-positive mast cells. This finding is highly specific and could provide an additional tool for diagnosing cow's milk protein allergy and possibly also other food allergies.     

Fel d 4, a cat lipocalin allergen

BACKGROUND: Cat allergy is unique among allergy to mammals in that the major allergen Fel d 1 is a uteroglobin-like protein and not a lipocalin. The biochemical spectrum of the cat allergens is thus uncertain, particularly with regard to the role that a cat lipocalin protein may play in sensitization to cats in allergic individuals. OBJECTIVE: To analyse cDNA encoding a lipocalin allergen and the corresponding recombinant allergen at both the molecular and immunological levels. METHODS: A submandibular salivary gland cDNA expression library was constructed and screened for clones producing IgE-binding polypeptides. cDNA encoding a lipocalin allergen and its corresponding recombinant allergen were analysed. RESULTS: An IgE binding molecule with high sequence identity to the boar salivary lipocalin and the horse lipocalin Equ c 1 allergen was isolated and designated, Fel d 4. Serum from 62.96% of cat-allergic subjects examined had measurable IgE antibody to Fel d 4 but typically at low levels. Despite this in 47% of sera the anti-Fel d 4 IgE titres were higher than the anti-Fel d 1 titres. IgE binding to the lipocalin allergen could be blocked by an allergen extract from cow and to a lesser degree by extracts from horse and dog. CONCLUSION: Fel d 4 is a lipocalin allergen produced by the cat, which binds IgE at relatively high frequency in cat-sensitive individuals. The allergen provides not only a means for investigating differences in the immune response to lipocalin allergens from that found for other mammalian species but also an important reagent for the diagnosis of cat allergy.     

Specific monoclonal antibodies and human immunoglobulin E show that Hev b 5 is an abundant allergen in high protein powdered latex gloves

BACKGROUND: Hev b 5 is a major latex allergen recognized predominantly by latex-allergic health care workers (HCWs). Recombinant Hev b 5 (rHev b 5) was previously expressed as a fusion protein with maltose binding protein (MBP), itself an immunogenic molecule; therefore non-fusion rHev b 5 is desirable. Moreover, standardized immunological assays for the detection of Hev b 5 are currently lacking and may have important implications for both allergen avoidance and diagnosis in latex allergy. OBJECTIVES: To generate and use Hev b 5-specific mAbs to determine the relative abundance of Hev b 5 in different latex extracts, correlating this with the IgE reactivity of latex-allergic HCWs and to produce non-fusion rHev b 5. METHODS: For the production of mAbs, mice were immunized with rHev b 5/MBP fusion protein and mAbs selected with rHev b 5/MBP but not MBP reactivity. The mAb reactivity was compared with polyclonal IgE from latex-allergic HCWs using direct and inhibition ELISA and immunoblot assays. Recombinant Hev b 5 was expressed and purified in the pPROEX-HTa bacterial expression system. RESULTS: Four Hev b 5-specific mAbs were produced. Immunoblotting and ELISA using the mAbs indicate abundant Hev b 5 in high protein powdered latex glove extracts as compared with crude latex sap extracts. High quality surgical gloves with no detectable protein have no detectable Hev b 5. Inhibition ELISAs using serum IgE from latex-allergic HCWs and Hev b 5-specific mAbs gave strong correlation. Non-fusion recombinant Hev b 5 was successfully expressed and purified, showing reactivity with both the Hev b 5-specific mAbs and serum IgE of latex-allergic HCWs. CONCLUSION: Hev b 5-specific mAbs and human IgE from latex-allergic HCWs demonstrate the greater content of Hev b 5 in high protein powdered glove extracts. This may explain the observed higher frequency of sensitization to this allergen in HCWs.     

过敏性鼻炎患儿过敏原特异性IgE检测与临床意义

目的 了解过敏性鼻炎儿童主要过敏原分布情况及特点,以指导临床防治.方法 采用免疫印迹法体外定量检测患儿血清中特异性IgE抗体及20种常见过敏原.结果 938例过敏性鼻炎患儿中,100%至少对一种以上的过敏原呈阳性反应,其中487例患儿总IgE〉400IU/Ml,230例患儿总IgE在200IU/ml~400IU/ml之间.在检测20种过敏原中以户尘螨和屋尘的阳性率最高（90.0%,80.8%）.结论 过敏性鼻炎患儿至少有一种特异性IgE抗体显著增加,户尘螨、屋尘、动物皮屑、羊肉和牛奶是引起儿童过敏性鼻炎的主要过敏原.儿童在春秋温暖季节易发过敏性鼻炎.     

Allergic reactions to raw, pasteurized, and homogenized/pasteurized cow milk: a comparison

Five children aged 12-40 months with IgE-mediated adverse reactions to cow milk (immediate onset clinical pattern of cow milk allergy) were orally challenged double-blind in random order with three different milk preparations processed from the same batch of milk 1) raw untreated cow milk, 2) pasteurized cow milk, 3) homogenized and pasteurized cow milk, and 4) Nutramigen (a commercial hypoallergenic infant formula based on hydrolysed casein) as placebo. Skin prick tests with the same preparations were also performed. On oral challenge the three different processed milk types provoked significant and similar allergic reactions in each child, and no adverse reactions followed the challenge with placebo (Nutramigen). Skin prick test with the same milk products were positive in all children and comparable to the results with an extract of purified raw cow milk protein (Soluprick), whereas Nutramigen did not elicit any skin reactions. A tendency towards a lower threshold of reaction and larger skin reactions induced by the processed milk preparations might indicate an increased ability of pasteurized and homogenized/pasteurized milk to evoke allergic reactions in patients allergic to milk.     

Usefulness of Measurement of Antibodies in Serum in Diagnosis of Sensitivity to Cow Milk and Soy Proteins in Early Childhood

A noteworthy feature of this study is that comparisons were made between specific, sensitive, quantitative measurements of serum antibodies to food proteins and objective appraisal of clinical manifestations buy double-blind food challenges. Over 50 children, 4–30 months of age, with suspicious histories of adverse reactions to cow milk or soy products were investigated. Levels of serum antibodies to cow-milk proteins were clearly higher in children with adverse reactions to milk, confirmed by blind challenge; there was no overlap with the lower levels of serum antibodies in children without confirmed reactions. Findings with serial determinations of serum antibodies to cow milk in selected cases are also presented.
The levels of serum antibodies evoked by cow milk and soy formulae fed from birth until 4 months of age were similar. The levels of serum antibodies to soy protein in children with and without adverse reactions to soy products were not definitive.
The bearing of these data on the comparative "antigenicity" of cow milk and soy products and the distinction between asymptomatic and clinically significant, symptomatic, sensitivity are discussed.     

过敏性哮喘患者痰中粉尘螨特异性IgE和总IgE检测

本文用BA-ELISA测定100例过敏性哮喘患者的痰和血清中粉尘螨特异性IgE和总IgE,结果表明,68例粉尘螨过敏性哮喘患者的痰和血清中特异性IgE、总IgE水平高于32例非粉尘螨过敏性哮喘患者,两者有非常显著性差异(P<0.001)。在粉尘螨过敏性哮喘患者痰中特异性IgE、总IgE亦明显高于血清。选择22例哮喘患者经减敏治疗半年后,多数病例痰和血清中特异性IgE、总IgE均有下降,治疗前后差异显著(P<0.001)。     

Allergic symptoms up to 4–6 years of age in children given cow milk neonatally A prospective study

In a previously published prospective study, we followed the development of allergic symptoms in term infants with a slightly reduced birthweight (-1 SD to -2 SD). These children received, according to local routine, early feeding with cow milk formula in order to diminish such neonatal problems as hypoglycemia and hyperbilirubinemia. Of 216 infants 207 were observed for allergic symptoms up to 18 months of age. One group (F) received cow milk formula during the first days of life before the mother's breastmilk production started and was then breastfed; the other (B) was not given any formula before normal breastfeeding started. Unexpectedly, we found fewer allergic symptoms, in particular allergic skin problems, in the group fed cow milk, the difference being concentrated to children with a family history of allergic symptoms. At 5 years of age 183 of the 207 children have been reinvestigated. Mild symptoms of allergy (suspected and obvious) were found in 22% (F) and 27% (B) respectively (NS). Moderate and severe symptoms of allergy (obvious) were found in 4.2% (F) and 4.5% (B). In the subgroup with a double family history of allergic symptoms, 28% (7/25, F) and 59% (10/17, B) had symptoms of allergy (p less than 0.05). This difference was even more pronounced when laboratory tests in favour of atopic diagnosis were included, 14% (F) and 53% (B) respectively (p less than 0.05). Thus at 5 years we still find a significantly lower frequency of allergic symptoms in the subgroup fed cow milk formula early with a family history of allergic symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

过敏性鼻炎患者总IgE、嗜酸性粒细胞和特异性IgE结果分析

目的 探讨血清总IgE(immunoglobulin E,IgE)水平及外周血嗜酸性粒细胞(eosinophil,EOS)计数在过敏性鼻炎(allergic rhinitis,AR)诊断中的作用,以及两者与血清特异性IgE(specific immunoglobulin E,sIgE)水平之间的关系。方法选择对蒿属花粉过敏的过敏性鼻炎患者60例作为鼻炎组,60例健康人作为对照组。将鼻炎组分为男性组与女性组,青年组(18~40岁)与中年组(41~65岁),将鼻炎组患者根据sIgE结果分为:中低水平(0.35 IU/mL≤sIgE<3.5IU/mL)、高水平(3.5 IU/mL≤sIgE<17.5 IU/mL)与极高水平(sIgE≥17.5 IU/mL)。结果 鼻炎组总IgE水平和EOS计数均高于对照组,差异有统计学意义( P <0.05);鼻炎组、男性组、女性组、青年组和中年组总IgE与sIgE均成正相关( r s =0.541,0.490,0.599,0.566,0.462,均 P <0.05);鼻炎组患者总IgE与sIgE等级成正相关( rs =0.449, P <0.05)。结论 血清总IgE可作为AR诊断辅助指标,联合检测血清总IgE及sIgE可为AR的诊断提供更充分的依据。     

过敏原蛋白组分sIgE检测及分析

目的 分析过敏性疾病患者血清中多种过敏原蛋白组分的sIgE,明确过敏原中的致敏蛋白组分,为临床过敏性疾病预防和治疗提供科学依据.方法 采用荧光酶联免疫法,用ImmunoCAP过敏原检测试剂检测受试者血液标本中过敏原蛋白组分及相关过敏原的特异性IgE(sIgE)水平,统计每种过敏原蛋白组分sIgE检出量和阳性率,并对主要致敏蛋白组分sIgE阳性率和相关过敏原的阳性率进行对比和分析.结果 40种过敏原蛋白组分的阳性率均小于过敏原的阳性率,致敏组分和交叉过敏组分共存于过敏原中.户尘螨、黄胡蜂毒、桃、猫毛、榛子、牛奶和鸡蛋的主要致敏蛋白组分阳性率高于过敏原阳性率的50%;百慕达草、意大利蜜蜂毒、桦树和花生的主要致敏蛋白组分阳性率介于过敏原阳性率的20%~50%之间;虾、狗毛、梯牧草和北艾草的主要致敏蛋白组分阳性率低于过敏原阳性率的20%.结论 过敏原蛋白组分检测能鉴别过敏原中真正致敏的蛋白组分,解决由于交叉反应所导致的过敏原特异性诊断难题,确保过敏性疾病特异性免疫治疗的精确性和有效性.     

Diagnosis and Rationale for Action Against Cow's Milk Allergy (DRACMA): a summary report

The 2nd Milan Meeting on Adverse Reactions to Bovine Proteins was the venue for the presentation of the first consensus-based approach to the management of cow's milk allergy. It was also the first time that the Grading of Recommendations, Assessments, Development, and Evaluation approach for formulating guidelines and recommendations was applied to the field of food allergy. In this report we present the contributions in allergen science, epidemiology, natural history, evidence-based diagnosis, and therapy synthesized in the World Allergy Organization Diagnosis and Rationale for Action against Cow's Milk Allergy guidelines and presented during the meeting. A?consensus emerged between discussants that cow's milk allergy management should reflect not only basic research but also a newer and better appraisal of the literature in the light of the values and preferences shared by patients and their caregivers in partnership. In the field of diagnosis, atopy patch testing and microarray technology have not yet evolved for use outside the research setting. With foreseeable breakthroughs (eg, immunotherapy and molecular diagnosis) in the offing, the step ahead in leadership can only stem from a worldwide organization implementing consensus-based clinical practice guidelines to diffuse and share clinical knowledge.     

Breast Feeding, Cow Milk Feeding, and Allergy

Information about every 10th child aged 14 to 38 months was collected by means of a questionnaire in Turku, Finland in March, 1983. This paper reports on the occurrence of allergy in relation to the duration of breast feeding and to the age of the child when cow milk feeding was started. The average duration of breast feeding was 5.7 months and the average age at the introduction of cow milk-based products was 4.3 months. Allergy was reported in family members of 47.6% of the children. In 30.3% the child himself was reported allergic. The occurrence of allergy was unaffected by the duration of breast feeding and the age at introduction of cow milk feeding.