Development and properties of hypoallergenic infant formula

Milk proteins are composed of casein, further classified into αS1-casein, αS2-casein, β-casein, and κ-casein, and whey protein, which is separated into α-lacatalbumin, β-lactoglobulin, serum albumin, and some minor proteins, such as lactoferrin and immunoglobulin. To reduce the allergenicity of protein, heat treatment and enzymatic protein hydrolysis by endopeptidase are necessarily required. Additionally, membrane technology should be applied to produce a protein hydrolyzate, which has consistent molecular weight of peptide and low in free amino acid without allergenic peptide or protein. Extensive casein hydrolyzate and whey protein hydrolyzate are used for protein source of mainly extensively hydrolyzed protein formula (eHF) intended for the treatment of cow’s milk allergy. Also, partially hydrolyzed formula (pHF) is developed, which is using a single protein source e.g., whey protein hydrolyzate. The allergenicity of infant formula can be determined according to molecular weight profile and antigenicity reduction compared to intact protein. More than 90% peptides are present in eHF have a molecular weight of <3,000 Da. Peptide molecular weight profiles of pHF range mainly between 3,000 and 10,000 Da, but have a small percentage of >10,000 Da. Generally, antigenicity reduction in eHF and pHF is 10-6 and 10-3, respectively. Even if protein hydrolyzate is manufactured under strict quality control, there is still a risk of cross contamination of allergenic milk components through environmental conditions and the shared manufacturing process. Thus, quality assessment of protein hydrolyzate formula must be performed routinely.ope

A Case Report of Food-Dependent Exercise-Induced Anaphylaxis in a Patient who was Sensitive to Pork.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a specific variant of exercise-induced anaphylaxis that requires both vigorous physical activity and the ingestion of specific foods. In particular, it is rare occurrence for FDEIA to be associated with meat in Korea. A 15-year-old female had generalized urticaria, dyspnea, severe cough, headache, dizziness, and vomiting after singing and dancing for 1 hour and after ingesting grilled pork. Skin prick tests showed a strong positive reaction to pork, whereas the results of an oral food challenge and exercise provocation tests were negative. However, the exercise provocation test after pork ingestion showed a positive reaction manifested by generalized urticaria, cough, mild dyspnea, and a 23% decreased peak expiratory flow rate. Three allergens to pork (67 kDa, 90 kDa, and 15 kDa) reacted with the patient's serum on immunoglobulin E immunoblotting. We report a case of pork-dependent exercise-induced anaphylaxis in a patient who was sensitive to pork.ope

A Nationwide Clinical Study of Acute Respiratory Distress Syndrome in Children

Purpose : Acute respiratory distress syndrome(ARDS) is the final course of acute lung injury. It results from various etiological origins and pathophysiologic mechanisms, and has a mortality rate of approximately 60-70%. Although the confirmative incidence of ARDS in children is yet unknown, the increasing incidence of ARDS has been reported in Korea. In the present study, we report ARDS diagnosed at the Clinic for Pediatric Allergy and Respiratory Disease in eleven medical centers nationwide. Methods : The study was conducted on 42 patients diagnosed with ARDS in Pediatric Allergy and Respiratory Clinics from January, 1995 to August, 1997. We analyzed the clinical course and treatment modalities of the 42 cases of ARDS retrospectively. Results : The total number of patients recruited was 42, including seventeen(40.4%) below 1-year-old. The mean age was 2.0¡¾2.3(mean¡¾standard deviation) years with a range of 2 months to 10 years, and there was no sex predominance(male/female : 27/15). Twenty-one cases(50.0%) occured during the spring(March, April and May). The major triggering factors of ARDS were viral pneumonia(59.5%) and bacterial pneumonia (19.1%). Mechanical ventilation was used in 37 cases(88.1%). Major complications included pneumothorax, DIC, and gastrointestinal bleeding. The mortality rate was 61.9% of which 16 case (61.5%) occurred before 2 years of age. Concldusion : We conducted this study to make a rapid diagnosis and appropriate treatment of ARDS in children, who have major risk factors, to reduce its mortality rate.ope

Can Allergen-Specific IgE Antibodies Diagnose Egg Allergy Accurately?

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Changes in Allergenicity of Porcine Serum Albumin by Gamma Irradiation

Pork is an excellent source of essential nutrients such as protein. However, pork can trigger hypersensitivity and serum albumin of pork is known as major allergen. In this study, to evaluate the effect of gamma irradiation on the allergenicity of porcine serum albumin (PSA), PSA solution was irradiated at 3, 5, 7, 10, 15, and 20 kGy. The changes in the ability of PSA to bind IgG and patient's serum caused by gamma irradiation were observed by ci-ELISA and immunoblotting. SDS-PAGE was used for measuring the conformational change of gamma-irradiated PSA. The ability of 3-kGy-irradiated PSA to bind p-IgG and patient's serum was decreased to 30% and 15%, respectively. The binding ability showed no significant differences among all irradiated samples. SDS-PAGE showed that the irradiated PSA bands were degraded and aggregated. Immunoblotting of irradiated PSA revealed that IgG and patient's serum were rarely recognized at 3 kGy. Therefore, gamma irradiation could be applied to less-allergenic pork productsope

Roles of Bcl-2 and caspase-9 and -3 in CD30-induced human eosinophil apoptosis

BACKGROUND/PURPOSE: Activation of cell surface CD30 by immobilized anti-CD30 monoclonal antibodies (mAb) induces strong apoptosis in human eosinophils. This anti-CD30 mAb-induced eosinophil apoptosis is inhibited by the addition of inhibitors of p38, ERK1/2 mitogen-activated protein kinases, and phosphatidylinositol 3-kinase. However, there is little data investigating the role of Bcl-2 and caspases in eosinophil apoptosis induced by anti-CD30 mAb. We sought to determine whether anti-CD30 mAb induces human eosinophil apoptosis via Bcl-2 and caspase pathways. METHODS: Peripheral blood was drawn from 37 healthy volunteers. The CD30 expression on eosinophils was measured at various time points. Eosinophils were then cultured in plates precoated with anti-CD30 mAb (clone Ber-H8), isotype control immunoglobulin G1, interleukin (IL)-5, or dexamethasone. Western blot analysis was performed to determine the expression of Bcl-2, procaspase-8, -9, and -3, and caspase-8, -9, and -3 after cross-linking of CD30. Human eosinophils were also cultured in plates precoated with anti-CD30 mAb (clone Ber-H8) in the presence or absence of caspase-9 or -3 inhibitors. Eosinophil apoptosis was assessed using flow cytometry. RESULTS: The addition of anti-CD30 mAb significantly increased eosinophil apoptosis compared with controls. In western blot analysis, the addition of anti-CD30 mAb significantly decreased the expression of Bcl-2 and procaspase-9 and -3 and increased the expression of caspase-9 and -3. The addition of caspase-9 or -3 inhibitors decreased anti-CD30 mAb-induced human eosinophil apoptosis. Procaspase-8 or caspase-8 expression was not changed in response to various stimuli. CONCLUSION: Anti-CD30 mAb-induced human eosinophil apoptosis is likely to be mediated through Bcl-2 and caspase-9 and -3.ope

Toll-like receptor 9 expression and interferon-alpha secretion upon CpG-ODN stimulation in allergic subjects

PURPOSE: The aim of this study is to explore the effect of the Toll-like receptor 9 (TLR9) expressed in plasmacytoid dendritic cells (pDCs) that respond to antigen to Th2 immune deviation in allergic patients. METHODS: Subjects consisted of 19 allergic patients and 17 healthy volunteers. Skin prick tests and nasal provocation tests were performed for the two groups. Peripheral blood mononuclear cells (PBMCs) were collected from subjects and analyzed for the Lineage Cocktail (CD3, CD14, CD16, CD19, CD20, CD56) (-), HLA-DR (+), and CD123 (+) using flow cytometry. In addition, we analyzed TLR9 mRNA by reverse transcriptase-polymerase chain reaction. The level of interferon-alpha (IFN-alpha) of the PBMCs following stimulation with the TLR9 ligand CpG-ODN 2216 was also evaluated. RESULTS: Analyses of CD123 (+) revealed a nearly similar distribution for the classical pDC markers in the allergic group (0.1%+/-0.04%) and in the controls (0.25%+/-0.23%). The mRNA levels of TLR9 on PBMCs were not different between the allergic group and the controls (1.29+/-0.41 vs. 1.25+/-0.23, respectively). Additionally, the level of IFN-alpha in PBMCs exposed to stimuli of the TLR9 ligand CpG-ODN 2216 was not significantly different between the two groups (911+/-829 vs. 1,095+/-888 pg/mL, respectively). CONCLUSIONS: We found no evidence that TLR9-dependent immune responses in human pDCs are associated with allergic statusope

Food allergen sensitization in young children with typical signs and symptoms of immediate-type food allergies: a comparison between monosensitized and polysensitized children

PURPOSE: The clinical interpretation of children sensitized to allergens is challenging, particularly in children with food allergies. We aimed to examine clinical differences between children with monosensitization and those with polysensitization to common food allergens and to determine risk factors for polysensitization in young children <10 years of age with immediate-type food allergies. METHODS: The study included children <10 years of age with signs and symptoms indicative of immediate-type food allergies. Serum total IgE level was measured, and ImmunoCAP analysis for food allergens was performed. RESULTS: The mean age of the study subjects was 1.6±1.6 years (75 boys and 51 girls). Thirty-eight children (30.2%) were monosensitized and 88 children (69.8%) were polysensitized. Multivariate logistic regression analysis showed that the development of polysensitization to common food allergens was positively associated with a parental history of allergic rhinitis (adjusted odds ratio [aOR], 6.28; 95% confidence interval [CI], 1.78-22.13; P=0.004), season of birth (summer/fall) (aOR, 3.10; 95% CI, 1.10-8.79; P=0.033), and exclusive breastfeeding in the first 6 months of age (aOR, 3.51; 95% CI, 1.20-10.25; P=0.022). CONCLUSION: We found significant clinical differences between children with monosensitization and those with polysensitization to common food allergens and identified risk factors for the development of polysensitization in young children with immediate-type food allergies. Clinicians should consider these clinical risk factors when evaluating, counseling, treating, and monitoring young children with food allergies.ope

The Prevalences of Asthma and Allergic Diseases in Korean Children

Asthma and allergic diseases are one of the most common disorders in children. Due to its increased prevalence, as well as the increased morbidity and mortality from these diseases, asthma and allergic diseases have come to be recognized as a major worldwide public health issue. In addition, socioeconomic burden of asthma and allergic diseases also has increased in Korea. The International Study of Asthma and Allergies in Childhood (ISAAC) investigated the world-wide prevalence of asthma and other allergic diseases using simple standardized methods because of the comparison of asthma and allergic diseases between the countries. In Korea, several epidemiologic studies have been conducted to determine the prevalence of asthma in children. Although these studies showed increased prevalence of asthma among Korean children (from 3.4% in 1964 to 10.1% in 1989), these findings were based on data from small numbers of subjects. The first Nationwide Study of Asthma and Allergies in Korean Children, which utilized the Korean version of ISAAC written and video questionnaire, was conducted in 1995 and the second Nationwide Study of Asthma and Allergies in Korean Children was conducted in 2000, directed by the Korean Academy of Pediatric Allergy and Respiratory Diseases. We report here the prevalence of asthma and other allergic diseases in Korean children and adolescents, and show the changes that occurred over this 5 year period. We also describe the risk factors for development of these diseases in Korean children. We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 25,117 children selected from 34 elementary school and 14,946 children selected from 34 middle school across the nation, the response rate was 94.8%. In 2000, 27,831 children selected from 34 elementary school and 15,214 children selected from 34 middle school, and the response rate was 96.4%. From these studies, we can confirm that increase of the prevalences of asthma, allergic rhinitis, and atopic dermatitis in Korea, except the prevalence of food allergy. Especially, the video questionnaire showed increases in the lifetime and 12 month prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time in middle school children. In addition, the increase of prevalences of symptoms, diagnosis and treatment of atopic dermatitis was noted significantly. Risk factor analysis showed that body mass index (BMI), passive smoking and living with a dog or cat were associated with higher risk of wheeze. Also the occurrence of fever during infancy and the frequent use of antibiotics were associated with the risk of wheeze. In conclusion, during the 5 year period from 1995 to 2000, the prevalences of asthma, allergic rhinitis, and atopic dermatitis has increased in Korean children. BMI, passive smoking, living with a dog or cat, the fever episodes in infancy, and the frequent use of antibiotics in infancy are important risk factors to development of asthma and atopic dermatitis. In the near future, the birth cohort study will be needed to investigate the causes of this increase and the natural course of allergic diseases, then we develop the methods to control asthma and allergic diseasesope

Reduction of Allergenicity of Domestic Pork Ham and Bacon by Autoclave Treatment

The pork hams and bacon comprising the most popular processed pork were treated with autoclave to investigate application of hypoallergenic pork. Among pork hams and bacon, two products with the highest binding ability were selected for experiments. The results of ci-ELISA on pork hams treated with autoclave showed that the binding ability of p-IgG and pigallergic patient's sera (P2) to PSA (porcine serum albumin) from pork ham samples by autoclave treatment at 121℃ for 30 min was slightly decreased. The binding ability to p-IgG of b and c bacon treated with autoclave was declined to below 16% and 11% as compared with control sample that showed 60% and 91% binding ability. The binding ability to P2 of b and c bacon treated with autoclave decreased to below 22% and 34% as compared with control sample that showed 95% and 126% binding ability. A result of immunoblotting on bacon showed that p-IgG as well as pig patient's sera did not recognize PSA well in autoclave treatment. The results obtained from this work indicated that autoclave treatment was effective for a reduction of allergenicity of pork hams and bacon. Therefore the autoclave treatment may be applied to development of hypoallergenic porkope