ovalbumin and Milk-Hypersensitivity

Tolerance to allergens may partly depend on allergen-specific IgG and IgG subclasses and IgA antibodies. We investigated whether specific IgG and IgG subclasses and IgA antibodies to β-lactoglobulin, α-casein, and ovalbumin differed between infants who had verified cow's milk allergy (CMA) and infants with cow's milk (CM)-associated eczema, but negative CM oral challenge. The study population comprised 95 infants with clinical eczema that was by history associated with the consumption of CM. After an elimination period, a double-blind, placebo-controlled (DBPC) CM oral challenge confirmed CMA in 45 infants. Skin prick tests (SPT) were performed with CM and hen's egg. Serum levels of IgE antibodies to CM and hen's egg were measured with UniCAP (Phadia, Uppsala, Sweden), and levels of IgA, IgG, IgG1, and IgG4 antibodies to β-lactoglobulin, α-casein, and ovalbumin were measured with enzyme-linked immunosorbent assay. We observed that infants with CMA had lower IgG4 levels to β-lactoglobulin than infants with negative DBPC CM challenge (p = 0.004). Positive CM SPT was associated with lower IgG4 levels to α-casein (p = 0.04). The relation of CM IgE to β-lactoglobulin and α-casein IgG4 was higher in CMA than in infants with negative challenge (p < 0.002 and 0.0001). Positive egg SPT was associated with elevated levels of specific IgG to ovalbumin, β-lactoglobulin, and α-casein as well as IgA to α-casein (p < 0.04). Our study thus shows that low β-lactoglobulin-specific serum IgG4 levels may differentiate eczematous infants with CMA from infants who have eczema with only suspected association with CM.

Topics: Animals; Caseins; Eczema; Female; Humans; Immunoglobulin A; Immunoglobulin G; Infant; Lactoglobulins; Male; Milk Hypersensitivity; Ovalbumin; Skin Tests

Humoral responses to food antigens may reflect the propensity of a child's immune system to develop tolerance to innocuous antigens. Early nutrition as well as probiotics may influence these immunological responses.. To study the association of humoral responses to early food antigens with the administration of prebiotics and probiotics, with the occurrence of allergy, and with the length of exclusive breastfeeding.. In a randomized double-blind allergy prevention trial in high-risk children, 1018 mothers took probiotics or placebo from the 36th week of gestation, and their newborn infants received probiotics and prebiotics or placebo during 6 months. At 2 and 5 years, we evaluated the cumulative incidence of allergic diseases (food allergy, eczema, asthma, rhinitis) and sensitization (skin prick test ≥3 mm or serum antigen-specific IgE>0.7 kU/L). In 688 infants at age 2, we measured in sera-specific IgA, IgG, IgG1, and IgG4 antibody levels to cow's milk (CM), α-casein (CAS), β-lactoglobulin (BLG), and ovalbumin (OVA) with ELISA, and specific IgE levels to CM and hen's egg with UniCap.. Probiotic treatment (n=342) compared with placebo (n=346) showed no effect on serum food-specific IgA, IgG, IgG1, or IgG4 concentrations at age 2. Atopic children had higher OVA-IgA (P<0.001), OVA-IgG (P=0.001), OVA-IgG1 (P<0.001), and egg-IgE but lower OVA-IgG4/egg-IgE ratio (P<0.001) than non-atopic children. Longer duration of exclusive breastfeeding (≥4 vs. <4 months) was associated with reduced CM- and CAS-specific serum IgA (P<0.001) and IgG levels (P<0.001; P=0.003).. Allergy was associated with more intense IgA and IgG responses to OVA. Breastfeeding depressed humoral responses, whereas prebiotics and probiotics supplementation showed no immunomodulatory effect. The effect of probiotics on allergies is not mediated through food-specific antibody responses. Furthermore, OVA-specific IgA and IgG antibodies may help in assessing the risk for atopy.

Topics: Animals; Antibody Specificity; Breast Feeding; Cattle; Child, Preschool; Double-Blind Method; Female; Food Hypersensitivity; Humans; Hypersensitivity, Immediate; Immunoglobulin A; Immunoglobulin G; Infant; Infant, Newborn; Male; Milk Hypersensitivity; Milk Proteins; Ovalbumin; Prebiotics; Probiotics

Evaluating the gastrointestinal (GI) fate of proteins is part of the assessment to determine whether proteins are safe to consume. In vitro digestion tests are often used for screening purposes in the evaluation of potential allergenicity. However, the current pepsin resistant test used by the European Food Safety Authority, only corresponds to fasted gastric conditions representative of a late phase adult stomach. In addition, these tests are performed on isolated proteins and the effect of the food matrix and processing are not systematically considered. The aim of this research is to compare three different static in vitro GI scenarios that are physiologically relevant. Namely, an infant, early phase (fed state) adult and late phase (fasted state) adult model. These protocols are applied to well-characterised isolated dairy (β-lactoglobulin and β-casein) and egg (lysozyme and ovalbumin) proteins and the impact of food matrix/processing on their proteolysis is also investigated. A combination of SDS-PAGE, LC-MS/MS and spectrophotometric assay was used for the evaluation of the proteolysis. Results highlight differences across the three GI scenarios whether on isolated proteins or within food matrices. The infant model led to incomplete digestion, leaving intact egg proteins, either isolated or in the food matrix, and intact β-lactoglobulin in the milk. In addition, peptides greater than 9 amino acids were found throughout the intestinal phase for all proteins studied, regardless of the scenario. This reinforces the difficulty of linking protein digestibility to potential allergenicity because many other factors are involved that need further investigation.

Topics: Adult; Caseins; Digestion; Egg Hypersensitivity; Egg Proteins, Dietary; Fasting; Gastrointestinal Tract; Humans; In Vitro Techniques; Infant; Lactoglobulins; Milk Hypersensitivity; Milk Proteins; Models, Biological; Muramidase; Ovalbumin; Pepsin A; Peptides; Proteolysis

Topics: Acid Phosphatase; Animals; Enzyme-Linked Immunosorbent Assay; Female; Food Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Injections, Intraperitoneal; Mice, Inbred BALB C; Milk Hypersensitivity; Milk Proteins; Ovalbumin; Plant Roots; Solanum tuberosum; Time Factors

METHODS for predicting the clinical outcome of specific oral immunotherapy (OIT) would improve the safety of the therapy.. We investigated 40 children aged 6-17 years with IgE-mediated cow's milk allergy (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy due to adverse reactions (n = 8). From sera drawn before and after OIT, we analyzed specific IgA, IgG, IgG1 and IgG4 to cow's milk (CM), casein, β-lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher Scientific CAP system)]. As a reference, we also analyzed serum samples from 8- to 9-year-old children who either had no history of CMA (n = 76) or who had spontaneously recovered from IgE-mediated CMA (n = 56).. Levels of specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to OIT were higher in children who discontinued the therapy than in those who achieved desensitization (p < 0.05). Adverse reactions in the entire population were associated with low IgG and IgG4, but high IgG1 levels to ovalbumin (p < 0.05). Specific IgA, IgG, IgG1 and IgG4 to CM proteins significantly increased and IgE to CM decreased during OIT in children who achieved desensitization (p < 0.01). In those who discontinued OIT, only IgG, IgG1 and IgG4 to CM increased significantly (p < 0.03) and CM IgE remained unchanged.. High specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict failure to achieve desensitization in CM OIT. Specific IgA and IgG-class antibodies to CM increase and CM IgE decreases during desensitization.

Topics: Administration, Oral; Adolescent; Animals; Caseins; Child; Desensitization, Immunologic; Female; Humans; Immunoassay; Immunoglobulin A; Immunoglobulin G; Kinetics; Lactoglobulins; Male; Milk; Milk Hypersensitivity; Ovalbumin; Treatment Outcome

Epidemiological studies have shown an association between the consumption of raw farm milk and reduced incidence of allergy. In the present study, we fed untreated raw milk, gamma-sterilised milk, heat-treated milk or water to mice and compared their responses to allergen exposure and challenge treatment in a mouse model of gastrointestinal allergy. From weaning (3 weeks old), groups of BALB/c female mice (n 8) received raw milk, gamma-sterilised milk, heated milk or water via drink bottles, with the control group receiving water. All mice were fed a standard (dairy protein-free) rodent diet. At 6 and 8 weeks, groups were given intra-peritoneal injections with ovalbumin (OVA)/alum to sensitise them to the antigen. Controls were sham immunised. At week 10, mice were fasted and challenged four times on alternate days by intra-gastric administration with 50 mg OVA or saline. Levels of bacteria and milk proteins were assessed in milk samples. Mouse serum levels of specific IgE, IgG1 and IgG2a antibodies and mouse mast cell protease-1 (MMCP-1) were determined. Cytokine responses to 48 h activation with OVA were measured in cultured splenocytes from mice. Sterilised and heated milks contained no viable bacteria and reduced detectable levels of many milk proteins, in contrast to raw milk. Mice drinking raw milk had highest serum MMCP-1 and specific-OVA IgE responses. Cultured splenocytes from OVA-primed mice produced similar levels of IL-4 in response to the antigen; however, IL-10 levels were highest from mice drinking raw milk. Overall, the present study adds to the evidence that consuming different types of milk can affect allergic responses to a non-related dietary antigen.

Topics: Alum Compounds; Animals; Cattle; Chymases; Cytokines; Female; Food Handling; Gastrointestinal Tract; Hot Temperature; Immunoglobulin E; Immunoglobulin G; Mice; Mice, Inbred BALB C; Milk; Milk Hypersensitivity; Milk Proteins; Ovalbumin; Spleen; Sterilization

Infants' immunological responses to cow's milk (CM) proteins, which in 2-3% result in allergy, may partially depend on genetic factors. We evaluated whether genes with immunological functions, i.e. human leukocyte antigen (HLA) II, the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) and filaggrin, modulate immune responses to dietary antigens.. We analyzed 14 HLA class II haplotypes, the PTPN22 1858 SNP (R620W allele) and 5 known filaggrin null mutations from blood samples of 87 patients with CM allergy (CMA) and 76 control subjects (age 8.0-9.3 years). Serum levels of IgA, IgG, IgG1 and IgG4 antibodies to beta-lactoglobulin, alpha-casein and ovalbumin were measured with enzyme-linked immunosorbent assay, levels of IgE antibodies to CM, ovalbumin and birch with UniCap (Phadia, Uppsala, Sweden).. In children with CMA, the HLA (DR15)-DQB1*0602 haplotype was associated with high levels of beta-lactoglobulin-specific total IgG (p < 0.001) and IgG4 (p < 0.001) and alpha-casein-specific total IgG (p = 0.003) and IgG4 (p = 0.002), but not among control subjects. (DR1/10)-DQB1*0501 was associated with lower levels of beta-lactoglobulin-specific total IgG (p < 0.001) and IgG4 (p < 0.001), ovalbumin-specific total IgG (p = 0.002) and IgG4 (p < 0.001), particularly in control subjects (p < 0.001). Six children with eczema (3 with CMA) had the filaggrin mutation del22824. PTPN22 was not associated with specific antibody responses or CMA.. The HLA II, but not PTPN22 or filaggrin, genotype modulates humoral responses to early food allergens, whereas none of these genes was associated with CMA.

Topics: Animals; Betula; Caseins; Cattle; Chickens; Child; Dermatitis, Atopic; Filaggrin Proteins; Finland; Haplotypes; HLA-DQ Antigens; HLA-DQ beta-Chains; Humans; Immunity, Humoral; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Intermediate Filament Proteins; Lactoglobulins; Milk Hypersensitivity; Milk Proteins; Ovalbumin; Pollen; Polymorphism, Genetic; Protein Tyrosine Phosphatase, Non-Receptor Type 22

Children with eczema and sensitization to foods are recommended skin care and, if food allergy is proven by challenge, an elimination diet. For most children the diet period is transient, but the process behind tolerance development and the influence of decreased allergen exposure is not fully known. The aim of the study was to investigate the effect of elimination diet on serum and salivary antibodies and to identify immunological parameters related to the ability to tolerate foods. Eighty-nine children, below 2 yr of age, with eczema and suspected food allergy were included. Recommended treatment was skin care to all children, and 60 children had a period of elimination diet. At 4(1/2) yr of age, the children were divided into two groups, based on if they had been able to introduce the eliminated foods, or not. Serum and salivary antibodies were analyzed with enzyme-linked immunosorbent assay and UniCAP before and after a 6-wk treatment period and at 4(1/2) yr of age. Children sensitized to egg and/or milk that could eat and drink the offending foods at 4(1/2) yr of age, had higher levels of Immunoglobulin G(4) antibodies to ovalbumin and beta-lactoglobulin and also higher IgG(4)/Immunoglobulin E ratios on inclusion in the study, than those who had to eliminate egg and/or milk from their diet, beyond 4(1/2) yr of age. The highest IgG(4)/IgE ratios were found in children with circulating IgE antibodies to egg and/or milk but negative skin prick test on inclusion. The 6-wk treatment period did not significantly affect the levels of serum and salivary antibodies. In conclusion, eczematous, food sensitized infants with high levels of IgG(4) and high ratios of IgG(4)/IgE antibodies to food allergens are more likely to consume these foods at 4(1/2) yr than infants with low levels and ratios.

Topics: Allergens; Animals; Child; Child, Preschool; Cohort Studies; Diet; Eczema; Egg Hypersensitivity; Eggs; Humans; Immune Tolerance; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Infant; Lactoglobulins; Milk; Milk Hypersensitivity; Ovalbumin; Prospective Studies; Saliva; Skin Tests

Glycomacropeptide (GMP), arising from the cleavage of kappa-casein by chymosin or pepsin, has been correlated with a wide variety of biological activities including immunosuppression capacity, inhibition of pathogen invasion, and induction of satiety. Due to the interest in exploiting such potential of GMP, we aimed at characterizing the immunogenic properties of GMP as an indication of its potential allergenicity. Immunogenicity of kappa-casein and GMP were investigated using 2 animal models based on different routes of immunization: 1) mice immunized intraperitoneally or subcutaneously with either kappa-casein, polymerized GMP, GMP coupled to the immunogenic carrier ovalbumin, or GMP alone; 2) mice coadministered kappa-casein or GMP and cholera toxin. The specific antibody response to GMP was evaluated as well as the antigen-specific T-cell response. The results demonstrated that immunization or feeding with kappa-casein induced GMP-specific antibodies, whereas GMP per se lacked immunogenicity independently of the mode of presentation. The size of the presented form of GMP did not influence its immunogenicity. Because the results showed that GMP did not induce a specific T-cell response, we postulate that GMP lacks the ability to stimulate antigen-specific T cells.

Topics: Animals; Antibodies; Antigens; Caseins; Electrophoresis, Polyacrylamide Gel; Female; Glycopeptides; Immunization; Immunoblotting; Immunoglobulin G; Immunoglobulin M; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Milk Hypersensitivity; Ovalbumin; Polymers; Spleen; T-Lymphocytes

Topics: Adult; Double-Blind Method; Eosinophils; Female; Food Hypersensitivity; Histamine Release; Humans; Kinetics; Male; Mast Cells; Methylhistamines; Milk Hypersensitivity; Nuts; Ovalbumin; Proteins; Radioallergosorbent Test; Radioimmunoassay; Skin Tests

No adequate enteral sensitization models are available to study food allergy and the allergenicity of food proteins. To further validate an enteral brown Norway (BN) rat sensitization model under development, we studied specific protein recognition to determine whether a comparable pattern of proteins is recognized by the rat immune system and the human immune system.. The animals were exposed to either ovalbumin as a positive reference control, hen's egg-white-protein extract, or a cow's milk preparation by daily gavage dosing (0.5, 1, 2.5, 5, 10, or 15 mg protein per rat/day) for 9 weeks. No adjuvants were used during the sensitization studies. The specificities of antibodies against hen's egg-white proteins or cow's-milk proteins in sera from orally sensitized rats and food-allergic patients were studied and compared by immunoblotting.. The IgG and IgE antibodies to hen's egg-white proteins and cow's-milk proteins present in sera from orally sensitized rats and food-allergic patients showed a comparable pattern of protein recognition.. Upon daily intragastric exposure to food allergens, the specificities of the induced antibody responses in the BN rat resemble those found in food-allergic patients. These studies add further support to the hypothesis that the BN rat may provide a suitable animal model for food allergy research and research on the allergenicity of food proteins.

Topics: Allergens; Animals; Antibody Specificity; Blotting, Western; Child; Child, Preschool; Dietary Proteins; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Food Hypersensitivity; Humans; Immune System; Immunoglobulin E; Infant; Male; Milk; Milk Hypersensitivity; Milk Proteins; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred BN

The relationship between the development of allergy during infancy and breast-feeding remains controversial. This controversy may be due to individual variations in the composition of human milk. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is still unknown. IgA antibodies to inhalant allergens have not been previously detected.. Our purpose was to analyze secretory IgA antibody levels to cat, beta-lactoglobulin, and ovalbumin allergens in colostrum and mature milk in relation to maternal allergy.. Colostrum and samples of mature milk were obtained after 1 and 3 months of lactation from 53 nursing mothers (17 allergic and 36 nonallergic mothers) and were analyzed for total secretory IgA levels by ELISA and secretory IgA antibodies to cat, beta-lactoglobulin, and ovalbumin by an enzyme-amplified ELISA. The specificity of the assays was confirmed by inhibition experiments.. Secretory IgA to cat, beta-lactoglobulin, and ovalbumin allergens were detected in colostrum as well as mature milk. The levels of secretory IgA to ovalbumin were lower in colostrum from allergic mothers with P =.016, whereas the levels to beta-lactoglobulin and cat were similar in the 2 groups. IgA antibodies to ovalbumin were detected in 94% of the colostrum samples from allergic and in all samples from nonallergic mothers, in 82% and 96%, respectively at 1 month, and 53% and 65% at 3 months. Fewer samples had detectable secretory IgA antibodies to beta-lactoglobulin than to ovalbumin and cat, and only 33% and 10% of the samples from the allergic and nonallergic mothers, respectively, remained positive at 3 months. All the allergic mothers had detectable IgA to cat in colostrum, whereas 83% and 73% of the samples were positive at 1 and 3 months. The corresponding numbers were 93%, 81%, and 81% in the nonallergic mothers (not significant).. Even a low level of exposure of the mucosa (eg, by inhalant allergens) can induce antibody secretion into the milk, both in allergic and nonallergic mothers.

Topics: Allergens; Animals; Antibodies; Breast Feeding; Cats; Humans; Immunoglobulin A, Secretory; Lactoglobulins; Milk Hypersensitivity; Mothers; Ovalbumin; Prospective Studies

To investigate the effect of acute watery diarrhoea in children upon humoral immune responses to food antigens and the subsequent development of food allergy.. Serum antibodies to cows' milk, beta-lactoglobulin, alpha-lactalbumin, bovine serum albumin and ovalbumin were measured in 30 children with acute diarrhoea in the acute phase and 1 month after recovery. The children were followed for 1 year to assess the development of food allergy.. IgG antibeta-lactoglobulin titres for the study group increased 1 month after recovery compared to the titres during the acute phase (P = 0.02). Antibody concentration for the other antigens studied did not rise. Four children developed positive IgE antibodies to one or more of the allergens after the diarrhoeal episode, although the titres were very low. None showed evidence of allergy to cows' milk or egg during the year-long follow-up.. Acute diarrhoea in children resulted in increased production of IgG antibody to beta-lactoglobulin and had a priming effect for development of positive IgE antibody to cows' milk. Clinical food allergy was not observed in any of the children during the year-long follow-up.

Topics: Animals; Antigens; Cattle; Child, Preschool; Diarrhea, Infantile; Female; Follow-Up Studies; Humans; Infant; Lactalbumin; Lactoglobulins; Male; Milk; Milk Hypersensitivity; Ovalbumin; Risk Factors; Rotavirus Infections; Serum Albumin, Bovine

The role of food-specific antibodies in the pathogenesis of food allergy is controversial. The first step in solving this controversy may be the assessment of antibody response to food antigens in the normal population. Most of the existing data in this field come from studies that used assays of different standards. This study investigated food-specific antibodies in the normal population using standardized assays. Normal levels of antibody titers were also derived for use as reference. Two hundred and eight individuals from different age groups participated. Immunoglobulin G (IgG) antibodies to cow's milk and its component proteins, and to hen's egg ovalbumin, IgA and IgM antibodies to beta-lactoglobulin and ovalbumin were measured by enzyme-linked immunosorbent assay. The sepharose-radioallergosorbent test was used to measure IgE antibodies to cow's milk and ovalbumin. Titers of IgG antibodies to cow's milk and its component proteins revealed an age-related trend, peaking in the 5 months-1 year age group and then decreased to negligible values in adults. A similar trend was observed with IgG anti-ovalbumin antibodies. Temporal association was less evident for antibodies of other classes. Only six subjects had positive IgE antibodies to cow's milk, while none had positive IgE anti-ovalbumin antibody. The prevalences of IgG antibodies to cow's milk, its component proteins, and ovalbumin are influenced by age and feeding habits. Cross-reactivity to related food antigens is common. The presence of IgE antibodies to food antigens is not a physiological phenomenon.

Topics: Animals; Antibodies; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Food Hypersensitivity; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infant; Infant, Newborn; Lactoglobulins; Male; Milk; Milk Hypersensitivity; Ovalbumin; Radioallergosorbent Test

We have studied the T-cell-mediated response to the major allergen of cow's milk, in a group of newborns at risk of developing cow's milk allergy, and in a control group. Before any atopic status has developed, we observe beta-lactoglobulin-specific primary proliferation only in the group at risk for food-related allergies. In this group, the capability to proliferate is not due to placental transmission of 'factors' from allergic mothers. The recognition of the tested beta-lactoglobulin peptides does not show major differences between the responder and nonresponder populations. In the responder population, the response to p145-161 appears linked to a primary response to ovalbumin, another frequent food allergen. On the basis of our findings, we propose a model in which development of allergic diseases is linked to an alteration of T-cell activation through the engagement by the antigen; the HLA phenotype determines the allergen(s) involved, and other genetic or environmental factors dictate the clinical characteristics of the disease.

Topics: Epitopes; Fetal Blood; HLA-DR Antigens; Humans; Infant, Newborn; Interleukin-4; Lactoglobulins; Lymphocyte Activation; Milk Hypersensitivity; Ovalbumin; Risk Factors; T-Lymphocytes

The study was made of aflatoxin B1 effect on guinea pig alimentary anaphylaxis to chicken ovalbumin (CO) and pasteurized cow milk (PCM), of CO-specific IgG antibody levels, some serum indices, sensitivity of the animals to LD50 histamine. In response to aflatoxin B1 alimentary anaphylaxis both to CO and PCM became more severe, lethality of the anaphylaxis to CO being in logarithmic relation to aflatoxin B1 dose (p < 0.05); specific IgG-antibodies to CO grew in number; serum total protein increased against unchanged levels of albumins; the activity of gamma-glutamyltransferase inhibited; histamine shock gained severity, its lethality being logarithmically related to the aflatoxin B1 dose. The discussion covers mechanisms underlying the animal allergic reactivity responses to aflatoxin B1.

Topics: Aflatoxin B1; Anaphylaxis; Animals; Blood Proteins; Chickens; Dietary Proteins; Drug Interactions; Food Hypersensitivity; gamma-Glutamyltransferase; Guinea Pigs; Immunoglobulin G; Lethal Dose 50; Male; Milk Hypersensitivity; Milk Proteins; Ovalbumin

We have investigated the potential of the inbred Brown Norway (BN) rat as a model for food allergy using two different antigens, ovalbumin (OA) and semi-skimmed milk (SSM). The use of milk-free diet prior to and during exposure to SSM was a key factor in the induction of sensitisation to milk proteins. Investigation of dose received and timing of administration identified a sensitisation regimen using 500 micrograms SSM injected i.p. together with 1 mg CGN (adjuvant) on days 0 and 7 as the optimum conditions for induction of reaginic antibody production. In this model milk proteins were less allergenic than OA as the amount of SSM required to induce sensitivity was 20-fold greater. Examination of antigen-specificity of the IgG and reaginic antibody responses to a range of proteins, present in SSM, showed that the BN rats were capable of recognising a similar profile of allergens as those recognised by milk sensitive humans. Lactoferrin which is present in low concentrations in milk proved as allergenic as the major proteins in milk, the caseins and beta-lactoglobulin. These studies have identified conditions for induction of sensitisation to milk proteins, and have shown the antibody specificity of the response to be similar to that in man. This suggests that the BN rat could provide the basis of a model for the investigation of allergic reactions to food.

Topics: Animals; Antibody Specificity; Disease Models, Animal; Dose-Response Relationship, Immunologic; Immune Sera; Immunoglobulin G; Intradermal Tests; Male; Milk Hypersensitivity; Milk Proteins; Ovalbumin; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; Reagins

The role of T lymphocytes was assessed in patients with food-sensitive atopic dermatitis (AD). T lymphocytes plus monocytes responded well to ovalbumin or bovine serum albumin (BSA) in children with AD who were sensitive to hen's egg or cow's milk compared with healthy children and children with immediate allergic symptoms who are sensitive to hen's egg or cow's milk. The responding cells were shown to be predominantly CD4+ T lymphocytes. Interleukin-2 activity and interferon-gamma concentrations in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells (PBMCs) from patients with AD who were sensitive to hen's egg were significantly higher than those of healthy children and patients sensitive to hen's egg with immediate symptoms. Expression of Fc epsilon R II on B lymphocytes in cultures of ovalbumin-stimulated PBMCs from patients with AD was significantly higher than that of healthy children, but it tended to be lower than that of patients with immediate symptoms. These results suggest that, in patients with AD who are food sensitive, CD4+ T lymphocytes stimulated by food antigens secrete lymphokines such as interleukin-2 and interferon-gamma that are secreted from TH1 clones in mice, and express Fc epsilon R II on B lymphocyte that is induced by interleukin-4 secreted from TH2 clones in mice. Taken together, cell-mediated immunity may also occur in addition to IgE-mediated hypersensitivity in patients with food-sensitive AD.

Topics: Antigens; Cell Division; Cells, Cultured; Child; Child, Preschool; Dermatitis, Atopic; Food Hypersensitivity; Humans; Infant; Interferon-gamma; Interleukin-2; Milk Hypersensitivity; Monocytes; Ovalbumin; Radioallergosorbent Test; Receptors, Fc; T-Lymphocytes

Prospectively, serum levels of IgE, specific IgE antibodies (AB) to whole cow milk protein (CMP), bovine se-albumin, bovine immunoglobulin, bovine lactoferrin, bovine lactalbumin and beta-lactoglobulin (BLG), IgG and IgG subclass antibodies to ovalbumin (OA) and BLG, and IgG4 RAST to CMP (bovine whey) were measured in 39 infants with cow milk protein allergy (CMPA) at birth (cord blood), at time of diagnosis and before and after milk challenge at the age of 12 months. Immunological measurements were also undertaken in 33 control infants without CMPA at birth, at 6 months and at 18 months. At no time, were differences found between the levels of IgG and IgG subclass AB to OA and BLG in control versus infants with CMPA. In the 39 infants with CMPA no correlation was found between the levels of IgE, IgG and IgG subclass AB in cord blood and subsequent levels of these values, irrespective of the type of CMPA (IgE-mediated (CMA) or non-IgE-mediated (CMI)), and irrespective of whether remission had occurred. In cord blood 25/33 (76%) of the infants with CMPA had specific IgE-AB to one or more of the bovine milk proteins indicating a prenatal intrauterine sensitization to cow milk protein. At 6 months the frequency of specific IgE-AB to bovine milk proteins was significantly (p less than 0.05) higher in infants with CMA versus CMI, and at 12 months total serum-IgE and the increase of these specific IGE-AB and RAST to CMP were significantly higher (p less than 0.05) in infants with persistent CMA. From 6 to 12 months withholding milk resulted in a significant fall in specific IgE-AB to CMP, and IgG, IgG1 and IgG4 anti-BLG followed by an increase after milk challenge. Decreasing levels of IgG anti-OA from birth to 6 months reflect passive maternal transfer of IgG through the placenta, and increasing levels of IgG anti-BLG, already from birth to 6 months, may represent an early exposure to CMP in all infants. Significantly higher levels (p less than 0.05) of IgG anti-OA AB, IgG1 and IgG4 anti-BLG AB were found in infants with persistent CMA, indicating a close relation between the synthesis of IgE and IgG and between IgE and IgG subclasses (IgG1 and IgG4) in symptomatic cow milk-allergic individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Child, Preschool; Cohort Studies; Denmark; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Immunoglobulin E; Immunoglobulin G; Incidence; Infant; Lactoglobulins; Male; Milk Hypersensitivity; Milk Proteins; Ovalbumin; Prospective Studies

Animal models of allergic gastroenteropathy have defined both morphologic and physiologic changes that accompany the immune-mediated reaction to a dietary protein. In such models a broadening of the allergic response to other dietary proteins present in the gastrointestinal tract may occur during the localized anaphylactic reaction. The characteristic histologic intestinal findings of food protein-induced enteropathy may develop in selected infants with protracted diarrhea after infectious enteritis. Mechanisms underlying the induction of this response remain to be explained, but they may in part be similar to the broadening of the hypersensitivity response seen in experimental models of allergic enteropathy.

Topics: Acute Disease; Anaphylaxis; Animals; Gastroenteritis; Intestinal Mucosa; Mice; Milk Hypersensitivity; Ovalbumin; Stomach