Antibodies IgG, IgA, and IgM to food antigens during the first 18 months of life in relation to feeding and development of atopic disease

Serum levels of IgG, IgA, and IgM antibodies against ovalbumin, beta-lactoglobulin, and gliadin were measured in a series of 210 "allergy-risk" infants and their mothers. The antibody levels were determined with ELISA in sera obtained from mothers at delivery, and from their babies at birth, 6 weeks, 6 months, and 18 months. High levels of maternal IgG, IgA, or IgM antibodies to food at delivery did not appear to protect the baby against development of atopic disease. Maternal avoidance of cow's milk and egg during pregnancy had no significant influence on the level of food antibodies in cord blood, but the mother's intake of these foods during lactation affected the immunologic response of the baby, not only to these antigens but also to gliadin as well. Babies with minimal cow's milk exposure before 6 months had significantly lower levels of IgG to beta-lactoglobulin than babies regularly exposed to cow's milk. We conclude that maternal elimination diet during lactation influences the immunologic response of the baby, but if this prevents the development of atopic disease or just delays the immunologic maturation remains to be evaluated.     

Total IgE, specific antibodies to cow's milk proteins, beta-lactoglobulin and eczema in one month infants

Total IgE, specific IgE.IgA.IgG.IgM antibodies to whole cow's milk and beta-lactoglobulin were measured in 32 term and 23 premature infants. 1) The term infants who developed eczema till one month had significantly high specific IgG titers to whole cow's milk and beta-lactoglobulin in cord blood serum. It is concluded that specific IgG antibody to whole cow's milk and beta-lactoglobulin in cord blood serum have predictive value for the development of eczema till one month. 2) Some of mixed feeding premature infants produced specific IgE.IgA.IgG.IgM antibodies to whole cow's milk and beta-lactoglobulin till one month. These infants produced various kind of specific antibodies to whole cow's milk and beta-lactoglobulin. 3) The premature infants who developed eczema at one month had significantly high specific IgA.IgG titers to cow's milk and high specific IgA titers to beta-lactoglobulin in serum at one month. These infants had a tendency to show high total IgE value and high specific IgM titers to cow's milk and high specific IgG.IgM titers to beta-lactoglobulin. It is concluded that specific antibodies to whole cow's milk and beta-lactoglobulin are responsible for the development of eczema in one month infants.     

Specific antibodies in infants with gastrointestinal intolerance to cow's milk protein

Antibodies of various immunoglobulin classes against cow's milk proteins were studied in infants and children with cow's milk protein intolerance, gluten-sensitive enteropathy and acute gastroenteritis. Their IgE, IgG, IgM and IgA antibody levels determined with the enzyme-linked immunosorbent assay (ELISA) and the IgE antibodies also determined with RAST, were compared with reference groups of children and adults. IgE, IgT or IgA antibodies against unseparated cow's milk proteins, alpha-lactalbumin, beta-lactoglobulin, alpha-casein and beta-casein were present in many of the studied samples, but did not discriminate between the individuals with and without intolerance symptoms. As a group, the infants with late reactions to cow's milk showed increased levels of IgE and IgG antibodies detected with the ELISA, while patients with gluten-sensitive enteropathy had significantly increased levels of IgG and IgA antibodies of cow's milk proteins compared to the reference group. By combining the findings of antibody increases in various immunoglobulin classes, an individual discrimination could be reached. Thus, 8 of 9 of the patients with late reactions to cow's milk had increased levels of IgE or IgG + IgA antibodies as compared to 3 of 22 in the reference group. Serodiagnosis with the ELISA may, therefore, be of some use in patients with a suspicion of cow's milk protein intolerance.     

Breast milk antibodies to foods in relation to maternal diet, maternal atopy and the development of atopic disease in the baby

Breast milk samples were collected from 152 women during the first week after delivery. The levels of IgG and IgA antibodies to beta-lactoglobulin, ovalbumin and gliadin were assessed with an enzyme-linked immunosorbent assay (ELISA). The breast milk antibody levels did not differ significantly between mothers on a strictly cow's milk and egg-free diet, and mothers taking these foods. Moreover, the colostral food antibody levels did not differ significantly between atopic and non-atopic mothers. Neither was there any correlation between the colostral antibody levels and the development of atopic disease in the baby. I conclude that maternal antigen avoidance during late pregnancy does not affect the food antibody levels in colostrum. High levels of food antibodies in a colostrum sample seem not to offer protection against food allergy in the child.     

Cord blood levels of immunoglobulin G subclass antibodies to food and inhalant allergens in relation to maternal atopy and the development of atopic disease during the first 8 years of life

BACKGROUND: Factors that either protect from or enhance the development of atopic disease appear to be acting early in life. The gestational environment, including maternal immune responses, such as transplacentally transferred immunoglobulin (Ig) G antibodies to allergens, may be of importance in this respect, since allergen-specific immunity has been demonstrated to develop in utero. OBJECTIVE: To evaluate the relation between cord blood IgG subclass antibodies to allergens, maternal atopy and development of atopic disease in the children. MATERIAL AND METHODS: The study group comprised a cohort of 96 children participating in a prospective study up to 8 years of age. Cord blood IgG subclass antibodies to ovalbumin, beta-lactoglobulin, Bet v 1 and cat dander were analysed by ELISA. RESULTS: The levels of all IgG subclass antibodies to ovalbumin and rBet v 1 were higher in newborn infants with an atopic mother, as compared with babies with nonatopic mothers. IgG1 antibody levels to cat and IgG4 antibody levels to beta-lactoglobulin and cat were also higher in atopic than in nonatopic mothers, whereas the other subclass antibody levels to those allergens were similar. High levels of cord blood IgG antibodies to cat and birch, but not to the food allergens, were associated with less atopic symptoms in the children during the first 8 years of life. Moreover, children who developed IgE antibodies to cat had lower levels of IgG antibodies to that allergen at birth. CONCLUSIONS: High levels of cord blood IgG subclass, especially IgG4, antibodies to food and inhalant allergens are associated with maternal atopy. High levels of IgG antibodies to inhalant, but not food, allergens are associated with less development of atopy in the children.     

Maintenance of tolerance to cow''s milk in atopic individuals is characterized by high levels of specific immunoglobulin G4

BACKGROUND: The central role of specific IgE in cow's milk allergy (CMA) is well documented. However, less is known about the function of other immunoglobulin isotypes in allergy and tolerance to cow's milk proteins (CMPs). OBJECTIVE: To determine differences in the antibody responses that are associated with allergy and tolerance to cow's milk in allergic, atopic and non-atopic individuals of different age groups. METHODS: Nineteen infants (<1 year), 18 children (6-14 years) and 41 adults (21-68 years) were included. Each age group was comprised of subjects with CMA, atopic individuals without a history of CMA and non-atopic subjects. Levels of specific IgE, IgG4, IgG1 and IgA to whole cow's milk and the six most abundant individual CMPs were determined in plasma by ELISA. For comparison, specific IgE and IgG4 were measured to ovomucoid and house dust mite (HDM) in individuals allergic for the respective allergens, and in atopic and non-atopic subjects without allergy. RESULTS: In infants and children with CMA, alphas1-casein and beta-lactoglobulin induced the highest specific IgE response, whereas alphas1-casein was the most allergenic CMP in adult patients. Specific IgG4 and IgG1 responses were the highest to alphas1-casein and beta-lactoglobulin in all age groups, while kappa-casein and alpha-lactalbumin induced the highest levels of IgA. CMP-specific IgG4 was higher in atopic children and adults without CMA, as compared with non-atopic individuals. A similar difference between tolerant atopic and non-atopic subjects was observed for IgG4 specific to ovomucoid, whereas HDM-specific IgG4 was not detectable in these subjects. CONCLUSION: Maintenance of tolerance to cow's milk in atopic children and adults without CMA is associated with elevated levels of specific IgG4, in combination with low specific IgE. The up-regulation of specific IgG4 in tolerant atopic individuals may be related to the type of allergen and its regular dose of exposure.     

Immune response patterns in coeliac disease. Serum antibodies to dietary antigens measured by an enzyme linked immunosorbent assay (ELISA)

Serum IgG, IgA and IgM activities to wheat, egg and cow's milk antigens were measured by an ELISA method in children and adults with coeliac disease (CD). In untreated patients, the IgA activity was characteristically raised to gluten antigens but often also to proteins from egg or cow's milk. Setting the upper reference range for gluten antibodies as the highest IgA reading obtained in healthy controls and patients with other intestinal disorders, IgA measurements afforded virtually 100% diagnostic sensitivity and specificity and detected 94% of children and 80% of adults with untreated CD. Such measurements, therefore, represent a valuable adjunct in the diagnosis of this disease. IgA activity to beta-lactoglobulin, casein or ovalbumin higher than the normal 95 percentile was found in 44-89% of untreated patients. Reduction of these antibody titres seemed to reflect relatively well the response to treatment with a gluten free diet, particularly the activity to beta-lactoglobulin. Monitoring of IgA antibodies to dietary antigens other than gluten may therefore be of particular importance in the follow-up of CD patients.     

Serum ovalbumin-specific immunoglobulin G responses during pregnancy reflect maternal intake of dietary egg and relate to the development of allergy in early infancy

BACKGROUND: The value of allergen elimination diets during pregnancy for primary prevention of infant allergy has been questioned. However, dietary compliance may influence effectiveness. OBJECTIVES: To monitor egg intake during a randomized controlled trial of egg avoidance throughout pregnancy and lactation by serial measurements of serum ovalbumin (OVA) IgG concentration in conjunction with dietary diary record and also, to analyse specific IgG concentrations at birth in relation to infant allergic outcome. METHODS: Pregnant women, with personal or partner atopy, were randomized to complete dietary egg exclusion or an unmodified healthy diet before 20 weeks gestation. The infants were evaluated for atopy at 6 months of age. Serum food-specific IgG concentrations were determined by ELISA in maternal samples collected at study recruitment and during labour, and in infant samples at birth (umbilical cord). RESULTS: Serum-specific IgG to OVA, but not the unrelated allergen, cow's milk beta-lactoglobulin, decreased over pregnancy in egg-avoiding women only (P<0.001). Cord OVA IgG concentration correlated with maternal IgG at delivery (r=0.944; P<0.001), and for infants born to atopic women, cord concentration was higher than that of their mother's (P<0.001). Infants with the lowest and highest cord IgG concentrations were the least likely, and those with mid-range concentrations were the most likely, to be atopic by 6 months of age (P=0.008). CONCLUSION: Serum OVA IgG concentration reflects egg consumption, thereby indicating dietary allergen doses to which the developing immune system might be exposed. Trans-placental maternal IgG must be considered among early life factors that regulate infant atopic programming.     

Total and allergen-specific immunoglobulin A levels in saliva in relation to the development of allergy in infants up to 2 years of age.

BACKGROUND: The association between salivary IgA levels and development of allergy is controversial and the employed methodology has been questioned. OBJECTIVE: The aim of the study was to relate the levels of total IgA, SIgA and allergen-specific IgA antibodies in saliva to the development of allergy in infants during the first 2 years of life. METHODS: Saliva samples from 80 infants participating in a prospective study regarding the development of allergy were collected at 3 or 6, and 12 and 24 months of age. Total IgA, SIgA and Fel d 1 and beta-lactoglobulin specific IgA levels were analysed with ELISA. RESULTS: The levels of total IgA and SIgA increased with age. The number of samples with detectable IgA to Fel d 1 tended to increase with age, whereas the opposite was observed for IgA to beta-lactoglobulin. Infants who developed allergy tended to have higher levels of total IgA, and allergen-specific IgA was more commonly detected than in non-allergic children. In contrast, non-allergic children tended to have higher levels of SIgA. Furthermore, the levels of SIgA were higher in sensitized infants with no allergic symptoms than in sensitized children with symptoms. Infants with allergic parents had lower SIgA levels than infants without. Direct exposure to cat and cow's milk did not influence the levels of allergen-specific IgA levels, nor was there any association between breast-feeding and IgA production. CONCLUSION: The kinetics of food and inhalant allergen-specific IgA in saliva during the first 2 years of life is similar to what has earlier been shown for IgG in serum. Development of allergy tended to be associated with high levels of total and allergen-specific IgA antibodies, but low levels of SIgA. Furthermore, high levels of SIgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life, supporting a possible protective role of SIgA against development of allergy.     

Avidity progression of dietary antibodies in healthy and coeliac children

In most individuals minute amounts of food proteins pass undegraded across the intestinal mucosa and trigger antibody formation. Children with coeliac disease have enhanced antibody production against gliadin as well as other dietary antigens, e.g. beta-lactoglobulin, in cow's milk. Antibody avidity, i.e. the binding strength between antibody and antigen, often increases during antibody responses and may be related to the biological effectiveness of antibodies. The aim of the present study was to determine the avidity of serum IgG antibodies against beta-lactoglobulin and gliadin in healthy children during early childhood and compare these avidities to those found in children with coeliac disease. The average antibody avidity was analysed using a thiocyanate elution assay, whereas the antibody activity of the corresponding sera was assayed by ELISA. The avidity of serum IgG antibodies against beta-lactoglobulin as well as gliadin increased with age in healthy children, even in the face of falling antibody titres to the same antigens. Children with untreated coeliac disease had IgG anti-beta-lactoglobulin antibodies of significantly higher avidity than healthy children of the same age, and the same trend was observed for IgG antigliadin antibodies. The present data suggest that the avidities of antibodies against dietary antigens increase progressively during early childhood, and that this process seems to be accelerated during active coeliac disease.     

Immunogenicity and antigenicity of a partially hydrolyzed cow's milk infant formula

We evaluated the immunogenicity and antigenicity of a formula based on partially hydrolyzed cow's milk whey protein in infants at risk of atopy and in controls. Total IgE and specific IgE, IgG, and IgG4 subclass antibodies against egg albumin and cow's milk α-lactalbumin, casein, and β-lactoglobulin were measured by radioimmunoassay of cord blood and of peripheral blood at 5 days and 6 months of life in five groups of infants: 16 breast-fed infants at risk of atopy (group 1), 21 partially hydrolyzed whey formula-fed infants at risk of atopy (group 2), 14 formula-fed infants at risk of atopy (group 3), 10 breast-fed control infants (group 4), and 13 formula-fed control infants (group 5). Total IgE concentration was significantly lower in group 2 at 6 months than in groups 3 and 5 infants and similar to that observed in groups 1 and 4 infants. The concentration of specific antiegg and anti-cow's milk protein IgG and of specific anti-cow's milk α-lactalbumin and β-lactoglobulin IgG4 subclass antibodies was significantly reduced in group 2 as compared to group 3 infants and similar to that found in breastfed infants. In conclusion, the partially hydrolyzed formula was less immunogenic and antigenic than a traditional formula and was as immunogenic and antigenic as breast milk.     

Ontogeny of the antibody response to cow milk proteins

Twenty-nine infants were followed prospectively for the development of immunoglobulin G (IgG) and IgE antibodies to the cow milk proteins (CMPs) alpha-lactalbumin, alpha-casein, and beta-lactoglobulin. Thirteen infants were fed formula, eight were exclusively breast fed, and eight were breast fed with formula supplementation. By 4 months of life, infants fed formula or breast milk with formula supplementation had elevated IgE and IgG antibody levels to CMPs, when compared with values before 1 month of age. Further, breast-fed infants demonstrated significantly lower levels of IgE and IgG antibodies to CMPs than infants who received formula or breast milk with formula supplementation. Clinical symptoms of cow milk allergy were more common in infants fed formula or breast fed with supplementation, but were not significantly related to the presence of specific antibody. Our data suggest that the formation of CMP antibodies may reflect a normal humoral response following exposure to CMP antigens in this age group.     

Human serum antibodies reactive with dietary proteins. Antigenic specificity

The antigenic specificity of human serum IgG antibodies reactive with common dietary proteins has been evaluated by competitive binding using a solid-phase immunoassay (ELISA). Antibodies reactive with bovine milk antigens were shown to be reactive predominantly with casein, rather than alpha-lactalbumin, beta-lactoglobulin, gamma-globulin or albumin. Furthermore, sera containing antibodies reactive with bovine casein, wheat gliadin and chicken ovalbumin showed competitive binding only by each respective dietary protein antigen. IgG4 antibodies specifically reactive with ovalbumin, gliadin or casein were also not cross-reactive in competitive binding studies. Furthermore, both IgG2 and IgG4 anti-milk antibodies showed significant inhibition only with bovine casein, and not with alpha-lactalbumin or beta-lactoglobulin. These data are relevant to concepts regarding the immunobiological role of antibodies of the IgG4 isotype.     

Transforming growth factor-beta1 in mothers' colostrum and immune responses to cows' milk proteins in infants with cows' milk allergy.

BACKGROUND: Breast milk contains immune factors that compensate for the underdeveloped defenses of the gut of the newborn infant. OBJECTIVE: We sought to study the importance of these factors in the immune responses of infants with cows' milk allergy (CMA) to the proteins in cows' milk (CM). METHODS: We prospectively followed the development of CMA in 6209 healthy infants and collected samples of colostrum from mothers. Samples from mothers of infants with CMA and from control subjects were analyzed for immunoglobulins, CM-specific antibodies, and cytokines. In infants with CMA, correlations between the concentration of transforming growth factor (TGF)-beta1 in colostrum and the extent of the immune response to CM proteins were studied. RESULTS: The concentration of TGF-beta1 in colostrum samples from mothers of infants with IgE-mediated CMA (n = 65) was lower (mean, 589 pg/mL; 95% confidence interval [CI], 413-840) than from mothers of infants with non-IgE-mediated CMA (n = 37; mean, 1162 pg/mL; 95% CI, 881-1531; t = 2.57, P =.012). In 126 control subjects the mean concentration was 807 pg/mL (95% CI, 677-963). In the infants with CMA (n = 96-100), the concentration of TGF-beta1 in colostrum was positively correlated with IgA antibodies to beta-lactoglobulin and IgG antibodies to alpha-casein and whole formula and negatively with the diameter of a skin prick test response to CM and lymphocyte stimulation indices to alpha-casein and beta-lactoglobulin. CONCLUSIONS: In an infant prone to having CMA, the TGF-beta1 content of mother's colostrum may promote IgG-IgA antibody production and inhibit IgE- and cell-mediated reactions to CM.     

Effect of cow's milk protein absorption on the anaphylactic and systemic immune responses of young rabbits during bacterial diarrhoea.

In vivo and in vitro studies recently showed that intestinal permeability to cow's milk proteins such as beta-lactoglobulin increased transiently in infant rabbits infected by the enteroadherent Escherichia coli strain RDEC-1 at weaning. The consequences of this enhanced permeability for local anaphylactic and/or systemic immune responses were studied in infected and age-matched control rabbits at weaning, given either water or cow's milk diluted in water in addition to their solid diet. The systemic immune response was determined by measuring IgG, IgA, IgM, and IgE antibodies to cow's milk proteins. A rise in IgG and IgM, but not IgA or IgE, antibody titres to milk protein was observed. Further, infected milk-drinking rabbits had significantly higher beta-lactoglobulin and casein IgG titres than milk-drinking controls. The anaphylactic response was tested by mounting ileal segments in Ussing chambers, adding the milk proteins to the serosal side of the tissue and recording the variation in short-circuit current in order to detect any electrogenic chloride secretion. No change in short-circuit current was observed in the presence of milk proteins in infected or age-matched control milk-drinking rabbits, indicating the absence of any immediate hypersensitivity reaction. These results indicate that at weaning, the rabbit is not prone to developing anaphylactic responses to milk proteins. The rise in milk protein IgG antibodies that followed infection with RDEC-1 might favour the elimination of milk protein-IgG immune complexes from the systemic circulation. The present results emphasize the evidence that genetic background and/or animal species greatly influence the immune response to an antigenic load.     

Cow's milk stimulated lymphocyte proliferation and TNFalpha secretion in hypersensitivity to cow's milk protein

Although there is no reliable single laboratory test available for the diagnosis of cow's milk allergy, if an allergic mechanism is suspected, a number of laboratory studies may be useful in delineating specific proteins responsible for these disorders. In the current study we analyzed in vitro lymphocyte proliferation assays, specific secretion of TNFalpha in supernatant cultures and specific IgE, IgG, and IgA in a group of patients with hypersensitivity to cow's milk antigens. The stimulation index against a cow's milk antigen mixture, alpha-lactalbumin, beta-lactoglobulin, and casein was significant higher in the group of patients maintained on cow's milk-free diet for less than 4 months compared with the values observed in the control group and in the group of patients without a close contact to cow's milk proteins. A significant increase in TNF-alpha secretion was observed in supernatants from patients with close contact to cow's milk (CM). Specific IgE was detected in 59.3% of the patients, with higher specific IgE levels in patients who were not positive for the proliferation assay, suggesting a clear difference in the two mechanisms proposed as effectors in this disease. No differences in specific IgG and IgA levels were observed between the patient group and the control group, with a great dispersion among individuals in all groups tested. We conclude that a combination of the assays tested in this study, such as proliferative assay of peripheral blood mononuclear cells to CM, the quantitation of TNFalpha in culture supernatants, and serum specific IgE determination, are useful laboratory tests to identify cow's milk allergy among patients with immediate and non immediate adverse reactions, reducing the need for food allergen challenges in young children.     

Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross-sectional study

BACKGROUND: Because IgG antibodies to foods can be detected before IgE antibodies to inhalants, increased levels of IgG antibodies to foods might be used as a predictor of IgE-mediated allergy in initially nonatopic children. OBJECTIVE: To examine the cross-sectional relation between IgG to foods (i.e. mixture of wheat and rice, mixture of soybean and peanut, egg white, cow's milk, meat, orange and potato) and specific IgE to cat, dog, mite, milk and egg white in 1-year-old children. METHODS: All atopic children (n = 120; 58 with and 62 without eczema) and a random sample of the nonatopic children (n = 144) of the Bokaal study were tested on their IgG response to foods. The IgG results of the food assays were dichotomized high or low using the 66th centile as a cut-off value. RESULTS: Atopic children more often had high IgG levels to foods than nonatopic children. IgG to egg white (OR = 7.50) and mixture of wheat and rice (OR = 4.79) were most strongly associated with positive specific IgE. In a stepwise logistic regression analysis egg white, mixture of wheat and rice, and orange were selected (OR = 3.76, OR = 2.43, and OR = 2.11, respectively). In children without eczema higher levels of IgG to foods were still significantly associated with atopy, which was most prominent for egg white, orange and cow's milk. CONCLUSION: An increased IgG antibody level to foods, especially to egg white, orange, and mixture of wheat and rice, indicates an increased risk of having IgE to cat, dog, mite, egg and/or milk allergens, even in the noneczematous group. Therefore, in another prospective study we are currently investigating the usefulness of IgG in early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing allergic diseases in the future.     

Cow's milk-specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula

BACKGROUND: Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast-feeding is not possible. We studied the specific cellular and humoral immune response to cow's milk proteins and occurrence of atopic dermatitis under different feeding regimens: two hydrolyzed infant milk formulas (partially [pHF] and extensively hydrolyzed [eHF]) and under exclusive breast-feeding (BF). METHODS: Seventy-two infants from families with atopic symptoms were randomized in the pHF and eHF groups, respectively. At 6 and 12 months of age, peripheral blood mononuclear cell proliferation along with specific IgG and IgE to cow's milk proteins was determined in infants fed pHF or eHF, respectively, and those who had not yet received any formula at 6 months of age (BF). Cases of atopic dermatitis were recorded throughout the first 12 months of life, and their severity was evaluated with SCORAD points. RESULTS: A significantly decreased proliferation to cow's milk caseins was found in the pHF group compared to the exclusively breast-fed group. Medians of stimulation indexes for CAS at 6 months were as follows: pHF 1.18; n=24; BF 1.70; n=24 (P=0.033, Mann-Whitney U-test). Higher levels of plasma IgG antibodies to BCAS were found in infants fed pHF than in those fed eHF at 12 months. Optical density (OD): (25th percentile; median; 75th percentile): pHF: 0.00; 0.14; 0.38; n=30; eHF: 0.00; 0.03; 0.14; n=28; P=0,089, Mann-Whitney U-test. Cow's milk-specific IgE was detected at 6 months as follows: BF: 3 of 24; eHF: 2 of 21; pHF: 0 of 23. The number of cases of atopic dermatitis and their severity did not differ among the groups during the first 12 months. CONCLUSIONS: Feeding pHF appears to suppress cow's milk-specific cellular responses and stimulate specific IgG production. Specific IgE sensitization can occur also with breast-feeding.     

Antibody-dependent cell-mediated cytotoxicity to beta-lactoglobulin-coated cells with sera from children with intolerance of cow''s milk protein.

The capacity of serum antibodies against beta-lactoglobulin to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) was analysed in sera from children with cow's milk protein intolerance (CMPI). The children with CMPI were divided into three groups according to clinical features: delayed-onset CMPI with gastrointestinal symptoms (n = 8); immediate-onset CMPI with gastrointestinal and skin symptoms (n = 8); and immediate-onset CMPI with skin symptoms only (n = 8). The CMPI groups were compared with children with untreated (n = 9) or treated (n = 8) coeliac disease and a control group (n = 22). Sera from the children were examined for cytotoxic effects using lymphocytes from healthy adults as effector cells and radiolabelled beta-lactoglobulin-coated erythrocytes from the same donor as target cells. In addition, IgG and IgA serum antibodies against beta-lactoglobulin were determined with ELISA. Sera from children with CMPI and gastrointestinal symptomatology showed a significantly increased capacity to induce ADCC reactivity as compared with controls. This increased capacity was seen in sera from those with immediate as well as delayed onset of the gastrointestinal symptoms. In contrast, sera from children who had an immediate-onset CMPI with only skin symptoms mediated no such increase in ADCC reactivity. Moreover, children with coeliac disease with a few exceptions, demonstrated low ADCC reactivity, despite the fact that they had high levels of antibodies against beta-lactoglobulin. ADCC may be an immunopathogenic mechanism in certain cases of CMPI with gastrointestinal symptoms.     

Effect of maternal diet during lactation on development of bovine insulin-binding antibodies in children at risk for allergy

BACKGROUND: The role of exposure to dietary antigens through maternal milk is intriguing, because it may result either in immunization or in tolerance. Exposure to cow's milk proteins results in antibody formation against bovine insulin in infants at risk for type 1 diabetes. OBJECTIVE: To study the appearance of IgG antibodies to bovine and human insulin in infants with an atopic family history whose mothers followed a cow's milk-free diet during the first 3 months of lactation. METHODS: In a prospective cohort study on prevention of food allergies, 123 infants were exclusively breast-fed or received supplementation with a hydrolyzed casein-based formula (Nutramigen) until the age of 6 months. The mothers either avoided cow's milk during the first 3 months of lactation (diet group) or had an unrestricted diet (nondiet group). The levels of IgG antibodies to bovine and human insulin were determined by enzyme immunoassay at 3, 6, 12, and 18 months and at 4 years. In addition, cord blood was obtained at birth and a maternal sample at delivery. RESULTS: At 3 months, IgG antibodies to bovine insulin were low in both dietary groups (median levels 0.150 and 0. 114 optical density units in the diet and nondiet groups). After exposure to dietary insulin, IgG antibodies to bovine insulin increased in both groups, reaching a peak at 12 months in the nondiet group and at 18 months in the diet group. At 18 months, IgG antibodies to bovine insulin were lower in infants in the nondiet group than in infants in the diet group (0.287 vs 0.500, P<.0001). At 4 years, the antibodies no longer differed between the groups. CONCLUSION: The exposure to cow's milk proteins through breast milk during the first 3 months of life resulted in decreased levels of antibodies to dietary bovine insulin at 18 months of age, suggesting a role for breast milk antigens in early tolerance induction.