Cow's Milk Antibodies Research Articles

Avoidance of Cow's Milk–Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial

Feeding during the first months of life might affect risk for celiac disease. Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow's milk proteins. Avoidance of cow's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies. We performed a randomized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease. We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes. The infants were randomly assigned to groups fed a casein hydrolysate formula (n= 113) or a conventional formula (control, n= 117) whenever breast milk was not available during the first 6-8 months of life. Serum samples were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase (anti-TG2A) using a radiobinding assay, to endomysium using an immunofluorescence assay, and antibodies to a deamidated gliadine peptide using an immunofluorometry assay. Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units. Cow's milk antibodies were measured during the first 2 years of life. Of the 189 participants analyzed for anti-TG2A, 25 (13.2%) tested positive. Of the 230 study participants observed, 10 (4.3%) were diagnosed with celiac disease. We did not find any significant differences at the cumulative incidence of anti-TG2A positivity (hazard ratio, 1.14; 95% confidence interval, 0.51-2.54) or celiac disease (hazard ratio, 4.13; 95% confidence interval, 0.81-21.02) between the casein hydrolysate and cow's milk groups. Children who developed celiac disease had increased titers of cow's milk antibodies before the appearance of anti-TG2A or celiac disease. In a randomized controlled trial of 230 infants with genetic risk factors for celiac disease, we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with cow's milk-based formula would decrease the risk for celiac disease later in life. Increased titers of cow's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life. ClinicalTrials.gov Number: NCT00570102.

The role of specific IgE antibodies in infants with cow milk protein allergy

Objectives This article aims to evaluate the role of lactoglobulin-specific IgE and lactalbumin-specific IgE in cow milk allergy. Background Allergy to cow milk is the most common food allergy in infants and young children. Symptoms of milk allergy reaction can range from mild symptoms such as hives, to severe symptoms, such as anaphylaxis. The allergy is most likely to persist in children who have high levels of cow milk antibodies in their blood. The aim of this study is to assess the value of lactalbumin-specific IgE and lactoglobulin-specific IgE in the diagnosis of cow milk protein allergy. Participants and methods This study was carried out on 70 participants classified into the following groups: group 1: it included 50 infants with suspected cow milk protein allergy, who were diagnosed with chronic diarrhea with a history of recent introduction of cow milk and a positive elimination test. Group 2: it included 20 age-matched and sex-matched apparently healthy participants. Their ages ranged between 8 and 18 months. All individuals included in this study were subjected to full history taking, clinical examination, complete blood count, and determination of serum total IgE, lactoglobulin-specific and lactalbumin-specific IgE which was carried out using the enzyme-linked immunosorbent assay technique. Results The diagnostic accuracy of lactoglobulin IgE in the diagnosis of cow milk protein allergy was 84%, with sensitivity of 78%, specificity of 100%, positive predictive value of 100%, and a negative predictive value of 65% at the cutoff point of 0.345 IU/ml. The diagnostic accuracy of lactoalbumin IgE in the diagnosis of cow milk protein allergy was 83%, with sensitivity of 84%, specificity of 80%, positive predictive value of 91%, and negative predictive value of 67% at the cutoff point of 0.335 IU/ml. Conclusion Lactalbumin-specific and lactoglobulin-specific IgE assays are important in the diagnosis of cow milk protein allergy and their combination may give better diagnostic accuracy than the total IgE assay.

Utility of Basophil Activation Test for monitoring the acquisition of clinical tolerance after oral desensitization to cow's milk: Pilot study.

The quantification of basophil activation by flow cytometry is a useful tool for the assessment of immediate-type responses to food allergens and the prediction of clinical tolerance in food allergy patients. The aim of this study is to investigate how the analysis of allergen-induced CD63 up-regulation by flow cytometry can be effective in monitoring the acquisition of clinical tolerance by specific oral desensitization in food allergy. To our knowledge, this is the first study to examine this topic. Three male patients affected by cow's milk allergy underwent successful oral desensitization to cow's milk. In order to monitor the acquired clinical tolerance that occurred after treatment, we performed laboratory tests for total and specific IgE, specific IgG4 and the Basophil Activation Test (BAT) both at baseline and at the end of the desensitization protocol. Using a fluorescent enzyme immunoassay, the comparison of specific cow's milk antibodies before and after treatment showed a decrease of specific IgE levels, without reaching normal values, and an increase of specific IgG4 levels. A complete suppression of cow's milk proteins (α-lactoalbumin, β-lactoglobulin and casein) induced CD63 regulation was observed in all three reported cases. Using flow cytometry, food allergen-specific basophil responses could be monitored in order to identify an acquired tolerance induced by desensitization treatment. Although further studies are needed to develop this important new topic, it was interesting to note that the BAT seemed to be more sensitive and characterized by a close correlation with clinical tolerance.

Surface Plasmon Resonance imaging-based sensing for anti-bovine immunoglobulins detection in human milk and serum

Only few papers deal with Surface Plasmon Resonance imaging (SPRi) direct detection on complex matrices, limiting the biosensor application to real analytical problems. In this work a SPRi biosensor for anti-bovine IgG detection in untreated human bodily fluids, i.e. diluted human serum and milk, was developed. Enhanced levels of cow's milk antibodies in children's serum are suspected for their possible correlation with Type 1 diabetes during childhood and their detection in real samples was up to now performed by classical immunoassays based on indirect detection. The biosensor was optimised in standard samples and then in untreated human milk for anti-bovine IgG direct detection. The key novelty of the work is the evaluation of matrix effect by applying to real samples an experimental and ex ante method previously developed for SPRi signal sampling in standard solutions, called “Data Analyzer”; it punctually visualises and analyses the behaviour of receptor spots of the array, to select only spot areas with the best specific vs. unspecific signal values. In this way, benefits provide by SPRi image analysis are exploited here to quantify and minimise drawbacks due to the matrix effect, allowing to by-pass every matrix pre-treatment except dilution.

1294 Iron Deficiency Anemia in a Child with Idiopathic Pulmonary Hemosiderosis

Background: Idiopathic pulmonary hemosiderosis(IPH) is a rare disease with a variable outcome. Itis characterized by recurrent episodes of diffusealveolar hemorrhage and iron deficiency anemia. Case Report: A 6-year-old boy, was hospitalizedfor severe anemia. At the time of the diagnosis hepresented with progressive fatigue and pallor. Thephysical examination revealed mucocutaneous pallor, a grade III/VI systolic murmur and inspiratorycrackles. Laboratory investigation revealedmicrocytic hypochromic anemia (hemoglobin5.7 g/dL, mean corpuscular volume of 58.9 fL, reticulocyte index 2.18) with iron deficiency, normalrenal and liver function, and normal coagulationprofile. Admitted under iron suplementationwith progressive rise in hemoglobin. Infectiouscauses were excluded. Bone marrow biopsy wasnormal. After 1 month he developed fever, coughand dispnoea, without hemoptysis. The chestradiograph showed diffuse alveolar-type infiltrates. Bronchoscopy with bronchoalveolar lavage reveleadover 75% haemosiderin -stained macrophages. Lung biopsy specimen was negative for vasculitis, immune complex deposition or granulomatousdisease. The immunological study was negative, including anti-GBM, ANA, c-ANCA, IgE cow's milkantibodies and reumatoid factor. Echocardiographyrevealed no evidence of pulmonary hypertension. The diagnosis of IPH was considered and thepatient was started on prednisolone (2 mg/kg/day)with improvement in respiratory symptoms after 1week. Despite corticosteroids he kept having IPHexacerbations and chronic anemia and initiatedhydroxichloroquine with good clinical response. Comments: In this case the association of irondeficiency anemia refractory to iron supplementationwith the sudden onset of respiratory symptoms andthe suggestive radiological presentation establishedthe diagnosis of IPH.

A Japanese infant with localized ichthyosis linearis circumflexa on the palms and soles harbouring a compound heterozygous mutation in the SPINK5 gene

We report a 6-month-old Japanese boy showing ichthyosis linearis circumflexa localized on the palms and soles. He showed bamboo hairs and aminoaciduria, and was positive for cow's milk and egg IgE antibodies by radioallergosorbent tests. Trypsin-like hydrolytic activity in the patient's lesional stratum corneum showed an activity seven times higher than that in age-matched controls. DNA analysis showed that the patient harboured the compound heterozygous mutations R790X and 1220+1 G-->C in the SPINK5 gene, compatible with the diagnosis of Netherton syndrome (NS). As the genotype/phenotype correlations in NS have not yet been fully clarified, the position of the premature termination codon in the SPINK5 gene may contribute to explain such a mild form of NS in our patient.

Maternal consumption of dairy products during pregnancy and lactation, and the development of cow's milk antibodies in the offspring

To assess whether the maternal consumption of milk and milk products affects development of cow's milk (CM) antibodies in infants. A randomized pilot trial using food frequency questionnaires (mothers) and food records (infants). Families with a newborn infant with increased HLA-DQB1-conferred risk of type 1 diabetes and at least one first-degree relative affected by type 1 diabetes from 16 hospitals in Finland between April 1995 and November 1997. Infants randomized to receive a hydrolysed formula when breast milk was not available during their first 6-8 mo (n=112). Of these, 13 dropped out by the age of 3 mo and two were excluded due to incomplete CM antibody data. Maternal milk protein intake from cheese during pregnancy was inversely related to IgA-class antibody titres to beta-lactoglobulin (BLG) and casein (CAS) at 3 mo, and to IgA antibody titres to BLG at 6 mo. Maternal consumption of raw milk products during lactation was positively related to the development of IgA antibody titres to CAS at 6 mo, and inversely correlated to IgG antibody titres to bovine serum albumin (BSA) and IgA antibody titres to CAS at 2 y. Maternal cheese consumption was inversely related to the IgG antibody titres to CM formula and CAS and to the IgA antibody titres to CAS in early infancy. Few associations were established between maternal CM protein intake and CM protein antibody levels in the infants. The milk and milk products taken by the mother differed in their impact on the emerging CM antibody response in the offspring.

Maternal consumption of dairy products during pregnancy and lactation, and the development of cow's milk antibodies in the offspring

Maternal consumption of dairy products during pregnancy and lactation, and the development of cow's milk antibodies in the offspring

IgG and IgA antibody levels to cow's milk are low at age 10 years in children born preterm.

Both innate and specific defenses of the preterm infant are even less developed than those of term infants, and the immune systems of preterm infants might be skewed differently at birth. Their immune responses to food antigens started early in life might therefore differ from those of term infants. We sought to compare antibody levels to cow's milk, ovalbumin, and gliadin at age 10 years in children who had been born either preterm or at term. IgG and IgA isotype antibodies to whole cow's milk, beta-lactoglobulin, alpha-casein, and ovalbumin, as well as IgG antibody levels to gliadin and to tetanus and diphtheria toxoids, were measured for a group of 62 children born preterm and 61 control subjects born at term. These children were studied at the same time for atopy. Children born preterm had markedly lower levels of antibodies to cow's milk and to its protein fractions (P <.0001 for IgA and IgG antibodies to cow's milk and alpha-casein and IgG beta-lactoglobulin antibodies). IgG gliadin antibodies were also significantly lower in the preterm group (P =.03), although the difference was not significant for IgG ovalbumin antibodies. In the preterm group both those born before gestational week 30 and those given cow's milk-based formula early (before day 50) had the lowest levels of cow's milk antibodies. In the preterm group atopy was associated with low levels of IgG cow's milk antibodies but with high levels of IgG ovalbumin antibodies. Early introduction of food antigens into the immature gastrointestinal tract of preterm infants might result in tolerance. The presence of less atopy in these children might also be a result of tolerance development.

Infant feeding patterns affect the subsequent immunological features in cow's milk allergy.

The first exposure to food antigens provokes an immune reaction in an infant, its type depending on the quantity and frequency of doses and the age at introduction, and also being influenced by genetic factors. Most infants develop tolerance to food antigens, but in a small minority they provoke adverse symptoms. To study the effects of breast and formula feeding and other environmental and genetic factors on the subsequent type of cow's milk allergy classified by the presence or absence of immunoglobulin (Ig) E antibodies to cow's milk. A cohort of 6209 infants was followed prospectively from birth for symptoms of cow's milk allergy. The infant-feeding regimen was recorded at the maternity hospital and at home. At a mean age of 6.7 months, a total of 118 infants (1.9%) reacted adversely to a challenge with cow's milk. Before the challenge, the response to a skin-prick test with cow's milk and serum IgE cow's milk antibodies was measured. At challenge, 75 (64%) infants showed IgE-positive reactions to cow's milk, their most common symptom being acute-onset urticaria. Significant risk factors for the presence of IgE cow's milk antibodies in allergic infants were long breast-feeding (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.6-9.8), exposure to cow's milk at the maternity hospital (OR 3.5, 95% CI 1.2-10.1) and breast-feeding during the first 2 months at home either exclusively (OR 5.1, 95% CI 1.6-16.4) or combined with infrequent exposure to small amounts of cow's milk (OR 5.7, 95% CI 1.5-21.6). Fifty infants had their first adverse symptoms during exclusive breast-feeding, and 32 infants were sensitized during exclusive breast-feeding. Most of the infants in both cases were IgE-positive: 37 and 23, respectively. In infants who are prone to developing cow's milk allergy, prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of cow's milk during the first 2 months of life induces development of IgE-mediated response to cow's milk.

Cross-reactivity between milk proteins from different animal species.

Cow's milk allergy is quite frequent in the first years of human life. When breast-feeding is not possible, a cow's milk substitute must be provided for allergic subjects. Different alternatives to cow's milk have been suggested as protein sources (soy, hydrolysed proteins, goat's milk, etc.), but all these dietetic solutions are not without risks for polyallergic or more sensitive subjects. To obtain new information on the suitability of other mammalian milks for allergic children, we evaluated the cross-reactivity between milk proteins from different animal species. Milk samples were analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). To detect antibody-antigen complexes, immunoblotting was performed by using sera from children allergic to cow's and ewe's milk (RAST class >/= 4) and monoclonal antibodies (MoAb) specific for bovine proteins (caseins and beta-lactoglobulin). IgEs from children allergic to cow's milk are capable of recognizing most part of milk proteins from mammals bred in European countries (ewe, goat, buffalo), while no serum used in this study contains IgEs reacting with camel's milk proteins. Camel's milk was also not recognized from circulating IgEs from a child specifically allergic to ewe's milk. Specific antibovine monoclonal antibodies cross-reacted with proteins from other mammalian species, apart from those of camel. Homologies in amino acidic composition could justify the cross-reactivity observed between proteins from different animal species. On the other hand, the phylogenetic difference could be responsible for the failed recognition of camel's proteins by circulating IgEs and monoclonal antibodies.

Relation between antibodies to islet cell antigens, other autoantigens and cow's milk proteins in diabetic children and unaffected siblings at the clinical manifestation of IDDM. The Childhood Diabetes in Finland Study Group.

The relation between islet cell specific antibodies, other autoantibodies and antibodies to cow's milk proteins was studied in IDDM and pre-IDDM by analysing islet cell antibodies (ICA), insulin autoantibodies (IAA), anti-nuclear (ANA), anti-reticulin class IgA [ARA(IgA)], smooth muscle, anti-mitochondria, parietal cell (PCA), adrenal and thyroid antibodies and antibodies to cow's milk formula (CMF), beta-lactoglobulin (BLG) and bovine serum albumin (BSA) in a population based study with more than 650 children with newly diagnosed IDDM and more than 550 initially non-diabetic siblings. After adjustment for age a weak association was seen in the diabetic children between IAA and ANA but none between ICA and autoantibodies directed against the other organ-specific or non-organ-specific antigens. There was no significant difference in cow's milk antibodies between diabetic children with and without ICA or IAA. The siblings with ICA had higher CMF (IgA and IgM) antibody levels and BLG (IgA) antibody levels than the remaining siblings, but no such differences were found when comparing IAA-positive and negative siblings. Siblings positive for ICA had PCA more often than did the ICA-negative siblings, whereas siblings positive for both ICA and PCA had increased levels of antibodies against CMF, BLG and BSA. These findings indicate that the humoral islet cell-associated autoimmunity characteristic of recent-onset childhood IDDM is clearly restricted to the islet cells and not directly related to signs of other organ-specific or non-organ-specific autoimmunity. The observation of increased levels of antibodies to cow's milk proteins in siblings positive for ICA suggests that the immune response to cow's milk proteins may be related to the progressive autoimmune process resulting in beta-cell destruction and ultimately in the clinical manifestation of IDDM. Gastrointestinal autoimmune mechanisms may play a role in the pathogenesis of IDDM, and the association observed between combined ICA and PCA positivity and increased levels of antibodies to cow's milk proteins in the siblings implies that there may be an enhanced transfer of nutritional antigens across the gut barrier in these subjects.

IgA bovine serum albumin antibodies are increased in newly diagnosed patients with insulin‐dependent diabetes mellitus, but the increase is not an independent risk factor for diabetes

We studied the significance of antibodies to bovine serum albumin (BSA) as a risk factor for insulin-dependent diabetes mellitus (IDDM) in a case-control setting. IgA and IgG antibodies to BSA and ovalbumin were measured from sera of 104 patients with newly diagnosed IDDM and of 111 matched controls by enzyme-linked immunosorbent assay. Patients with diabetes had significantly higher levels of IgA antibodies to BSA (p = 0.003); IgG antibodies also tended to be higher (p = 0.08). Levels of IgA antibodies to ovalbumin were similar in the patients and controls, but IgG antibodies were higher in controls (p = 0.02). When antibodies to BSA, beta-lactoglobulin, whole cow's milk and islet cell antibodies were studied as risk determinants of IDDM in a multivariate, logistic regression analysis, IgA antibodies to beta-lactoglobulin and to cow's milk were independently associated with the risk (p = 0.037 and 0.048, respectively), while antibodies to BSA were not a significant risk factor. The results question the role of BSA as a cross-reacting antigen with pancreatic beta-cell surface proteins in the aetiology of IDDM.

Mucosal IgA, mucosal cow's milk antibodies, serum cow's milk antibodies and gastrointestinal permeability in infants.

We have studied development of the levels of IgA cow's milk (CM) antibodies in the saliva, faeces and serum of 20 term and 20 preterm infants from birth to 8 months. All infants already had IgA in their saliva during the first week of life. The levels peaked at the age of one month, thereafter decreasing in both groups; from the age of three months levels remained stable. Term infants had higher levels than preterm infants, but no differences were found between breastfed and CM-fed infants. Breast-fed infants had higher levels of IgA in their faeces than did CM-fed infants; the IgA levels were similar in breast-fed term and preterm infants, being highest at birth, and decreasing thereafter. We also showed rising titers of serum IgA CM antibodies, with higher levels in infants regularly exposed to CM than in breast-fed infants. We sought associations between the magnitude of intestinal permeability to human alpha-lactalbumin (ALA) measured at the ages of 4-7 days and one month and the levels of IgG antibodies to CM, but no such relation was found.

Diet, cow's milk protein antibodies and the risk of IDDM in Finnish children

Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date- and sex-matched population-based control children in the nationwide "Childhood Diabetes in Finland" study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabetic-population-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM.

Diet, cow's milk protein antibodies and the risk of IDDM in Finnish children

Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date-and sex-matched population-based control children in the nationwide “Childhood Diabetes in Finland” study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabeticpopulation-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM.

Increased Levels of Cow's Milk and β-Lactoglobulin Antibodies in Young Children With Newly Diagnosed IDDM

To investigate the humoral immune response to cow's milk in pediatric patients with newly diagnosed IDDM. We measured IgA, IgG, and IgM antibodies to the proteins of cow's milk and to beta-lactoglobulin by an enzyme-linked immunosorbent assay. Samples from 706 pediatric patients with newly diagnosed IDDM were available. We used two comparison groups: 105 patients < 7 yr old had an unrelated age-matched control subject, and samples from 456 3- to 14-yr-old nondiabetic siblings also were available. Patients < 3 yr of age had a markedly higher median level of IgG and IgA antibodies to cow's milk compared with the control subjects (P = 0.03 and 0.002, respectively), IgG antibodies to beta-lactoglobulin also were higher (P = 0.03). Older groups of diabetic patients, 3.0-6.9 and 7.0-14.9 yr of age, had significantly higher levels of IgA antibodies to cow's milk and beta-lactoglobulin than the age-matched comparison groups of both unrelated control subjects and nondiabetic siblings, although the median values of the diabetic patients were closer to those of the comparison groups than in the youngest groups. Nondiabetic siblings had higher levels of IgA cow's milk antibodies than unrelated control subjects of similar ages (3-6.9 yr of age) (P = 0.03). The 14 siblings contracting IDDM during the follow-up showed no change in the levels of cow's milk or beta-lactoglobulin antibodies in relation to the clinical diagnosis. The results indicate an abnormally strong humoral response to the proteins of cow's milk, particularly in young IDDM patients and, to a lesser extent, in their siblings. We infer that the proteins of cow's milk may trigger the autoimmune process of IDDM.

The effect of maternal avoidance of eggs, cow's milk, and fish during lactation on the development of IgE, IgG, and IgA antibodies in infants

Serum levels of IgE, IgE antibodies to egg white (EW) and cow's milk (CM), IgG, and IgA antibodies to ovalbumin (OA) and β-lactoglobulin (BLG) were measured in a group of 115 infants with a family history of atopy/allergy at birth and at 3, 6, 9, 12, and 18 months of age. The mothers of 65 infants avoided eggs, CM, and fish during the first 3 months of lactation (maternal antigen avoidance diet, D group), whereas the remaining 50 mothers had no diet restrictions (no maternal antigen avoidance diet, ND group). CM was introduced after 6 months of age and EW after 9 months. The only statistically significant difference between the D and ND group infants was a lower rate of specimens with IgE antibodies to EW and/or CM in the infants at 3 months of age ( p = 0.008). IgE antibodies to EW and/or CM appeared in 62 infants during the study period and often during complete breast-feeding. In 40 of the infants, IgE antibodies appeared before the introduction of EW and CM into the diet. The IgE concentrations of the D and the ND group infants were similar. Cord-blood IgE was a poor predictor of atopy/allergy; for example, only seven of 103 infants with double heredity for atopy/allergy had values above the 90th percentile of our normal reference. The concentrations of IgG antibodies to OA and BLG were similar in the two groups. The levels decreased significantly ( p < 0.001) from birth to 6 months of age, indicating a passive placental transfer. From 6 months of age after the introduction of CM formulas, but not eggs, there was a rise in the IgG concentrations of antibodies to both OA and BLG, indicating that low doses of EW antigen in breast milk can evoke an IgG antibody response. Babies with high IgE responses to EW also had high IgG responses to OA.

Plasma antibodies to cow's milk are increased by early weaning and consumption of unmodified milk, but production of plasma IgA and IgM cow's milk antibodies is stimulated even during exclusive breast-feeding.

We measured levels of cow's milk-specific (CM) antibodies of immunoglobulin classes G, A and M by enzyme-linked immunosorbent assay in plasma of 198 healthy infants; a variable number of samples taken at birth and at ages of 2, 4, 6, 9, 12 and 28 months were available (altogether 765 samples). The rise in the level of IgG CM antibodies was highest and most rapid in infants exposed to CM formula before the age of 1 month. The level fell by 9 months, but rose again by 12 months. This second rise was attributed to the introduction of dairy milk. Partially breast-fed and fully weaned infants had similar levels of IgG CM antibodies. The levels of IgG CM antibodies were unaffected by the infants' own atopy, their heredity for atopy, and the umbilical serum level of IgG CM antibodies. IgA and IgM CM antibodies were absent at birth. Their levels increased similarly in exclusively breast-fed infants and infants fed CM formula. We conclude that plasma IgG antibodies to cow's milk are increased by early weaning and by consumption of unmodified cow's milk. Production of plasma IgA and IgM antibodies to cow's milk is stimulated even during exclusive breast-feeding.

20. MOTHERS OF INFANTS WITH COW'S MILK ALLERGY VS. CONTROLS HAVE LESS IgA ANTIBODIES TO COW'S MILK PROTEIN IN MILK AND PLASMA

During a follow-up of 198 infants from birth to age 12 months, 7 developed allergy to cow's milk. In 2 of these eczema appeared even during exclusive breast feeding (at ages 1 and 5 months), and in the others shortly after the introduction of cow's milk (between ages 3 and 10 months). The allergy was verified by test challenge in hospital. Of the 7 infants, 6 had supranormal plasma levels of IgE, and IgE antibodies to cow's milk. In the development of total and anti-cow's milk IgA, IgG and IgM plasma levels the 7 infants did not differ from the others. IgA antibodies to beta-lactoglobulin were lower in the mothers of the 7 infants than in the other mothers in colostrum and in milk 4 months post partum (p=0.05). There was no such difference in milk beta-lactoglobulin concentrations. The total IgA levels in milk were also lower in the 7 mothers throughout lactation; the difference was significant at 4 and 6 months post partum. The levels of IgG and IgM cow's milk antibodies were low in breast milk and showed no such difference. Plasma levels of IgA cow's milk antibodies were also lower in the mothers of the 7 infants than in the other mothers. We infer that inmunoglobulins in breast milk may influence the infant's immune responses to food antigens.