Cow's milk challenge through human milk evokes immune responses in infants with cow's milk allergy.

OBJECTIVES: In order to measure the immune response evoked in breast-fed infants with cow's milk allergy (CMA) by cow's milk challenge through human milk, mothers were given increasing doses of cow's milk after they had been on a cow's milk elimination diet. Another objective was to study the secretion of beta-lactoglobulin (BLG) into human milk before and during milk challenge in relation to the appearance of symptoms in infants. STUDY DESIGN: Seventeen asymptomatic mothers who had infants with challenge-proven CMA and 10 asymptomatic mothers who had healthy infants were recruited. Infants ranged in age from 1.8 to 9.4 months. A solid-phase enzyme-linked immunoassay (ELISPOT) was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells. Flow cytometry was used to enumerate different lymphocyte subpopulations among peripheral blood lymphocytes primed during provocation by cow's milk antigens. BLG levels were assessed in human milk before the challenge and 1, 2, 3, and 4 hours after the commencement of the challenge. RESULTS: All but one of the infants with CMA showed symptoms of CMA during cow's milk challenge through human milk. There was a significant rise in the total number of immunoglobulin-secreting cells in the IgA and IgG classes associated with a positive cow's milk challenge response, but the proportions of peripheral blood B cells bearing CD19, CD23, CD19 and 23, CD5, or CD19 and CD5 were comparable. BLG levels were comparable in both study groups. CONCLUSIONS: Most of the infants with CMA reacted to cow's milk challenge through human milk. Hypersensitivity reactions to food antigens through human milk may be more common than previously thought.     

Defective tumor necrosis factor-α production in infants with cow’s milk allergy

As an aid to clarifying the role of immune mechanisms in the development of cow’s milk allergy (CMA) in suckling infants, we studied the capacity of peripheral blood mononuclear cells (PBMC) to produce tumor necrosis factor-α (TNF-α) in vitro. The study population consisted of 43 infants, aged 0.12–11.2 months; of these, 31 had challenge-proven cow’s milk allergy manifested with either skin or gastrointestinal symptoms or both. In addition, 12 healthy infants were studied as controls. The spontaneous, unstimulated and mitogen-induced production of TNF-α and interferon-γ (IFN-γ) by isolated peripheral blood leukocytes was evaluated. TNF-α and IFN-γ production of PBMC was significantly lower in infants with cow’s milk allergy than in healthy children. Our results indicate that, in infants with CMA, the function of TNF-α-producing cells is defective. This might disturb the development of oral tolerance and thereby lead to cow’s milk allergy. These results may help to clarify the etiopathology of CMA.     

Immunologic disturbances in cow's milk allergy, 2: evidence for defective interferon-gamma generation

We have investigated the role of interferon-gamma (IFN-gamma) in the regulation of antigen-specific T-cell function in patients with cow's milk allergy. The study population consisted of 22 patients, aged from 7. 6 to 56. 9 months, who had challenge-proven cow's milk allergy (CMA) manifested with either skin (n=9) or gastrointestinal (n=13) symptoms. In addition, 11 age-matched children and 6 adults, mean (SD) age 31 (7) years, were studied as controls. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The spontaneous and mitogen-induced IFN-gamma and interleukin-4 (IL-4) generation of isolated lymphocytes was evaluated in vitro with commercial ELISA Kits at diagnosis and at reassessment. At diagnosis, the IFN-gamma production was not detectable in patients with CMA as compared with control children. IL-4 production was almost undetectable in all subjects in this study. However, at reassessment the CMA patients who had acquired clinical tolerance to cow's milk (n=16) showed enhanced IFN-gamma production, when compared with that of control children, but still lower when compared with that of healthy adults. Our results indicate that the maturation of IFN-gamma producing T-cells is delayed in CMA, which could lead to a disturbance in the regulation of T-cell function. This defect might be an important etiologic factor for CMA.     

Low frequency of CD4+, but not CD8+, T cells expressing interferon‐γ is related to cow's milk allergy in infancy

Low interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) production in peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis and food allergy have been reported previously. However, it remains unclear whether the weak cytokine production is caused by the imbalance of specific T‐cell subsets or by dysregulation of T‐cell function. In the present study we investigated the intracellular expression of these cytokines at a single‐cell level to clarify the background of the disruption. Twelve of 27 breast‐fed infants (0.1–8.8 months of age) had challenge‐proven cow's milk allergy (CMA), and 15 infants were studied as a healthy control group. PBMC were stimulated with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The frequencies of the cells expressing intracellular IL‐4, IFN‐γ, and TNF‐α were assessed using flow cytometry. In addition, at this time‐point leucocyte subsets from the milk of mothers of these infants were evaluated using light microscopy. A lower number of CD8⁺ T cells and the defective capability of CD4⁺ T cells to express IFN‐γ in infant's peripheral blood co‐existed with a lower number of macrophages in their mother's milk.     

Cow's milk allergy in infants with atopic eczema is associated with aberrant production of interleukin-4 during oral cow's milk challenge

OBJECTIVES: A failure in the establishment and maintenance of oral tolerance in infancy may result in food allergy. To further assess the role of the intestinal immune system in cow's milk allergy (CMA), we investigated the systemic production of the pro-allergenic Th2 cytokine interleukin (IL)-4 and anti-allergenic cytokines IL-10, transforming growth factor (TGF)-beta1 and TGF-beta2 in infants suffering from atopic eczema with and without CMA during antigen elimination diet and oral antigen exposure. METHODS: 18 infants (mean age, 9.6 months; 95% confidence interval 8.1-11.1 months) with atopic eczema and CMA and 17 infants (mean age, 9.7 months; 95% confidence interval 8.6-10.9 months) with atopic eczema tolerant to milk as assessed by a double blind, placebo-controlled cow's milk challenge were investigated. Peripheral blood mononuclear cells were obtained during antigen elimination diet and during oral cow's milk challenge and stimulated with Concanavalin-A or cow's milk or were left unstimulated. The cytokine concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: During antigen elimination, the Concanavalin A-stimulated production of TGF-beta2 was significantly lower in infants with CMA as compared with infants without CMA: 129 pg/mL (interquartile ratio, 124-144 pg/mL) vs. 149 pg/mL (interquartile ratio, 133-169 pg/mL); P = 0.016. During oral antigen exposure, the immune responses in infants with CMA were characterized by significantly higher spontaneous production of IL-4 as compared with those without CMA: 12.0 pg/mL (interquartile ratio, 5.2-28.3 pg/mL) vs. 4.2 pg/mL (interquartile ratio, 1.5-7.6 pg/mL); P = 0.018. CONCLUSIONS: Infants with atopic eczema and CMA exhibit markedly increased systemic pro-allergenic IL-4 responses on intestinal antigen contact, which may partially be explained by a defective ability to launch anti-allergenic TGF-beta2 responses.     

Immunologic disturbances in cow's milk allergy, 1: delayed maturation of suppressor activity

To assist in identifying pathogenetic mechanisms in different subtypes of cow's milk allergy (CMA), the function of immunoregulatory T-lymphocytes was studied. The study population consisted of 23 patients, mean [95% confidence interval] age of 25. 6 [19. 5, 33. 6] months, who had challenge-proven cow's milk allergy manifested with either skin (n=9) or gastrointestinal (n=14) symptoms; in addition, 13 age-matched disease controls were studied. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The suppressor activity of isolated lymphocytes was measured in vitro by a cell coculture at rechallenge and in 10/23 patients at diagnosis. At diagnosis, patients with CMA (n=10) showed a decreased mean [95% CI] suppressor activity, induced by either Concanavalin A, 7[-2, 15]%, or cow's milk, 3[-8, 14]% as compared with disease controls (n = 13), 19[15, 24]% and 24[17, 31]%; F = 7. 1, p = 0.004 and F = 6. 7, p = 0.005, respectively. At rechallenge the suppressor activity, induced both by Concanavalin A and cow's milk, reached the level of disease controls only in patients who had acquired clinical tolerance to cow's milk (n = 13/23), but not in those retaining CMA (n = 10/23). Our results indicate that the maturation of suppressor function is delayed in CMA, which might be of primary importance in the etiopathogenesis of CMA.     

Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy

To cite this article: Savilahti EM, Viljanen M, Kuitunen M, Savilahti E. Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy. Pediatric Allergy Immunology 2012: 23: 590-596. ABSTRACT: 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?相似文献   

Evidence for eosinophil activation in cow's milk allergy

To assist in identifying pathogenetic mechanisms in different clinical manifestations of cow's milk allergy (CMA), the involvement of eosinophil cells in immunoinflammatory reactions was evaluated. The study population comprised 28 patients, aged from 5.8 to 43.0 months, who had challenge-proven CMA, manifested either cutaneously (n = 17) or gastrointestinally (n = 11). A clinical cow's milk challenge was performed in hospital after a 4 week cow's milk elimination period. Eosinophil activation in vivo was studied by measuring the serum level of eosinophil cationic protein (ECP) before the oral cow's milk challenge, mean (SD) 27 (12) hours after commencing the challenge and one week later. These results were compared to those of 80 non-allergic age-matched controls. During the challenge, the level of ECP increased from 6.2 (4.5, 8.0) μg/L to 20.0 (9.5, 30, 4) μg/L in CMA patients with skin manifestations but not in those with gastrointestinal symptoms. The increase was shown to be transient. We conclude that eosinophil degranulation is an important immunologic mechanism leading to allergic inflammation in cutaneously manifested CMA.     

Intestinal cow's milk allergy

Cow's milk allergy (CMA) is multifaceted disease representing systemic, skin or gastrointestinal reactions to cow's milk (CM) protein. This article shortly reviews the intestinal form of CMA (ICMA). According us the child is allergic to CM when the immunologic reaction to CM is associated with clinical symptoms. The incidence of CMA is 1.3-1.9% in general, but the ICMA only 0.6 pro mille among the children less than six months of age. The majority of infants shows symptoms within a month of starting CM feeding. The majority of children with CMA have gastrointestinal symptoms. Manx of these infants has additionally dermatological symptoms and some respiratory symptoms. The mode of onset is often acute diarrhoea and vomiting, as in acute gastroenteritis. Laboratory findings indicate iron deficiency anemia in 20-70%. Half to two thirds of infants with chronic diarrhoea have moderate to severe steatorrhoea. The morphologic lesion in the gastrointestinal tract in ICMA is widespread, often being present from stomach to rectum. Jejunal lesion is most severe in the proximal part of the intestine and nowadays most patients have only partial villous atrophy or slight changes of the villi. Both the epithelium and the lamina propria of the jejunum are infiltrated with inflammatory cells. The morphology of the small intestine speaks for a strong immune reaction which leads increased destruction of surface epithelial cells. We recommend elimination of CM proteins to the age of 1.5 to 2 years. Most patients tolerate CM by the age of 2 years without symptoms. Prolonged breast-feeding and avoidance of early contact with CM are important in reducing the severity and frequency of CMA.     

Cow's milk allergy, incidence and pathogenetic role of early exposure to cow's milk formula

A study was performed in infants under the age of 12 months born during 1974 and admitted to St. G?ran's Children's Hospital with symptoms suggestive of cow's milk allergy (CMA). The aims of the study were to determine the role of early exposure to cow's milk formulas as a predisposing factor to CMA and to estimate the incidence of CMA in infancy. Twenty-five infants fulfilled the criteria for CMA. Available records were reviewed and a careful history was obtained from the mothers on two occasions. The patient group was compared with a control group. Sixteen of the 25 infants were exposed to cow's milk protein during their first week in the nursery for newborns, 6 were exposed before the end of the fourth week of life, and 3 infants were apparently not exposed. All infants were breast fed 3 to 26 weeks before re-exposure and occurrence of symptoms. Infants with CMA were given cow's milk formulas during their first 4 weeks of life significantly more often than infants in the control group (p less than 0.01). The incidence of CMA was approximately 1 : 200. The first 4 weeks after birth seem to be a particularly vulnerable period. Hence, in order to prevent CMA, infant formula should not be given--even occasionally--during this period.     

T-cell signal transduction in children with cow's milk allergy – increased MAP kinase activation in patients with acute symptoms of cow's milk allergy

The precise immune mechanisms behind cow's milk allergy (CMA) are still unknown. Previously, the production of the cytokines TNF-α and IFN-γ in T cells from children with CMA has been shown to be decreased, and the production of IL-4 has been shown to be increased when compared to healthy children. As these aberrations in cytokine production may be associated with disturbances in cellular function, we investigated whether T-cell signal transduction is abnormal in children with CMA. For this purpose we evaluated the activation of the MAP kinase Erk2. Thirty-nine infants were included in the study. Of those with CMA, 13 had acute symptoms and 9 were free of symptoms due to a successful elimination diet at the time of the study. To activate T cells and to stimulate MAP kinase phosphorylation, peripheral blood mononuclear cells (PBMC) were incubated with Concanavalin A (ConA). The change in MAP kinase phosphorylation was measured by Western blotting. The increase in MAP kinase phosphorylation after stimulation with ConA for 5 min was significantly higher in cells from patients with acute symptoms of CMA than in cells from CMA patients free of symptoms or cells from healthy children. A time-course experiment showed that the change in MAP kinase phosphorylation was still increasing after 10 min incubation in cells from patients with acute symptoms of CMA. The increased MAP kinase activation was found to correlate positively with non-IgE mediated CMA in patients with acute symptoms of CMA.     

Bovine beta-lactoglobulin in the human milk. A longitudinal study during the whole lactation period

Human milk samples (n = 232) collected during the whole lactation period from 25 healthy, Swedish mothers were analyzed by radioimmunologic method for content of bovine beta-lactoglobulin. Detectable amounts (5-800 micrograms/l) were found in 93 of 232 milk samples (40%). Six mothers had no detectable beta-lactoglobulin in their breast milk on any occasion. Two mothers had measurable beta-lactoglobulin in all their milk samples. No correlation was found between daily cow's milk intake and concentration of beta-lactoglobulin in the milk samples. Six mothers with allergic symptoms such as asthma, hay-fever, eczema all had detectable amounts of beta-lactoglobulin in their milk. Of 19 mothers without allergy, 13 had detectable amounts. This difference did not show statistical significance. The presence of symptoms in the infant such as diarrhoea, vomiting, colic, exanthema was significantly correlated to high levels of beta-lactoglobulin in the milk. Bovine beta-lactoglobulin was also detected in 7 of 13 serum samples. The two mothers with detectable beta-lactoglobulin in all milk samples had the highest serum values, and their infants suffered from gastro-intestinal symptoms, weight decline and exanthema.     

Bovine β-Lactoglobulin in the Human Milk

ABSTRACT. Human milk samples ( n =232) collected during the whole lactation period from 25 healthy, Swedish mothers were analyzed by radioimmunologic method for content of bovine β-lacto-globulin. Detectable amounts (5-800 μ/1) were found in 93 of 232 milk samples (40%). Six mothers had no detectable β-lactoglobulin in their breast milk on any occasion. Two mothers had measurable /Mactoglobulin in all their milk samples. No correlation was found between daily cow's milk intake and concentration of β-lactoglobulin in the milk samples. Six mothers with allergic symptoms such as asthma, hay-fever, eczema all had detectable amounts of β-lactoglobulin in their milk. Of 19 mothers without allergy, 13 had detectable amounts. This difference did not show statistical significance. The presence of symptoms in the infant such as diarrhoea, vomiting, colic, exanthema was significantly correlated to high levels of β-lactoglobulin in the milk. Bovine β-lactoglobulin was also detected in 7 of 13 serum samples. The two mothers with detectable β-lactoglobulin in all milk samples had the highest serum values, and their infants suffered from gastro-intestinal symptoms, weight decline and exanthema.     

Lymphocyte response to cow's milk proteins in patients with cow's milk allergy: relationship to antigen exposure

The cellular immune response to cow's milk was measured in patients with challenge-proven cow's milk allergy (CMA), manifested with either gastrointestinal or skin symptoms. After 2–4 weeks on milk elimination, 44 children, mean (SD) age 15.7 (9.4) months, were challenged, and cow's milk-induced lymphocyte transformation was measured before the clinical challenge (Day 1) and / or one week later (Day 8). During the clinical challenge period, 17 (39%) patients showed gastrointestinal reactions, 9 (20%) had urticarial or eczematous skin eruptions, and 18 (41%) were negative to challenge. On Day 1, the mean [95% confidence interval] stimulation index for lymphocytes in patients manifesting CMA with gastrointestinal symptoms, 2.60 [1.60, 4.10], was significantly higher than that in patients with skin symptoms, 1.15 [0.60, 2.30], or patients with negative clinical challenge, 0.83 [0.64, 1.08], F = 9.0, p = 0.001. After the clinical challenge (Day 8), this cow's milk-induced lymphocyte proliferation response was abrogated. At the same time, CMA patients evidenced a significantly higher spontaneous lymphocyte proliferation response in RPMI medium-containing control cultures than those with negative clinical challenge. We conclude that in patients with CMA, the number of circulating cow's milk-sensitized lymphocytes is depleted or their function is impaired after clinical exposure to cow's milk antigens.     

Decrease in the antioxidant capacity of red blood cells in children with celiac disease.

The erythrocyte glutathione metabolism of 11 children with acute celiac disease (CD), 11 children under gluten free diet with CD and 5 children with cow's milk allergy was compared to that of 11 children with nutritive iron deficiency and to 22 healthy children as controls. Erythrocyte glutathione (GSH) content of celiac children was elevated and the glutathione disulfide (GSSG) level was significantly decreased as compared to normal controls. Erythrocyte GSSG/GSH ratio in acute CD differed also from the one in iron deficiency. In vitro oxidative load of acetylphenylhydrazine proved the impaired glutathione stability of the erythrocytes in acute CD and cow's milk allergy. A parallel rise of methemoglobin and hemichrome level of blood cells was seen. Further on, the selenium content of the red blood cells of CD patients decreased. All alterations of the erythrocyte tended to normalize during the dietetic period. These data suggest a reduced protective capacity of erythrocytes in CD and in cow's milk allergy in childhood against oxidizing stresses.     

Cow's milk and intestinal blood loss in late infancy

OBJECTIVES: Young infants commonly show occult intestinal blood loss when fed cow's milk, but in older infants blood loss may be less common. This study examined intestinal blood loss in response to cow's milk feeding in normal 7(1/2)-month-old and 12-month-old infants. STUDY DESIGN: Infants (n = 62) were fed formula for 1 month and then pasteurized cow's milk for 2 months. Stools were collected for quantitative determination of hemoglobin. Iron nutritional status was assessed. RESULTS: Infants fed cow's milk from 7(1/2) months of age showed a significant increase in guaiac-positive stools and in stool hemoglobin concentration. These effects were largely limited to those infants who had been breast fed early in life. Infants fed cow's milk from 12 months of age at baseline had greater stool hemoglobin concentrations than 7(1/2)-month-old infants, but cow's milk produced no significant increase. In neither age group did cow's milk affect iron nutritional status. CONCLUSION: The response to cow's milk is attenuated in infants aged 7(1/2) months compared with younger infants. By 12 months of age, the response has disappeared entirely. We conclude that the gastrointestinal tract of healthy infants gradually loses its responsiveness to cow's milk.     

Eosinophil cationic protein in human milk is associated with development of cow's milk allergy and atopic eczema in breast-fed infants

The precise role of leukocytes and mediators in human milk is still unresolved. Eosinophils are uncommonly detected in human milk and their presence has previously been associated with maternal atopy and development of cow's milk allergy (CMA) in the breast-fed infant. The purpose of this study was to examine the levels of eosinophil cationic protein (ECP) in human milk and to compare the levels with development of allergic diseases in breast-fed infants. Altogether 94 breast-feeding mothers (58 atopic, 36 nonatopic) with their babies were prospectively followed from birth for development of CMA or atopic dermatitis. Colostrum and mature milk samples (at 3 mo of lactation), together with mother's peripheral blood samples, were collected. Milk and blood leukocyte content was evaluated with a light microscope. ECP concentration in human milk was measured by commercial UniCAP method. By the end of a 2-y follow-up, 51 mothers had an infant with CMA, 24 had an infant with atopic dermatitis, and 19 had a healthy infant. ECP concentration in milk was under the detection limit (2 microg/L) in all the mothers with a healthy infant, whereas detectable levels were found in 27% of mothers with a CMA infant and in 42% of those with a baby with atopic dermatitis. Measurable ECP in milk was detected in 26% of the atopic and 25% of the nonatopic mothers. Presence of ECP in human milk is associated with development of CMA and atopic dermatitis in the breast-fed infant, but has no direct association with the maternal atopy.     

COW'S MILK ALLERGY, INCIDENCE AND PATHOGENETIC ROLE OF EARLY EXPOSURE TO COW'S MILK FORMULA

Abstract. A study was performed in infants under the age of 12 months born during 1974 and admitted to St. Göran's Children's Hospital with symptoms suggestive of cow's milk allergy (CMA). The aims of the study were to determine the role of early exposure to cow's milk formulas as a predisposing factor to CMA and to estimate the incidence of CMA in infancy. Twenty-five infants fulfilled the criteria for CMA. Available records were reviewed and a careful history was obtained from the mothers on two occasions. The patient group was compared with a control group. Sixteen of the 25 infants were exposed to cow's milk protein during their first week in the nursery for newborns, 6 were exposed before the end of the fourth week of life, and 3 infants were apparently not exposed. All infants were breast fed 3 to 26 weeks before re-exposure and occurrence of symptoms. Infants with CMA were given cow's milk formulas during their first 4 weeks of life significantly more often than infants in the control group ( p <0.01). The incidence of CMA was approximately 1:200. The first 4 weeks after birth seem to be a particularly vulnerable period. Hence, in order to prevent CMA, infant formula should not be given—even occasionally—during this period.     

A Prospective Study of Cow's Milk Allergy in Exclusively Breast-Fed Infants

ABSTRACT. A cohort of 1749 newborns in the municipality of Odense were followed prospectively for the development of cow's milk allergy (CMA) during their first year of life. Altogether 39 fulfilled the criteria for CMA (2.2%). Out of the 39 infants, 17 developed symptoms of CMA during breast-feeding, in all cases before the age of 3 months. Nine of these were solely breast-fed at the time of diagnosis, giving a one year incidence of CMA in exclusively breastfed infants of 0.5% (9/1 749) in a study population with a frequency of exclusive breast-feeding of 52% at 3 months of age. None of the infants had signs of CMA in the neonatal period. Review of records from the newborn nursery revealed that all 9 infants had been exposed to cow's milk formula in amounts corresponding to approximately 0.4-3.0 g of Beta-lactoglobulin (BLG) during the first three days of life. Human milk samples were analyzed by enzyme-linked immunosorbent assay (ELISA) for the content of bovine BLG. Detectable amounts (0.5–45 ng/ml) were found in 3/9 samples of human milk against which the infants reacted clinically. Analysis of the size distribution by high pressure liquid gel permeation chromatography in combination with ELISA indicated a molecular weight of BLG corresponding to that of monomeric BLG (18 kD). Possibly early inadvertent and occasional exposure to cow's milk proteins may initiate sensitization in predisposed neonates. Subsequent exposure to minute amounts of bovine milk proteins in human milk may act as booster doses eliciting allergic reactions.     

A prospective study of cow's milk allergy in exclusively breast-fed infants. Incidence, pathogenetic role of early inadvertent exposure to cow's milk formula, and characterization of bovine milk protein in human milk

A cohort of 1,749 newborns in the municipality of Odense were followed prospectively for the development of cow's milk allergy (CMA) during their first year of life. Altogether 39 fulfilled the criteria for CMA (2.2%). Out of the 39 infants, 17 developed symptoms of CMA during breast-feeding, in all cases before the age of 3 months. Nine of these were solely breast-fed at the time of diagnosis, giving a one year incidence of CMA in exclusively breast-fed infants of 0.5% (9/1,749) in a study population with a frequency of exclusive breast-feeding of 52% at 3 months of age. None of the infants had signs of CMA in the neonatal period. Review of records from the newborn nursery revealed that all 9 infants had been exposed to cow's milk formula in amounts corresponding to approximately 0.4-3.0 g of beta-lactoglobulin (BLG) during the first three days of life. Human milk samples were analyzed by enzyme-linked immunosorbent assay (ELISA) for the content of bovine BLG. Detectable amounts (0.5-45 ng/ml) were found in 3/9 samples of human milk against which the infants reacted clinically. Analysis of the size distribution by high pressure liquid gel permeation chromatography in combination with ELISA indicated a molecular weight of BLG corresponding to that of monomeric BLG (18 kD). Possibly early inadvertent and occasional exposure to cow's milk proteins may initiate sensitization in predisposed neonates. Subsequent exposure to minute amounts of bovine milk proteins in human milk may act as booster doses eliciting allergic reactions.