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At least 19 recordsLinked to original sources
PubMed1999

A murine model of IgE-mediated cow's milk hypersensitivity.

BACKGROUND: Cow's milk allergy (CMA) is one of the leading causes of food allergy in children. Understanding the mechanisms involved in the development of CMA has been hampered by the lack of suitable animal models. OBJECTIVE: We sought to develop a mouse model of IgE-mediated cow's milk hypersensitivity (CMH) that mimics the clinical features of immediate CMA in humans. METHODS: Three-week-old C3H/HeJ mice were sensitized by intragastric administration of cow's milk (CM) plus cholera toxin and boosted 5 times at weekly intervals. RESULTS: CM-specific IgE antibody levels were significantly increased at 3 weeks and peaked at 6 weeks after the initial feeding. Intragastric challenge with CM at week 6 elicited systemic anaphylaxis accompanied by vascular leakage, significantly increased plasma histamine, and increased intestinal permeability to casein. Histologic examination of intestinal tissue revealed marked vascular congestion, edema, and sloughing of enterocytes. The role of IgE in mediating CMH was confirmed by abrogation of passive cutaneous anaphylaxis reactions by heat inactivation of immune sera. Development of IgE-mediated CMH in this model is likely to be TH2 cell mediated because in vitro stimulation of spleen cells from mice allergic to CM induced significant increases in the levels of IL-4 and IL-5, but not IFN-gamma. CONCLUSION: This model should provide a useful tool for evaluating the immunopathogenic mechanisms involved in CMA and for exploring new therapeutic approaches.

Adjuvants, Immunologic↗
PubMed1998

Milk hypersensitivity--key to poorly defined gastrointestinal symptoms in adults.

Lactose intolerance is a common adverse reaction to milk in adults, while milk hypersensitivity is a disorder of infancy. We hypothesized that milk hypersensitivity may cause many unspecific gastrointestinal disorders in adults. Twenty adults were subjected to double-blind, placebo-controlled milk challenge. Phagocyte activity, and Fc gamma and complement receptor expression of phagocytes were assayed, and serum total IgE, milk-specific IgE, and serum reactivity to milk protein were determined. The challenge increased phagocyte activity and complement receptor expression of phagocytes in subjects designated milk-hypersensitive, who had gastrointestinal symptoms from milk ingestion but normal lactose tolerance. The increase was not detected in lactose-intolerant or control subjects. The milk-hypersensitive group was also distinguished from the lactose-intolerant group by enhanced serum reactivity to milk protein. Only two out of nine milk-hypersensitive subjects had detectable milk-specific serum IgE. It is concluded that milk hypersensitivity in adults, occurring as gastrointestinal reactions, may be more common than previously thought.

Adult↗
PubMed1999

Milk hypersensitivity in young adults.

OBJECTIVE: To estimate the prevalence of milk hypersensitivity in Finnish adults. DESIGN: Cross-sectional study. SUBJECTS: Two hundred men and 206 women aged 27 y randomly recruited from the population register in southwestern Finland. INTERVENTIONS: The subjects were interviewed about their dairy product consumption, abdominal discomfort after dairy product intake and lactose intolerance. From serum samples, serum reactivity to milk protein and milk-specific IgG1, IgG2, IgG3 and IgA were measured. RESULTS: About 20% of the subjects reported abdominal discomfort after dairy product intake, whereas only 6.4% had been diagnosed to have lactose intolerance. The amount of milk consumed correlated well with the serum assay results in subjects reporting abdominal discomfort but not in subjects who were free from these symptoms. Among subjects with no record of dairy product restriction or lactose intolerance, those experiencing abdominal discomfort after dairy product intake had significantly higher serum reactivity to milk protein than those without such discomfort. The concentrations of serum milk-specific antibodies did not differ between these two groups. The prevalence of milk hypersensitivity in this population was estimated to be 3-6%. CONCLUSIONS: Milk hypersensitivity may be as common in adults as in infants. The measurement of serum reactivity to milk protein may prove useful in screening milk hypersensitivity in subjects who have not restricted their dairy product consumption.

Abdominal Pain↗
PubMed1995

Clinical trials of Astemizol in children with cow's milk hypersensitivity.

A group of 36 children aged from 1 10/12 to 11 years was the subject of clinical and laboratory examinations. It was found that there is a close relationship between food hypersensitivity to milk and symptoms of the skin (81%), upper (61%) and lower (55%) respiratory tract, digestive tract (47%) and central nervous system (14%). These symptoms occured in isolated or associated forms on the different organs or systems. An elimination diet and pharmacological treatment with Astemizol were used in all children from the investigated group. Complete relief of symptoms was observed in 39% of children; 44% of examined patients had a regression of symptoms of 1 and/or 2 organs. Side effects of treatment with Astemizol were observed in the form of excessive appetite (22%), body weight gain (3%), vomiting (3%), diarrhoea (3%), bleeding from the nose (3%), sleepiness (5%). Due to the good therapeutic effect and insignificant side effects, the supporting pharmacological treatment with Astemizol was found useful in children with hypersensitivity to cow's milk.

Anti-Allergic Agents↗
PubMed1983

Milk hypersensitivity. I. Pathogenesis and symptomatology.

Milk hypersensitivity is a problem that can have substantial health, financial and social implications. The condition is underdiagnosed by some physicians and overdiagnosed by others probably because its symptoms are varied and shared with many other diseases. The gap in our knowledge on the pathogenesis of various manifestations of CMA has been only partly bridged by the information accumulated in recent years. It has become clear that milk-sensitive patients are heterogeneous, both regarding symptomatology and underlying pathogenic mechanisms.

Allergens↗
PubMed2004

Severe gastroesophageal reflux disease and cow milk hypersensitivity in infants and children: disease association and evaluation of a new challenge procedure.

BACKGROUND: Gastroesophageal reflux disease (GERD) and cow milk hypersensitivity are frequent disorders of infancy. A possible causative association between these two entities has been suggested. OBJECTIVE: The primary aim was to elucidate whether a causative relationship between the two entities could be established in a population of infants and children. A secondary aim was to evaluate whether cow milk challenge during esophageal pH monitoring is useful as an objective method to identify this subgroup of patients. METHODS: Upper endoscopy followed by a 48-hour esophageal pH monitoring with cow's milk elimination diet at day 1 and challenge at day 2. Cow milk hypersensitivity was later verified by elimination diet and a second open (in patients < 3 years of age) or double-blind placebo-controlled (in patients > or = 3 years of age) challenge. Skin prick test, specific serum immunoglobulin E and skin patch test were used as supplementary procedures. Follow-up endoscopy and pH monitoring were performed after 3 months of treatment (omeprazole versus elimination diet dependent on evidence of food hypersensitivity). RESULTS: Eighteen of 42 investigated patients had severe GERD, defined as endoscopic esophagitis and/or a reflux index > 10%. Among these patients, a group of 10 patients with GERD and cow milk hypersensitivity was identified. This group had a significantly higher reflux index compared with children with primary GERD. No significant increase was noted in reflux index during simultaneous pH monitoring and milk challenge. CONCLUSIONS: An association between GERD and cow milk hypersensitivity was observed in both infants and children with severe GERD. Simultaneous cow milk challenge and pH monitoring had limited value as a method to identify this subgroup.

Adolescent↗
PubMed2001

Differences in the gut bacterial flora of healthy and milk-hypersensitive adults, as measured by fluorescence in situ hybridization.

We enumerated the predominant gut genera from fecal samples of nine healthy and eight milk-hypersensitive adults both before and after 4 weeks Lactobacillus rhamnosus GG (LGG) supplementation. The anaerobic intestinal microflora of milk-hypersensitive adults was found to resemble that of healthy adults. LGG-consumption resulted in a significant increase in the number of bifidobacteria in healthy but not in milk-hypersensitive subjects, as well as a general increase in bacterial numbers in all other bacterial genera tested in both groups. In conclusion, the composition of the gut microbiota in milk-hypersensitive adults appears to be normal. LGG may have potential in reinforcing the endogenous flora.

Adult↗
PubMed1998

Probiotic bacteria down-regulate the milk-induced inflammatory response in milk-hypersensitive subjects but have an immunostimulatory effect in healthy subjects.

BACKGROUND: Probiotic bacteria can influence immune responses both specifically by stimulating antibody production and nonspecifically by enhancing phagocytosis of pathogens and modifying cytokine production. OBJECTIVE: The authors hypothesized that probiotic bacteria can alleviate hypersensitivity by influencing phagocytes. The modulation of phagocytes may be different in healthy subjects compared with hypersensitive subjects. SUBJECTS AND METHODS: In a double-blind, cross-over study, challenges with milk in milk-hypersensitive and healthy adults with or without an intestinal bacterial strain, Lactobacillus GG (ATCC 53103) were performed. The challenge-induced immunoinflammatory response was recorded by measuring the expression of phagocytosis receptors prior to and after the challenge using flow cytometry. RESULTS: In milk-hypersensitive subjects, milk challenge increased significantly the expression of CR1, FcgammaRI and FcalphaR in neutrophils and CR1, CR3 and FcalphaR in monocytes. Milk with Lactobacillus GG prevented the increase of the receptor expression. In healthy subjects, milk challenge did not influence receptor expression while milk with Lactobacillus GG increased significantly the expression of CR1, CR3, FcgammaRIII and FcalphaR in neutrophils. CONCLUSION: Probiotic bacteria appear to modulate the nonspecific immune response differently in healthy and hypersensitive subjects. This is seen as an immunostimulatory effect in healthy subjects, and as a down-regulation of immunoinflammatory response in milk-hypersensitive subjects.

Adult↗
PubMed1983

Milk hypersensitivity. II. Practical aspects of diagnosis, treatment and prevention.

To date the most reliable procedure for the diagnosis of milk hypersensitivity is a properly conducted elimination-challenge test. Several in vitro tests have been developed but because of the diverse underlying mechanisms of hypersensitivity reactions to milk developing a single laboratory test that can be universally positive in every patient would be rather difficult. However, with a better categorization of milk-sensitive patients, together with the development of relevant, standardized and practical tests, the laboratory diagnosis of milk allergy should become more reliable. Milk hypersensitivity can be effectively treated and is largely preventable. Avoidance is the most effective mode of treatment and results in a good prognosis. In instances where the desired degree of avoidance cannot be attained pharmacologic agents may be of help. The need still exists for developing an effective procedure of hyposensitization. For prevention, prolonged breast feeding should be recommended, especially in infants of atopic families.

Animals↗
PubMedDate not supplied

[Interleukin 13 and 18 serum concentration in children with cow milk hypersensitivity].

UNLABELLED: The aim of the study was the estimation of IL-13 and IL-18 concentration in serum of children with cow milk hypersensitivity and estimation of its usefulness in clinical practice. MATERIAL AND METHODS: 30 children (14 boys, 16 girls) at the age 6-24 months, average 10.5 months. The children were divided into two groups. Group 1 included 18 children with elevated total IgE, group II, 12 children with normal IgE. In all children with suspected cow milk hypersensitivity, a diet based on strong milk hydrolysates or soy-milk formulas was advised. In 10 children IL-13 and IL-18 were examined three times: at the moment of diagnosis and after 3 and 6 months of dietary treatment. In 20 children IL-13 and IL-18 were estimated twice. Total IgE and specific IgE were performed by HYTER 288; IL-13 and IL-18 were measured by Bender Med System. The results were analysed statistically. RESULTS: in children with elevated IgE statistically significant higher IL-13 concentration was found and the mean IL-18 concentration in this group was lower but the difference was not statistically significant. We confirmed a positive correlation between elevated IgE and IL-13 concentration and a negative correlation between IgE and IL-18 before introducing the diet. In children with clinical improvement there was a nonsignificant decrease of IL-13 and increase of IL-18 concentration after diet introduction. In the group without clinical improvement, high IL-13 and low IL-18 concentration during diet were observed (p < 0,01). Highly positive correlation between serum IL-18 after 3 months of elimination diet and clinical improvement was observed. Highly negative correlation between mean IL-13 concentration after 6 months of diet and the clinical condition were observed. CONCLUSIONS: The correlation between IL-13 concentration and elevated IgE, indicates a connection of this cytokine with atopy. Negative correlation between IL-18 concentration and elevated IgE suggests a possibility of inhibiting IgE synthesis by this cytokine. A strong correlation between IL-18 concentration and clinical improvement after 3 months of elimination diet may imply a reduction of the allergic process. High negative correlation between IL-13 concentration and clinical improvement after 6 months of elimination diet may indicate a prolongation of the allergic process.

Animals↗
PubMed2000

[Intestinal flora of infants with cow milk hypersensitivity fed on casein-hydrolyzed formula supplemented raffinose].

We studied the intestinal flora of infants with cow milk hypersensitivity fed on casein-hydrolyzed formula (MA-1) and the influence of that supplemented with Raffinose (MA-1[R]). Infants with cow milk hypersensitivity were fed with MA-1 for 2 weeks, after which the formula was changed to MA-1[R]. Fourteen subjects were enrolled in this study and divided into two groups; three who fed with breast or conventional milk in addition to MA-1 or MA-1[R](BM group) and 11 mainly fed with MA-1 or MA-1[R] (TF group). Intestinal flora was investigated at two weeks after MA-1 feeding and at two weeks after MA-1[R] feeding, respectively. Bifidobacterium was detected as the most predominant bacteria in all examples in the BM group, and that count and the ratio in all bacteria remained high even after changing MA-1 to MA-1[R]. On the other hand, bacteria count and ratios of Bifidobacterium in all bacteria were conspicuously low in the TF group as compared with the BM group. And with the change from MA-1 to MA-1[R] in the TF group, the bacterial number and the occupation ratio of Bifidobacterium were increased, and Enterobacteriaceae bacterial count and the occupation ratio were decreased. The change of the intestinal flora with MA-1[R] feeding was mainly caused by the breeding action of Raffinose on bifidobacteria. Further studies are needed from a viewpoint of clinical effectiveness about the influence of normalization of the intestinal flora for the treatment of food hypersensitivity.

Bifidobacterium↗
PubMed2004

Prediction of the development of tolerance to milk in children with cow's milk hypersensitivity.

OBJECTIVES: To investigate whether the development of tolerance to cow's milk (CM) by aged 4 years can be predicted with a skin prick test (SPT) and measurements of total or specific immunoglobulin E (IgE) in the serum, taken at the time of diagnosis of cow's milk hypersensitivity (CMH). STUDY DESIGN: Infants with immediate (n=95) or delayed (n=67) challenge reactions to CM were prospectively followed to aged 4 years. CMH status was assessed annually by CM challenges. RESULTS: By aged 2, 3, and 4 years, children with delayed reactions developed tolerance to CM faster than those with immediate reactions: 64%, 92%, and 96% versus 31%, 53%, and 63%, respectively. A wheal size of <5 mm in SPT correctly identified 83% of 124 infants who developed tolerance to CM by aged 4 years, and a wheal size of >or=5 mm in SPT correctly identified 71% of 39 infants with persistent CMH. Milk-specific IgE <2 kU/L correctly identified 82% of infants who developed tolerance to CM, and milk-specific IgE >or=2 kU/L correctly identified 71% of infants with persistent CMH. CONCLUSION: SPT and milk-specific IgE in the serum are useful prognostic indicators of the development of tolerance to CM in infants with CMH.

Animals↗
PubMedDate not supplied

Lymphocyte blastogenesis in children with cow's milk hypersensitivity after its elimination from the diet.

The relationship between ingestion of cow's milk and lymphocyte transformation in cow's milk allergic children was studied. Fifty-six children were selected. Nineteen of them suffered from cow's milk hypersensitivity (HCM); 22 were allergic to several agents except to cow's milk (HOE) and 15 normal and healthy children composed the control group (NH). Lymphoblastogenesis was measured by tritiaded thymidine uptake and the cells were cultured with plasma from the same individual. The lymphoblastogenesis was indirectly estimated by the following equation: (formula; see text) where cpm I represents lymphoblastogenesis estimulated by PHA-M and cpm E represents lymphoblastic transformation with no antigen added to the culture medium. BTI was determined before and 30 days after the elimination of cow's milk from the diet. Lymphoblastogenesis, in the samples obtained before the elimination diet, was significantly increased (BTI decreased) in HCM group but not in the others (p less than 0.01). There was no difference in the lymphoblastogenesis behaviour of the three groups after 30 days of exclusion diet. The difference between the BTI values obtained before and after the elimination cow's milk from the diet would be helpful in the early diagnosis of cow's milk allergy.

Animals↗
PubMed1983

Cows' milk hypersensitivity: immediate and delayed onset clinical patterns.

The clinical patterns of adverse reactions to cows' milk were examined in 72 children with cows' milk hypersensitivity. Two main groups were found, according to the time of onset of the adverse reaction--immediate onset, within one hour of milk ingestion and delayed onset, after one hour. Children with immediate onset reactions usually had cutaneous manifestations, positive prick tests, raised IgE values, were atopic, and the reaction was provoked by only small amounts of milk. Children with delayed onset reactions usually had gastrointestinal manifestations; negative prick tests; normal IgE values; were not atopic; had a history of vomiting, diarrhoea, and colic in the first year of life; and a larger amount of milk was needed to provoke the adverse reaction. Placing affected children into one or other category should increase the reliability of interpreting milk prick tests and clinical findings.

Animals↗
PubMed1997

The frequency of cells secreting interferon-gamma and interleukin-4, -5, and -10 in the blood and duodenal mucosa of children with cow's milk hypersensitivity.

Enzyme-linked immunoabsorbant spots (ELISPOTs) have been used to analyze the frequency of cells spontaneously secreting interferon-gamma (INF-gamma), IL-4, IL-5, or IL-10 in mononuclear cells isolated from the blood of children with cow's milk-sensitive enteropathy (CMSE), cow's milk allergy (CMA), and age-matched controls. In addition, cytokine profiles of duodenal lamina propria lymphocytes were compared in patients with CMSE and control subjects. In blood, spontaneous cytokine-secreting cells were uncommon, but there was significantly increased IFN-gamma, IL-4, IL-5, and IL-10 ELISPOTs in children with CMSE and CMA compared with control subjects. IL-4 ELISPOTs were significantly greater in the blood of children with CMA compared with those with CMSE. In the lamina propria the frequencies of spontaneous cytokine-secreting cells were high compared with that in blood. Significantly increased ELISPOTs for IFN-gamma and IL-4 were found in CMSE compared with controls. IL-5 ELISPOTs were unchanged, and IL-10 ELISPOTs were reduced in CMSE compared with controls. These results show a general enhancement of Th1 and Th2-type cytokine-secreting cells in the blood of children with cow's milk hypersensitivity, although the increased IL-4-secreting cells in blood in CMA may be of relevance in view of the fact that this disease is IgE-mediated. In the lamina propria, there is also enhancement of IFN-gamma- and IL-4-secreting cells in CMSE compared with control subjects; however, cells secreting IFN-gamma are 10 times more numerous than cells secreting IL-4, showing a dominance of Th1-type responses in both controls and CMSE patients.

Animals↗
PubMed2000

Expression of CD1d in the duodenum of patients with cow's milk hypersensitivity.

CD1 cell surface glycoproteins represent a family of non-major histocompatibility complex (MHC) encoded antigen-presenting molecules. All members of the CD1 family appear to mediate the recognition of microbial or endogenous lipid and glycolipid antigens. The recognition of CD1d by a unique subset of natural killer (NK) T cells that leads to rapid production of large amounts of both type 1 and type 2 cytokines can be augmented by some synthetic glycolipids. Because of the proposed role of such CD1d-restricted T cells in immunoregulation, we hypothesized that CD1d molecules participate in mucosal immune responses in patients with gastrointestinal symptoms owing to food hypersensitivity. Patients of that category represent a heterogeneous group in which poorly defined immunological mechanisms are believed to contribute to disease pathogenesis. The expression of CD1 in duodenal biopsy samples from six patients with verified intolerance to cow's milk and six healthy controls was studied by immunoperoxidase staining of cryostat sections using a panel of mouse monoclonal antibodies (MoAbs) specific for CD1a, b, c, and d. Large numbers of CD1d positive cells were found in the lamina propria of all the patients, both during the symptomatic and the asymptomatic periods, whereas healthy controls were virtually devoid of CD1d expression in the duodenum. The localization of CD1d positive cells corresponded to areas where B cells, plasma cells and dendritic cells (DC) were present. A positive correlation was found between the numbers of CD1d(+) and CD19(+) cells in the lamina propria. In contrast to previous reports, no CD1d expression was found on the epithelial cells. Although less numerous than CD1d(+) the CD1c(+) cells were also present in all the patients and in five out of six controls. No staining for CD1a or CD1b was detected in the duodenal biopsy samples from any of the subjects. The exclusive presence of CD1d in the duodenal lamina propria of the patients with cow's milk hypersensitivity might suggest the participation of these molecules in the pathogenesis of allergic reactions to food.

Adult↗
PubMed1990

Efficacy and safety of a soy-protein-formula for feeding babies with atopic dermatitis and cow's milk hypersensitivity.

In this paper we report 21 infants with atopic dermatitis (AD) due to cow's milk (CM) hypersensitivity in 20/21 of whom a CM-free diet using as a CM-substitute a soy-protein formula improved the skin lesions, in addition to insuring a regular growth in all infants. Only one infant failed to complete the trial due to an absolute refusal of the soy protein formula. A possible secondary sensitization to soy was found in one infant, in whom dietary therapy alone was not effective. We conclude that soy-protein formulas represent an effective CM-substitute when CM must be eliminated from the diet of an infant with AD.

Dermatitis, Atopic↗
PubMed2004

Lymphoid nodular hyperplasia and cow's milk hypersensitivity in children with chronic constipation.

OBJECTIVE: To investigate the incidence of cow's milk allergy as evidenced by milk challenge and the findings of endoscopic and immunohistochemical examinations in children with chronic and refractory constipation. STUDY DESIGN: Thirty-five study subjects (mean age, 8.3 +/- 3.3 years; range, 3-15 years; 17 girls) and 15 control subjects (mean age, 11.7 +/- 3.2 years; range, 2-15 years; 9 girls) were studied by colonoscopy and a 4-week cow's milk elimination and challenge. RESULTS: Lymphoid nodular hyperplasia was the most prominent endoscopic finding in half of the subjects (46%), mostly occurring patchily in the transverse colon. Histologic findings other than lymphoid accumulation and mildly increased density of eosinophils were few. During the milk elimination and with supportive medication, 83% of subjects remitted. Constipation and/or other gastrointestinal or skin symptoms relapsed only in one third (34%) during the cow's milk challenge, these having significantly higher densities of intraepithelial gammadelta + T cells ( P <.001) in the biopsy samples of the terminal ileum as compared with the control subjects. CONCLUSIONS: We were able to find formal evidence for the presence of cow's milk allergy in children with chronic constipation.

Adolescent↗