Cow's Milk Hypersensitivity Research Articles

Prevalence and risk factors for milk allergy overdiagnosis in the BEEP trial cohort.

Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual-level and primary care practice-level risk factors. We analysed data from 1394 children born in England in 2014-2016 (BEEP trial, ISRCTN21528841). Participants underwent formal CMA diagnosis at ≤2 years. CMA overdiagnosis was defined in three separate ways: parent-reported milk reaction; primary care record of milk hypersensitivity symptoms; and primary care record of low-allergy formula prescription. CMA was formally diagnosed in 19 (1.4%) participants. CMA overdiagnosis was common: 16.1% had parent-reported cow's milk hypersensitivity, 11.3% primary care recorded milk hypersensitivity and 8.7% had low-allergy formula prescription. Symptoms attributed to cow's milk hypersensitivity in participants without CMA were commonly gastrointestinal and reported from a median age of 49 days. Low-allergy formula prescriptions in participants without CMA lasted a median of 10 months (interquartile range 1, 16); the estimated volume consumed was a median of 272 litres (26, 448). Risk factors for CMA overdiagnosis were high practice-based low-allergy formula prescribing in the previous year and maternal report of antibiotic prescription during pregnancy. Exclusive formula feeding from birth was associated with increased low-allergy formula prescription. There was no evidence that practice prescribing of paediatric adrenaline auto-injectors or anti-reflux medications, or maternal features such as anxiety, age, parity and socioeconomic status were associated with CMA overdiagnosis. CMA overdiagnosis is common in early infancy. Risk factors include high primary care practice-based low-allergy formula prescribing and maternal report of antibiotic prescription during pregnancy.

A Cytologic Assay for Diagnosis of Food Hypersensitivity in Patients With Irritable Bowel Syndrome

A percentage of patients with symptoms of irritable bowel syndrome (IBS) suffer from food hypersensitivity (FH) and improve on a food-elimination diet. No assays have satisfactory levels of sensitivity for identifying patients with FH. We evaluated the efficacy of an in vitro basophil activation assay in the diagnosis of FH in IBS-like patients. Blood samples were collected from 120 consecutive patients diagnosed with IBS according to Rome II criteria. We analyzed in vitro activation of basophils by food allergens (based on levels of CD63 expression), as well as total and food-specific immunoglobulin (Ig)E levels in serum. Effects of elimination diets and double-blind food challenges were used as standards for FH diagnosis. Twenty-four of the patients (20%) had FH (cow's milk and/or wheat hypersensitivity); their symptom scores improved significantly when they were placed on an elimination diet. Patients with FH differed from other IBS patients in that they had a longer duration of clinical history, a history of FH as children, and an increased frequency of self-reported FH; they also had hypersensitivities to other antigens (eg, egg or soy). The basophil activation assay diagnosed FH with 86% sensitivity, 88% specificity, and 87% accuracy; this level of sensitivity was significantly higher than that of serum total IgE or food-specific IgE assays. A cytometric assay that quantifies basophils after stimulation with food antigens based on cell-surface expression of CD63 had high levels of sensitivity, specificity, and accuracy in diagnosing FH. This assay might be used to diagnose FH in patients with IBS-like symptoms.

Elimination and provocation test in cow's milk hypersensitive children

Background Allergic disease in infancy mostly related to cow's milk allergy. The prevalence of cow's milk hypersenstivity in chil- dren has increased steadily in the past years; therefore diagnostic accuracy is important and every symptomatic child with positive specific lgE should be followed by elimination and provocation. Objective To diagnose cow's milk hypersensitivity on children un- der three years old using elimination and provocation methods. Methods This was a clinical diagnosis study, in which children with allergy symptoms were examined for cow's milk sensitivity using prick test or lgE Radioallergosorbent test (RAST). Those with positive results underwent an elimination for minimal of 2 weeks and were challenged aterwards. The study was a qualitative diagnostic test with the gold standard of recurrence of symptoms after challenge test. Results There were forty subjects included in the challenge pro- cess with mean age of 17 months old. Boys and girls were equally distributed. There were 6 7% subjects with positive results on challenge with positive prick test and 64% positive challenge with history of positive lgE RAST. Sixty-five percents of subjects with positive results on challenge had more than 2 weeks elimination period. There was no statistical significance found in children with positive results on challenge, using neither prick test or lgE RAST. Conclusions Cow's milk protein allergy can be diagnosed on chil- dren less than 3 years old by applying elimination and challenge procedure. lgE sensitivity alone can not determine hypersensitivity

Prevalence of immediate hypersensitivity reactions to cow‘s milk in infants based on skin prick test and questionnaire

Cow's milk (CM) hypersensitivity is one of the most frequent hypersensitivities in infants. The objective of our study was to investigate the prevalence of immediate hypersensitivity to CM based on skin prick test results and to evaluate associated allergic conditions ascertained by questionnaire in infants living in Istanbul. All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on cow's milk hypersensitivity and other allergic diseases was completed during this interview. A cow's milk skin prick test (SPT) was applied to all infants. An open CM challenge test was then carried out on infants with a positive SPT to CM. Among the 1015 infants who underwent SPT, six (0.59 %) demonstrated immediate hyper-sensitivity to the CM allergen and three (0.29 %) developed a positive response to the CM challenge test. The results of the questionnaire revealed that 112 (11.0 %) of the infants had family history of allergic diseases, 96 infants (9.5 %) had a positive history of recurrent wheezing, and 166 (16.4 %) had a history of skin rash resembling atopic dermatitis. Our results suggest that CM hyper-sensitivity, with its low prevalence, might not be a serious health concern in Turkish infants.

Colonic Lymphoid Nodular Hyperplasia in Children: Relationship to Food Hypersensitivity

The clinical significance of lymphoid nodular hyperplasia (LNH) of the lower gastrointestinal tract is unclear. The aim of this study was to define the frequency and clinical significance of LNH in pediatric patients undergoing colonoscopy. Two hundred forty-five children (101 male, 144 female; median age, 8.5 years) for whom colonoscopy had been indicated were evaluated during a 3-year period. Apart from ileocolonoscopy with biopsy, all patients underwent routine biochemistry, serum total and specific IgE, and/or skin prick tests for food allergens. Patients with LNH underwent elimination diet and subsequent food challenges. LNH was observed in 73 of 245 (30%) consecutive colonoscopies. LNH was the only abnormal finding in 52 of the 73 cases (71%). In 43 of these 52 patients a diagnosis of cow's milk or multiple food hypersensitivity was made. Food allergy was significantly more common than in patients without LNH (83% vs 31%; P < .0001). The patients with LNH and food hypersensitivity presented hematochezia (P < .0001), elevated serum anti-beta-lactoglobulin IgG (P < .0001), anemia (P < .005), and failure to thrive (P < .03) more frequently than those without LNH. In the LNH patients histologic examination showed a higher number of lymphoid follicles throughout the colon and the terminal ileum and an increased number of lamina propria and intraepithelial eosinophils. The presence of LNH in the colon and/or terminal ileum is a frequent finding in symptomatic children undergoing colonoscopy. Unless associated with other specific endoscopic or histologic lesions, LNH is related to a condition of delayed-type food hypersensitivity.

A New Murine Model of beta-Lactoglobulin-Specific IgE-Mediated Cow's Milk Hypersensitivity

RATIONALE: Induction of oral tolerance and failure to induce any detectable IgE production in animals after beta-Lactoglobulin (BLG) or cow's milk (CM) feeding hinder better understanding of pathogenic mechanisms involved in cow's milk allergy (CMA). We sought to develop a murine model of BLG-specific IgE-mediated cow's milk hypersensitivity (CMH) induction by oral sensitization with CM without adjuvants.

Determination of Epitope Diversity in Cow's Milk Hypersensitivity Using Microarray Immunoassay

RATIONALE: Cow's milk hypersensitivity is a common disease affecting 2.5% children in the first year of life. Since measurement of binding to specific milk protein epitopes may be clinically useful, we sought to develop a peptide microarray immunoassay to map allergenic milk epitopes using microliter quantities of serum. METHODS: A library of peptides were synthesized commercially, which consisted of 20 amino acids overlapping by 18 (2-offset) and corresponded to the primary sequences of αs1-, αs2-, β-, and κ-caseins, and β-lactoglobulin. These peptides were arrayed in triplicate, repeated 4 times in different locations on glass substrates and used to analyze IgE- and IgG4-specific antibodies by immunolabeling with patient sera. RESULTS: Thirty-nine milk allergic patients and 10 control sera were analyzed; 21 patients had high milk-specific IgE (median milk specific IgE = >100 kIU/L, median age = 5.5 years) and 18 patients had low milk specific IgE (median milk specific IgE 0.9 kIU/L, median age = 7 years). Microarray mapping correlated well with sequential milk epitopes previously identified by SPOTs membrane technology. In addition, a greater number of peptides were recognized by those with higher milk-specific IgE levels. CONCLUSIONS: Peptide microarray immunoassay correlated with previously established allergenic milk epitopes, and allows for parallel analysis of IgE and IgG4 epitope recognition. Differences in epitope diversity may be associated with clinical features of milk hypersensitivity.

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

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. 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. 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. We were able to find formal evidence for the presence of cow's milk allergy in children with chronic constipation.

Severe Gastroesophageal Reflux Disease and Cow Milk Hypersensitivity in Infants and Children: Disease Association and Evaluation of a New Challenge Procedure

ABSTRACTBackground: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 &lt;3 years of age) or double‐blind placebo‐controlled (in patients ≥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 &gt;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.

P0483 SKIN PRICK TESTS AND RASTS IN THE DIAGNOSIS OF COW MILK ALLERGY WITH EXCLUSIVE GASTROINTESTINAL SYMPTOMS

Introduction: The provocative challenge test is still considered gold standard in the diagnosis of food hypersensitivity. However this test requires many cautions and can espose the patients (pts) to sometimes severe allergic symptoms. Therefore the diagnostic approach to food hypersensitivity could be made safe and fast by laboratory tests gifted of good predictive value in comparison with the gold standard. Aim of this retrospective study was to evaluate predictive value of skin prick tests (SPTs) and RASTs in comparison with the open challenge in the diagnosis of cow milk allergy with exclusive gastrointestinal symptoms. Methods: Ninety-six consecutive patients (pts), 41 females and 55 males, mean age 7.2 ± 2.6 years were enrolled. Inclusive criteria was: exclusive gastrointestinal symptoms (vomiting, diarrhea and abdominal pain); medical history suggestive of cow milk hypersensitivity and age more than 4 years. SPTs and RASTs for the main cow milk protein (casein, β-lactoglobulin and lattoalbumin) were performed in all pts; these pts affected by diarrhea and abdominal pain also underwent lactose breath test. All pts started a cow milk free diet and after 20 days from the beginning of the elimination diet underwent an open challenge test. A provocative test with lactose free milk was performed in all pts positive to lactose breath test. According to open challenge the pts were divided in two groups: group A (pts with positive open challenge) and group B (pts with negative open challenge). Results: GroupA (79 pts): 19 % were positive and 71 % negative to SPTs; 70% positive and 30% negative to RASTs; 4% were positive to SPTs and negative to RASTs; 58% were negative to SPTs and positive to RASTs. The number of the positive RASTs pts was significantly higher (p 0.00001) than of the positive SPTs pts. The 10 % resulted positive to lactose breath test. Group B: 6% were positive and 94 % negative to SPTs and to RASTs; 6% were positive to SPTs and negative to RASTs; 6% were negative to SPTs and positive to RASTs. The 53 % were positive to lactose breath test. Therefore the SPTs and RSTs sensitivity and specificity reached respectively 21%, 73%, 94% and 94%; the SPTs and RSTs positive and negative predictive values were respectively 28%, 57%, 91% and 97%. Conclusion: Our study shows that the RASTs are more reliable than the SPTs in the diagnosis of cow milk allergy with exclusive gastrointestinal symptoms and suggestive medical history.

Association between CD62 ligand on naïve and memory T cells and history of cow's milk hypersensitivity in atopic patients

Both IgE and non-IgE cell-mediated reactions can contribute to the immunopathogenesis of food hypersensitivity. To study L-selectin expression in naïve (CD45RA+) and memory (CD45RO+) T cells in atopic patients with a history of cow's milk allergy and CD69 expression. We evaluated 12 children with a history of cow's milk allergy. All 12 children underwent clinical history, examination, in vivo skin prick testing to inhalants and milk allergen, and in vitro radioallergosorbent testing for milk and total serum IgE levels. L-selectin levels on naive and memory T cells from patients and controls were analyzed by flow cytometry with fluorochrome-conjugated monoclonal antibodies after 4 hours or 7 days of incubation with medium alone, 1 microg/mL of pokeweed mitogen, or 50 microg/mL of casein. The percentage of CD45RA+ 62L+ cells with casein was 56% +/- 11% vs 38% +/- 7.7% in healthy controls (P < .009). The percentage of CD45RO- 62L+ cells was 22% +/- 7.1% vs 39% +/- 7.6% in healthy controls (P < .001), whereas the expression of CD62L+ in CD45RA+ and CD45RO+ cells decreased 149% +/- 33% vs 540% +/- 36% for healthy controls (P < .001) and 89% -+/- 16% vs 402% +/- 103% for healthy controls (P < .001), respectively. The results of the present study demonstrate the presence of CD62 ligand on naive and memory T cells, which might serve as a predictive marker for atopic dermatitis withother overlapping atopic disorders, such as asthma and allergic rhinitis.

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

Rationale Cow's milk hypersensitivity (CMH) is one of the most common food allergies in children. We investigated if the development of tolerance to cow's milk (CM) by the age of four can be predicted with a prick skin test (PST), and measurements of total or specific IgE in the serum, taken at the time of diagnosis of CMH. Methods Infants with immediate (n=95) or delayed (n=67) reactions to CM, which were confirmed by a double-blind placebo-controlled food challenge before the age of 1 year were prospectively followed to the age of 4. The PST (duplicate tests) with a CM based formula and the measurement of milk-specific IgE by CAP FEIA were carried out at the same time that the initial milk challenge was performed. CMH status was assessed annually by CM challenges. Results By the ages of 2, 3 and 4, children with delayed reactions developed tolerance to CM faster than those with an immediate reaction: 64%, 92% and 96% vs. 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 4 years, and ≥5 mm 71% of 39 infants with persistent CMH. Milk-specific IgE <2 kU/l correctly identified 82% of infants who developed tolerance to CM, and ≥2 kU/l 71% of infants with persistent CMH. Conclusions PST and milk-specific IgE in the serum are useful prognostic indicators of the development of tolerance to CM in infants with CMH.

Case report: An adult onset of cow's milk hypersensitive

Rationale An adverse food reaction, either due to IgE mediated or non-IgE mediated immune mechanisms consists of any abnormal reaction after the ingestion of a food. Epidermiologic data indicate that about 6% children are affected by cow's milk and other foods. However, more than 80% these individuals will eventually loose their sensitivity to those foods. Thus it is generally recognized that cow's milk hypersensitivity as an early childhood disorder. Current literature is scarce on adult onset cow's milk related adverse reactions. Methods A 17 year-old female was treated at emergency department for recent onset of recurrent wheezes, cough, hoarseness and rhinorrea after cow's milk ingestion. No cutaneous or cardiovascular complications. She had no history of other associated atopy risk factors. Results The patient was positive with prick skin test (SPT) and class 3 IgE antibody toward cow's milk. Since elimination of cow's milk from her diet, patient had not experience any symptoms. Conclusions Due to the extreme reactivity to SPT and positive IgE antibody toward cow's milk, no double blind, placebo-controlled food challenge (DBPCFC) undertaken on the patient. DBPCFC is contraindicated for patient had severe anaphylactic reactions to the suspected food. Currently, either SPTs or radioallergosorbent studies might be used first for the diagnostic will rely on a positive test result in conjunction with a suggestive history. This experience suggests adult onset cow's milk hypersensitivity will be not easily recognized. Thus, more scientific knowledge on understanding of the disorder pathogenesis, diagnostic technique and therapy are needed.

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 ≥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 ≥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.

Which Children Outgrow Milk Allergy

About 2% to 3% of infants have cow's milk hypersensitivity (CMH), but most children outgrow it by age 3. Researchers in Finland examined whether tests taken in infancy could predict which children would become tolerant to milk by age 4. Among 162 infants who were diagnosed with CMH based on …

Natural course of cow's milk allergy in childhood atopic eczema/dermatitis syndrome

This review was undertaken to determine the role of adverse reactions to bovine proteins in atopic dermatitis, recently called atopic eczema/dermatitis syndrome (AEDS). A PubMed literature search was conducted with use of the following phrases: atopic dermatitis and food allergy, atopic dermatitis and cow's milk, and cow's milk and eczema. The authors' judgment and personal interest guided the literature selection. Food allergy has a role in at least 20% of the cases of AEDS in children younger than 4 years. Cow's milk is usually the first food given to an infant, and cow's milk hypersensitivity is often the first symptom of an atopic condition. Adverse reactions to cow's milk proteins are usually categorized as immunoglobulin (Ig)E-mediated or non-IgE-mediated cow's milk allergy and nonallergic hypersensitivity (intolerance); the symptoms do not allow differentiation of these entities. In patients with cow's milk allergy and AEDS, resolution occurs in 90% by the age of 4 years. Non-IgE-mediated cow's milk allergy often disappears before the age of 1 year. Associated reactions to other foods develop in approximately 45% of patients. Allergy to potential environmental inhalant allergens has been reported in up to 28% of patients by 3 years of age and up to 80% before puberty. After consumption of large amounts of cow's milk, 45% of 10-year-old children who had become tolerant of cow's milk, but also 15% of control subjects, still had gastrointestinal complaints. The presence of cow's milk allergy during infancy increases the risks for development of other food allergies, respiratory atopy, and persistence of AEDS. Adverse reactions to bovine proteins have an important role in AEDS.

Determination of allergenicity to three cow's milk hydrolysates and an amino acid-derived formula in children with cow's milk allergy.

Products based on hydrolysed cow milk proteins or amino acid mixtures are recommended in children with cow's milk hypersensitivity. However, some children who are allergic to cow's milk and who clinically react to substitute milk formulas have been observed. To determine the tolerance and allergenicity of protein hydrolysate or amino acid-derived formulas in children with IgE-mediated cow's milk allergy. Twenty children with positive cow's milk challenges, positive skin prick tests and/or serum-specific IgE antibodies to cow's milk were selected. Oral challenges, skin prick tests and serum-specific IgE antibodies to extensively hydrolysed whey formula, partially hydrolysed whey formula, extensively hydrolysed casein formula and amino acid-derived formula were performed. Five out of 17 (5/17) children reacted to partially hydrolysed whey formula, (3/16) to extensively hydrolysed whey formula, (2/10) to amino acid-derived formula, (1/16) to extensively hydrolysed casein formula. Only extensively hydrolysed casein formula was tolerated by at least 90% (with 95% confidence intervals) of children. Hydrolysates provoked early and delayed clinical reactions, amino acid mixtures only delayed reactions. Partially hydrolysed whey formula elicited a significantly higher number of positive skin prick test reactions than other formulas. Two children had specific IgE antibodies to extensively hydrolysed whey formula, one to partially hydrolysed whey formula, one to extensively hydrolysed casein formula and none to amino acid-derived formula. In this study, none of the cow's milk substitutes has been found to be non-allergenic. Our results suggest that in children with IgE-mediated cow's milk allergy, the first ingestions of extensively hydrolysed cow's milk protein formulas require strict medical supervision because of immediate reactions. This is not the case for amino acid-derived formula. Moreover, our data suggest that treatment of children allergic to cow's milk with cow's milk substitutes should be monitored for several days to document tolerance.

Genetic susceptibility and other factors influencing the induction of cow's milk hypersensitivity

Genetic susceptibility and other factors influencing the induction of cow's milk hypersensitivity

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.

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.