IgE-mediated Cow's Milk Allergy Research Articles

Risk factors for reduced bone mineral density measurements in milk-allergic patients.

Earlier studies noted that young adults with IgE-mediated cow's milk allergy (IgE-CMA) have significantly lower bone mineral density (BMD) than age- and gender-matched controls. We sought to identify additional risk factors contributing to the low BMD in IgE-CMA patients. Postpubertal (defined by Tanner stage V) IgE-CMA patients (n=78; 16- to 30-year-old females and 17.5- to 30-year-old males) were evaluated prospectively for BMD using a DXA scan, serum values of bone turnover factor, and dietary and lifestyle questionnaires. Patients receiving>2 short courses of systemic steroid treatments were excluded. Abnormal BMD measurements (T- or Z-scores<-1.0) of the lumbar vertebrae, femoral neck, or hip were noted in 60 patients, while normal BMD values were present in 18 patients, despite similarly decreased calcium intakes between the groups (P=0.92). Patients with abnormal BMD were more likely to be asthmatic (P=0.014), have a lower weight z-score (P=0.007), have a decreased percent caloric intake derived from fat (P=0.01), and have an increased carbohydrate intake (P=0.03), in comparison with the normal-BMD group. Serum values of bone turnover were similar between the groups. On multivariate regression analysis, only asthma significantly (P=0.006) increased the risk for osteopenia and osteoporosis (OR 38.5, 95% CI 2.8-500). Fitting continuous z-scores into a regression model, both asthma and weight z-score were significant (adjusted r2 =0.272). Asthma was significantly overrepresented in osteopenic and osteoporotic subpopulations while decreased weight only in patients with osteoporosis. In the context of a low calcium intake, asthma and weight are independent risk factors for decreased BMD in IgE-CMA patients.

Early risk factors for cow's milk allergy in children in the first year of life.

Background: Cow's milk allergy (CMA) is a key form of food allergy (FA). It was shown that the frequency of FA seems to have increased during the past 10-20 years, which led to the thought that FA may have different risk factors. Epigenetic regulations and environmental pre- and postnatal factors play a large role in contributing to allergy. Understanding the risk factors that pertain to the development of FA may help to provide reasonable recommendations for prevention of the disease. Objective: To assess the impact of perinatal and environmental risk factors on the incidence of CMA in children in the first year of life. Methods: The study group consisted of 138 infants with CMA and 101 healthy infants without allergy. CMA was confirmed by an elimination test and oral food challenge. To assess infant, parental, and environmental risk factors, we used a validated questionnaire survey. Results: The incidence of CMA was three times higher in infants with a positive family history for allergy (p < 0.001). An analysis revealed that mothers of children with CMA were fourfold more frequently university educated than mothers of children without allergy (p < 0.0001). The ages of the mothers from the study group were significantly higher than the ages of the mothers from the control group. Children from the study group were breast-fed for a significantly shorter time than children from the control group. The risk of CMA was threefold lower in children who had pets at home (p = 0.0002). The risk of IgE-mediated CMA was twofold higher than the risk of non-IgE-mediated CMA if the family had more children (p = 0.04) and as many as ninefold higher if multiorgan symptoms were detected (p = 0.01). Conclusion: A positive family history of allergy and mother's education increased the risk of CMA in children in the first year of life, whereas having pets at home and a longer period of breast-feeding decreased the risk.

Consumption of soy-based infant formula is not associated with early onset of puberty.

The use of soy products is common in young children with cow milk allergy (CMA). The aim was to examine prospectively the association between infantile consumption of soy-based formula, growth parameters and early pubertal signs, in comparison to cow milk-based formula. A nested case-control study was conducted, selected from a cohort of infants prospectively followed from birth until the age of 3years for eating habits and the development of IgE-mediated CMA. Infants who consumed only soy-based formula were included in the soy group. The control group was randomly selected from those without IgE-CMA and not receiving soy formula. Study participants were reevaluated between ages 7.8 and 10.5years by an interview, nutritional intake by 3days diaries, and height, weight, and pubertal signs by physical examination. The soy-fed group included 29 participants (17 males), median age 8.92years IQR (8.21, 9.42). The control group included 60 participants (27 males), median age 8.99years IQR (8.35, 9.42). The groups had comparable height and BMI z scores (- 0.17 ± 1.08 versus - 0.16 ± 1.01, p = 0.96, and 0.67 ± 1.01 versus 0.53 ± 1.02, p = 0.56, for soy and control groups, respectively). Four (three males and one female) from the soy-group (13.8%) and eight females from the control-group (13.3%) had early pubertal signs (p = 0.95). No association was detected between puberty and infantile nutrition, after controlling for BMI and family data. No association with puberty or differences between groups were found in current daily consumption of soy, micronutrients, energy, carbohydrates, fat, and protein. This is the first prospective, physical examination-based study, demonstrating no association between infantile soy-based formula consumption and growth and puberty parameters.

Altered miR-193a-5p expression in children with cow's milk allergy.

Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We have shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls. Peripheral blood mononuclear cells were obtained from children aged 4-18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next-generation sequencing-based approach. Functional assessment of IL-4 expression was also performed. Among the miRNAs differently expressed, 2 were upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a-5 inhibitor showed a significant upregulation of IL-4 mRNA and its protein expression. Children who outgrew CMA showed miRNA-193a-5p level, and its related targets expression, similar to that observed in healthy controls. Our results suggest that miR-193a-5p is a post-transcriptional regulator of IL-4 expression and could have a role in IgE-mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.

Natural history of immunoglobulin E-mediated cow's milk allergy in a population of Argentine children.

Cow's milk protein allergy is the most common allergy in pediatrics. Immunoglobulin E (IgE)-mediated cow's milk allergy poses a higher risk for life and a worse prognosis. To describe the course of IgE-mediated cow's milk protein allergy and risk factors associated with disease persistence. This was a descriptive, retrospective study conducted in patients seen at the Division of Pediatric Allergy of Hospital Italiano between June 2006 and June 2012 who had been diagnosed with IgE-mediated cow's milk allergy. Out of the 72 patients with IgE-mediated cow's milk allergy, 39 (54%) were boys. Patients' average age at the time of diagnosis was 5.19 ± 3.7months old; the most common symptoms were urticaria and vomiting. Rhinitis and asthma were the most commonly observed concomitant atopic diseases. In the study period, 54.5% of patients developed tolerance at an average age of 32 months old. An 8-mm papule in the skin prick test and casein sensitization were associated with disease persistence. Overall, 54.5% of patients developed tolerance at 32 months old. A significant association was observed between papule size at the time of diagnosis and casein sensitization and disease persistence.

Tolerance to baked and fermented cow's milk in children with IgE-mediated and non-IgE-mediated cow's milk allergy in patients under two years of age

BackgroundIgE-mediated cow's milk allergy (CMA) has been shown consistent in milder heated-milk tolerant and severe heated-milk reactant groups in patients older than two years. Little is known whether fermentation of milk gives rise to similar clinical phenotypes.We aimed to determine the influence of extensively heated and fermented cow's milk on the IgE-mediated and non-IgE-mediated CMA in children younger than two years. MethodsSubjects followed with the diagnosis of IgE-mediated and non-IgE-mediated CMA for at least six months underwent unheated milk challenge. IgE-mediated and non-IgE-mediated groups were categorised as unheated milk-reactive and tolerant, separately. Unheated milk-reactive groups were further challenged sequentially with fermented milk (yoghurt) and baked milk, 15 days apart. Allergy evaluation with skin tests, prick-to-prick tests and atopy patch tests were performed. ResultsFifty-seven children (median age: 14 months; range: 7–24 months) underwent unheated milk challenge. Eleven of 27 children with IgE-mediated CMA and 14 of 30 children with non-IgE-mediated CMA tolerated unheated milk. Among subjects who reacted to unheated milk; 15 of 16 subjects (93%) with IgE-mediated CMA also reacted to yoghurt, whereas 11 of 16 subjects (68%) with non-IgE-mediated CMA tolerated fermented milk. Thirteen subjects (81%) of the unheated milk-reactive IgE-mediated group tolerated to heated milk. None of 16 subjects of unheated milk-reactive non-IgE-mediated group reacted to baked milk. ConclusionThe majority of children under the age of two years with both IgE-mediated and non-IgE-mediated CMA tolerated baked-milk products. Yoghurt was tolerated in two thirds of unheated milk reactive patients suffering from non-IgE-mediated CMA.

Component-resolved diagnostics in Thai children with cow's milk and egg allergy.

Component-resolved diagnostics (CRD) have garnered a lot of attention in recent years in the diagnosis of food allergies. We aimed to investigate sensitization against cow's milk and egg white components, and to study the clinical usefulness of serum food-specific immunoglobulin E (sIgE) to cow's milk and egg white components in Thai children with cow's milk and egg allergies. Children with IgE-mediated cow's milk and/or egg allergy were enrolled. Clinical reactions were determined. Specific IgE against cow's milk, egg white, alpha-lactalbumin (ALA), beta-lactoglobulin (BLG), casein, ovomucoid, ovalbumin and conalbumin were measured. Thirteen cow's milk allergic subjects and 32 egg allergic subjects were identified. The sensitization rate to BLG and casein was 91.7%, followed by ALA (66.7%) for cow's milk, and the sensitization rate to ovalbumin was 93.8%, followed by ovomucoid (81.3%) and conalbumin (37.5%) for egg. Patients in the urticaria group had a higher level of casein sIgE than the atopic dermatitis (AD) group but this difference was not significant (9.8 kUA/L vs. 0.9 kUA/L, p = 0.11). The level of ovomucoid sIgE was significantly higher in the non-AD group than in the AD group (3.8 kUA/L vs. 1.3 kUA/L, p = 0.048). BLG and casein for cow's milk and ovomucoid and ovalbumin for egg were the common components causing sensitization in cow's milk and egg allergic patients. Among the patients with cow's milk allergy, the level of casein sIgE in the urticaria group tended to be higher than the AD group, and in egg allergic patients, the non-AD group had a significantly higher ovomucoid sIgE level compared with the AD group.

Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial

Children with cow's milk allergy (CMA) have an increased risk of other allergic manifestations (AMs). We performed a parallel-arm randomized controlled trial to test whether administration of an extensively hydrolyzed casein formula (EHCF) containing the probiotic Lactobacillus rhamnosus GG (LGG) can reduce the occurrence of other AMs in children with CMA. Children with IgE-mediated CMA were randomly allocated to the EHCF or EHCF+LGG groups and followed for 36months. The main outcome was occurrence of at least 1 AM (eczema, urticaria, asthma, and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, which was defined as the negativization of a double-blind food challenge results at 12, 24, and 36months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12months. A total of 220 children (147 boys [67%]) with a median age of 5.0months (interquartile range, 3.0-8.0months) were randomized; 110 children were placed in the EHCF group, and 110 children were placed in the EHCF+LGG group. In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36months was -0.23 (95% CI, -0.36 to -0.10; P<.001), and the absolute risk difference for the acquisition of cow's milk tolerance was 0.20 (95% CI, 0.05-0.35; P<.01) at 12months, 0.24 (95% CI, 0.08-0.41; P<.01) at 24months, and 0.27 (95% CI, 0.11-0.43; P<.001) at 36months. In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children. EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE-mediated CMA.

Effects of different dietary strategies on epigenetic mechanisms in children with IgE-mediated cow's milk allergy

Effects of different dietary strategies on epigenetic mechanisms in children with IgE-mediated cow's milk allergy

Oral Food Desensitization in Children With IgE-Mediated Cow's Milk Allergy: Immunological Changes Underlying Desensitization.

PurposeThis study aimed to evaluate the safety and efficacy to induce clinical desensitization to cow's milk (CM) of an oral immunotherapy (OIT) protocol in a pediatric population with cow's milk allergy (CMA). In addition, the immune responses against β-casein, of peripheral blood mononuclear cells (PBMCs) from CMA patients, before and after the protocol were evaluated and compared to a nonallergic population.MethodsA group of 20 children with IgE-mediated CMA and 15 nonallergic children were recruited. Allergic subjects underwent an OIT protocol based on weekly doses of commercial semi-skimmed ultra-high temperature treated (UHT) CM, followed by a maintenance phase. Immune profiles and changes in all subjects were investigated by measuring Th1, Th2, and Treg cytokines, transcription factors, and specific IgE and IgG4 levels.ResultsThe CM-OIT protocol enabled to desensitize 70% of the allergic patients. Successful OIT was accompanied by significant increases in casein-specific IgG4 levels, together with a reduction in the concentration of antigen-specific IgE and in IL-5, IL-13, and IL-10 production by β-casein-stimulated PBMCs. Baseline significant differences observed between allergic and nonallergic children in IL-13 and IL-5 levels were no longer found once the protocol had finished.ConclusionsThe OIT protocol was safe and effective in inducing milk desensitization in 70% of the children with CMA, leading to alterations in their immune profiles toward a nonallergic phenotype.

Matrix effect on baked milk tolerance in children with IgE cow milk allergy

BackgroundChildren with IgE-mediated cow's milk allergy (IgE-CMA) often tolerate baked milk within a wheat matrix. In our study we evaluated the impact of wheat matrix and of little standardised cooking procedures on tolerance of baked milk. We also tested tolerance versus parmigiano reggiano (PR) and whey-based partially hydrolysed formula (pHF). MethodsForty-eight children with IgE-CMA were enrolled. They underwent prick-by-prick (PbP) and open oral food challenge (OFC) with baked cow's milk (CM), both within a wheat matrix (an Italian cake named ciambellone) and without (in a liquid form), with PR and with pHF. After a passed OFC, children continued to eat the food tolerated. In particular, after passed OFC with ciambellone, children were allowed to eat any food containing CM within a wheat matrix, with the only condition that it was baked at 180°C for at least 30min. Three months after, parents were asked to answer a survey. Results81% of children tolerated ciambellone, 56% liquid baked CM, 78% PR and 82% pHF. Negative predictive value of PbP performed with tested foods was 100%. No IgE-mediated adverse reactions were detected at follow-up carried out by the survey. ConclusionsWheat matrix effect on tolerance of baked milk was relevant in slightly less than half of cases. If our results are confirmed by larger studies, a negative PbP will allow patients to eat processed CM without undergoing OFC. Moreover, in order to guarantee tolerance towards baked milk, strict standardised cooking procedures do not seem to be necessary.

Humoral and cellular responses to casein in patients with food protein–induced enterocolitis to cow's milk

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy manifesting within 1 to 4hours of food ingestion with repetitive emesis and lethargy. We sought to characterize immune responses to casein in children with FPIES caused by cow's milk (CM). Total IgE and IgM, CM-specific IgG, and casein-specific IgE, IgG, IgG4, and IgM levels, as well as immunoglobulin free light chains, were measured in both patients with active and those with resolved CM-FPIES. Proliferating casein/T-effector cell counts were measured in children with CM-FPIES, children with IgE-mediated CM allergy, and those tolerating CM. Cytokine concentrations in the supernatants were quantified. Serum cytokine and tryptase levels were measured before and after a positive oral food challenge (OFC) result and compared with levels in those with a negative OFC result. We found low levels of CM and casein-specific IgG and casein-specific IgG4 in patients with CM-FPIES versus those tolerating CM (P<.05). Although we found both a high CD4+ Tcell-proliferative response and TH2 cytokines production after casein stimulation in children with CM-FPIES, results were similar to those in control subjects. Significantly lower secretion of IL-10 and higher secretion of IL-9 by casein-stimulated Tcells were found in patients with CM-FPIES versus those with IgE-mediated CM allergy. Lower baseline serum levels of IL-10 and higher tryptase levels were found in active CM-FPIES versus resolved CM-FPIES. We found a significant increase in serum IL-10 and IL-8 levels after a positive OFC result. We confirm the paucity of humoral response in patients with CM-FPIES. IL-10 might play a key role in acquisition of tolerance in patients with CM-FPIES. Increased serum IL-8 levels in patients with active FPIES suggest neutrophil involvement. Elevated baseline serum tryptase levels in patients with active FPIES suggest low-grade intestinal mast cell activation or increased mast cell load.

The Association of the Delayed Introduction of Cow's Milk with IgE-Mediated Cow's Milk Allergies

Although exclusive breastfeeding at least 4 to 6 months has been recommended to prevent IgE-mediated cow's milk allergy (IgE-CMA), early introduction of food allergens has received a lot of attention in recent years for the prevention of food allergies. We aimed to determine whether IgE-CMA is associated with a feeding pattern in early infancy. In a case-control study, we retrospectively compared the patient background, past history of atopic dermatitis, bronchial asthma, family history of allergic diseases, feeding patterns in early infancy, and the reason for choosing early infancy feeding patterns of patients with IgE-CMA with age- and sex-matched healthy controls using a questionnaire completed by their mothers. To minimize the influence of confounders, we also compared patients with IgE-CMA with those with IgE-mediated egg allergy (IgE-EA). A total of 51 patients with IgE-CMA were compared with 102 controls (1:2 matching) and 32 unmatched patients with IgE-EA. In a multivariable logistic regression analysis, the adjusted odds ratio of delayed (started more than 1 month after birth) or no regular cow's milk formula (less than once daily) was 23.74 (95% CI, 5.39-104.52) comparing the CMA group with the Control group, and 10.16 (95% CI, 2.48-41.64) comparing the CMA group with the EA group. Only 3 (6.5%), 2 (4.8%), and 3 (14.3%) mothers in the CMA group, the Control group, and the EA group chose "To prevent allergic disease" as a reason for choosing exclusive or almost exclusive breastfeeding in the first month of life, respectively. The early introduction of cow's milk formula is associated with lower incidence of IgE-CMA.

Assessment of IgE and IgG4 Binding Capacities of Cow's Milk Proteins Selectively Altered by Proteases.

Specific IgE and IgG4 have been reported to play key roles in the context of IgE-mediated cow's milk allergy (CMA), but the persistence of their epitopes in milk hydrolysates has not been evaluated. Using sera from 32 CMA patients, 6 CMA patients treated by epicutaneous therapy (CM-treated), and 4 CM-tolerant peanut allergic patients, we analyzed the IgE and IgG4 binding capacities related to major milk allergens in processed milk. Different proteases (plasmin, chymosin, α-chymotrypsin, or pepsin) were used progressively and selectively to hydrolyze β-lactoglobulin (β-LG) and casein (CN) in milk. We then showed that proteases differentially affect IgE or IgG4 immunoreactivities of CN and β-LG and also that we could not relate IgE and/or IgG4 levels or specificities to milk hydrolysates to the clinical status of the patients.

Safety of Viaskin Milk Epicutaneous Immunotherapy (EPIT) in IgE-Mediated Cow's Milk Allergy (CMA) in Children (MILES Study)

Safety of Viaskin Milk Epicutaneous Immunotherapy (EPIT) in IgE-Mediated Cow's Milk Allergy (CMA) in Children (MILES Study)

Multiple food protein intolerance of infancy or severe spectrum of non—IgE-mediated cow's milk allergy?—A case series

Multiple food protein intolerance of infancy or severe spectrum of non—IgE-mediated cow's milk allergy?—A case series

Antibody-independent identification of bovine milk-derived peptides in breast-milk.

Exclusively breast-fed infants can exhibit clear signs of IgE or non IgE-mediated cow's milk allergy. However, the definite characterization of dietary cow's milk proteins (CMP) that survive the maternal digestive tract to be absorbed into the bloodstream and secreted into breast milk remains missing. Herein, we aimed at assessing possible CMP-derived peptides in breast milk. Using high performance liquid chromatography (HPLC)-high resolution mass spectrometry (MS), we compared the peptide fraction of breast milk from 12 donors, among which 6 drank a cup of milk daily and 6 were on a strict dairy-free diet. We identified two bovine β-lactoglobulin (β-Lg, 2 out 6 samples) and one αs1-casein (1 out 6 samples) fragments in breast milk from mothers receiving a cup of bovine milk daily. These CMP-derived fragments, namely β-Lg (f42-54), (f42-57) and αs1-casein (f180-197), were absent in milk from mothers on dairy-free diet. In contrast, neither intact nor hydrolyzed β-Lg was detected by western blot and competitive ELISA in any breast milk sample. Eight additional bovine milk-derived peptides identified by software-assisted MS were most likely false positive. The results of this study demonstrate that CMP-derived peptides rather than intact CMP may sensitize or elicit allergic responses in the neonate through mother's milk. Immunologically active peptides from the maternal diet could be involved in priming the newborn's immune system, driving a tolerogenic response.

Food Allergy in childhood: phenotypes, prevention and treatment

The prevalence of food allergy in childhood increased in the last decades, especially in Westernized countries where this phenomenon has been indicated as a second wave of the allergic epidemic. In parallel, scientific interest also increased with the effort to explain the reasons of this sudden rise and to identify potential protective and risk factors. A great attention has been focused on early exposures to allergenic foods, as well as on other nutritional factors or supplements that may influence the immune system in a positive direction. Both interventions on maternal diet before birth or during breastfeeding and then directly on infant nutrition have been investigated. Furthermore, the natural history of food allergy also seems to be changing over time; IgE-mediated cow's milk allergy and egg allergy seem to be more frequently a persistent rather than a transient disease in childhood, as described in the last years. Food avoidance and the emergency drugs in case of an adverse event, such as epinephrine self-injector, are currently the first-line treatment in patients with food allergies, with a resulting impairment in the quality of life and social behaviour. During the last decade, oral immunotherapy emerged as an optional treatment with remarkable results, offering a novel perspective in the treatment for and management of food allergy.

Epigenetic mechanisms elicited by butyrate in peripheral blood mononuclear cells from children with IGE-mediated cow milk allergy

L. Paparo1,∗, R. Nocerino1, R. Aitoro1, V. Granata1, L. Cosenza1, I. Langella1, A. Amoroso1, G. Gioielli 1, R. Berni Canani2 1 Department of Translational Medical Science, University of Naples “Federico II”, Naples, Italy 2 Department of Translational Medical Science and European Laboratory for the Investigation of Food-Induced Diseases and CEINGE Advanced Biotechnologies, University of Naples “Federico II”, Naples, Italy

Efficacy of baked milk oral immunotherapy in baked milk–reactive allergic patients

Patients with IgE-mediated cow's milk allergy who are nonreactive to baked milk (BM) can be desensitized with BM to promote tolerance to unheated milk (UM). We sought to test whether patients who are BM reactive can progress in BM oral immunotherapy (OIT) and become desensitized to UM as well. Fifteen patients (>4 years) who previously failed to complete our milk OIT program were enrolled into the BM OIT protocol. A dose of BM (180 °C for 30 minutes) which was less than the eliciting dose was increased 50% monthly while under medical supervision until the primary outcome dose of 1.3 g/d BM protein was achieved. Basophil reactivity and milk protein-specific IgE binding were analyzed at the first round of BM OIT therapy (T0) and at 12 months of BM treatment. In terms of the primary outcome, only 3 (21%) of 14 patients tolerated the 1.3 g/d BM dose. Although some patients initially progressed in BM OIT, 8 of 11 failed because of IgE-mediated reactions. Three did not complete the program because of non-IgE-mediated factors. An increase in challenge threshold to UM was noted in patients continuing until 12 months (P = .003), including those among whom reactions precluded continuation in the program. Patients (n = 3) who successfully reached maintenance had decreased milk-specific IgE reactivity. Furthermore, the mean difference at T0 between induced HM and UM percentages of CD203c expression was significantly lower in patients who successfully completed BM OIT than in those who did not (-11% vs 4.4%, P = .0002), which is consistent with their decreased clinical reactivity to BM. Although use of hypoallergenic BM in OIT is a promising therapy, care must be taken before its administration in BM-reactive patients because of the risk for anaphylaxis and only limited increase in challenge threshold attained.