N-Glycan Branching Is Required for Development of Mature B Cells.

Galectins have been implicated in inhibiting BCR signaling in mature B cells but promoting pre-BCR signaling during early development. Galectins bind to branched N-glycans attached to cell surface glycoproteins to control the distribution, clustering, endocytosis, and signaling of surface glycoproteins. During T cell development, N-glycan branching is required for positive selection of thymocytes, inhibiting both death by neglect and negative selection via enhanced surface retention of the CD4/CD8 coreceptors and limiting TCR clustering/signaling, respectively. The role of N-glycan branching in B cell development is unknown. In this study, we report that N-glycan branching is absolutely required for development of mature B cells in mice. Elimination of branched N-glycans in developing B cells via targeted deletion of N-acetylglucosaminyl transferase I (Mgat1) markedly reduced cellularity in the bone marrow and/or spleen and inhibited maturation of pre-, immature, and transitional stage 2 B cells. Branching deficiency markedly reduced surface expression of the pre-BCR/BCR coreceptor CD19 and promoted spontaneous death of pre-B cells and immature B cells in vitro. Death was rescued by low-dose pre-BCR/BCR stimulation but exacerbated by high-dose pre-BCR/BCR stimulation as well as antiapoptotic BclxL overexpression in pre-B cells. Branching deficiency also enhanced Nur77 induction, a marker of negative selection. Together, these data suggest that, as in T cells, N-glycan branching promotes positive selection of B cells by augmenting pre-BCR/BCR signaling via CD19 surface retention, whereas limiting negative selection from excessive BCR engagement.

Impact of food allergy on food insecurity and health literacy in a tertiary care pediatric allergy population.

BACKGROUND: Food insecurity (FI), limited availability of or access to nutritional foods, is linked to poor child/caregiver health. We examined FI in food-allergic and non-food-allergic children to determine whether dietary limitations associated with food allergy increases risk of FI. METHODS: Food-allergic and non-food-allergic children (1-17 years) were recruited from Arkansas Children's Hospital allergy/asthma clinics. The USDA Food Security Survey, the Newest Vital Sign Health Literacy (HL) questionnaire, and the Food Allergy Impact Scale QOL survey were administered. Logistic regression and analysis of covariance models were utilized for data analysis. RESULTS: Subjects (n = 650) included 325 food-allergic and 325 non-food-allergic children. Overall rate of FI was 21.5% (food allergic 22.2% and non-food allergic 20.9%) with no significant difference in the prevalence of FI between groups (OR = 1.30; 95% CI 0.86-1.96; P = 0.21). FI was increased in households of children with both milk and egg allergy when compared to those without food allergy and those with single food allergy (OR = 2.5; 95% CI 1.4-4.6; P = 0.003). Mean HL rates were higher in the food-secure vs food-insecure groups (mean diff = 0.31; 95% CI 0.03-0.59; P = 0.03). Among food-allergic children, QOL was better in the food-secure vs food-insecure group (mean diff = 0.61; 95% CI 0.002-1.23; P = 0.049). CONCLUSION: Food allergy to milk and egg was associated with increased risk of household FI. Food-insecure participants had lower HL than their food-secure counterparts. Further work is needed to define risks associated with FI among food-allergic children to improve screening and management strategies.

Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy.

BACKGROUND: Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy. OBJECTIVE: Our primary objective was to determine whether peanut OIT can induce sustained unresponsiveness after withdrawal of OIT. METHODS: We conducted a pilot clinical trial of peanut OIT at 2 US centers. Subjects age 1 to 16 years were recruited and treated for up to 5 years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg/d peanut protein. Blood was collected at multiple time points. Clinical end points were measured with 5000-mg double-blinded, placebo-controlled food challenges once specific criteria were met. RESULTS: Of the 39 subjects originally enrolled, 24 completed the protocol and had evaluable outcomes. Twelve (50%) of 24 successfully passed a challenge 1 month after stopping OIT and achieved sustained unresponsiveness. Peanut was added to the diet. At baseline and the time of challenge, such subjects had smaller skin test results, as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2 and lower ratios of peanut-specific IgE/total IgE compared with subjects not passing. There were no differences in peanut IgG4 levels or functional activity at the end of the study. CONCLUSIONS: This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated for up to 5 years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin test results and lower allergen-specific IgE levels were predictive of successful outcome.

Development and validation of educational materials for food allergy.

OBJECTIVE: To develop and validate a food allergy educational program. STUDY DESIGN: Materials developed through focus groups and parental and expert review were submitted to 60 parents of newly referred children with a prior food allergy diagnosis and an epinephrine autoinjector. The main outcome was correct demonstration of an autoinjector. RESULTS: The correct number of autoinjector activation steps increased from 3.4 to 5.95 (of 6) after training (P < .001) and was 5.47 at 1 year (P < .05). The mean score for comfort with using the autoinjector (7-point Likert scale) before the curriculum was 4.63 (somewhat comfortable) and increased to 6.23 after the intervention (P < .05) and remained elevated at 1 year (6.03). Knowledge tests (maximum 15) increased from a mean score of 9.2 to 12.4 (P < .001) at the initial visit and remained at 12.7 at 1 year. The annualized rate of allergic reactions fell from 1.77 (historical) the year prior, to 0.42 (P < .001) after the program. On a 7-point Likert scale, all satisfaction categories remained above a favorable mean score of 6: straight-forward, organized, interesting, relevant, and recommend to others. CONCLUSIONS: This food allergy educational curriculum for parents, now available online at no cost, showed high levels of satisfaction and efficacy.

Developing a food allergy curriculum for parents.

BACKGROUND: Food allergy (FA) is potentially severe and requires intensive education to master allergen avoidance and emergency care. There is evidence suggesting the need for a comprehensive curriculum for food allergic families. METHODS: This paper describes the results of focus groups conducted to guide the development of a curriculum for parents of food allergic children. The focus groups were conducted using standard methodology with experienced parents of food allergic children. RESULTS: Participants were parents (n = 36) with experience managing FA recruited from allergy clinics at two academic centers. Topics identified by parents as key for successful management included as expected: (i) early signs/symptoms, (ii) 'cross-contamination', (iii) label-reading, (iv) self-injectable epinephrine; and (v) becoming a teacher and advocate. Participants also recommended developing a 'one page-road map' to the information, and to provide the information early and be timed according to developmental stages/needs. Suggested first points for curriculum dissemination were emergency rooms, obstetrician and pediatrician offices. Participants also recommended targeting pediatricians, emergency physicians, school personnel, and the community-at-large in educational efforts. Parents often sought FA information from non-medical sources such as the Internet and support groups. These resources were also accessed to find ways to cope with stress. Paradoxically, difficulties gaining access to resources and uncertainty regarding reliability of the information added to the stress experience. DISCUSSION: Based on reports from experienced parents of food allergic children, newly diagnosed parents could benefit from a comprehensive FA management curriculum. Improving access to clear and concise educational materials would likely reduce stress/anxiety and improve quality of life.

A systematic review into the effectiveness of occupational therapy for improving function and participation in activities of everyday life in adults with a diagnosis of depression.

BACKGROUND: Depression is a common mental health disorder, the symptoms of which can disrupt functioning and lead to reduced participation in everyday activities.  Occupational therapy is routinely provided for people with such difficulties; however, the evidence underpinning this intervention for depression has yet to be systematically assessed. METHOD: A systematic review of the effectiveness of occupational therapy for people with a diagnosis of depression, using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) was undertaken. Seven databases were searched using terms for depression combined with terms associated with occupational therapy. Due to heterogeneity in study design and outcome measures, a best evidence synthesis was undertaken as an alternative to meta-analysis. RESULTS: Of 1962 articles identified, 63 full texts were assessed and six met the inclusion criteria. Studies were carried out in Canada, Germany, the Netherlands, Taiwan and the United Kingdom. There was strong evidence for the effectiveness of occupational therapy return-to-work interventions for improving depression symptomology, limited evidence for occupational therapy lifestyle interventions for reducing anxiety and suicidal ideation, and limited evidence for improving work participation.  No studies evaluated individualised client-centred occupational therapy, highlighting a gap in research. LIMITATIONS: Incomplete reporting within studies and heterogeneity prevented meta-analysis.  English language restrictions were applied. CONCLUSIONS: Whilst overall the evidence base for occupational therapy for depression is limited, strong evidence was found for the effectiveness of occupational therapy return-to-work interventions, which is important given the costs associated with mental ill-health and work absence. Further research is needed to strengthen the evidence base.

Initial Feasibility of the "Families Moving Forward Connect" Mobile Health Intervention for Caregivers of Children With Fetal Alcohol Spectrum Disorders: Mixed Method Evaluation Within a Systematic User-Centered Design Approach.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are prevalent neurodevelopmental conditions. Significant barriers prevent family access to FASD-informed care. To improve accessibility, a scalable mobile health intervention for caregivers of children with FASD is under development. The app, called Families Moving Forward (FMF) Connect, is derived from the FMF Program, a parenting intervention tailored for FASD. FMF Connect has 5 components: Learning Modules, Family Forum, Library, Notebook, and Dashboard. OBJECTIVE: This study assesses the feasibility of FMF Connect intervention prototypes. This includes examining app usage data and evaluating user experience to guide further refinements. METHODS: Two rounds of beta-testing were conducted as part of a systematic approach to the development and evaluation of FMF Connect: (1) an iOS prototype was tested with 20 caregivers of children (aged 3-17 years) with FASD and 17 providers for the first round (April-May 2019) and (2) iOS and Android prototypes were tested with 25 caregivers and 1 provider for the second round (November-December 2019). After each 6-week trial, focus groups or individual interviews were completed. Usage analytics and thematic analysis were used to address feasibility objectives. RESULTS: Across beta-test trials, 84% (38/45) of caregivers and 94% (17/18) of providers installed the FMF Connect app. Technological issues were tracked in real time with updates to address problems and expand app functionalities. On use days, caregivers averaged 20 minutes using the app; most of the time was spent watching videos in Learning Modules. Caregiver engagement with the Learning Modules varied across 5 usage pattern tiers. Overall, 67% (30/45) of caregivers posted at least once in the Family Forum. Interviews were completed by 26 caregivers and 16 providers. App evaluations generally did not differ according to usage pattern tier or demographic characteristics. Globally, app users were very positive, with 2.5 times more positive- than negative-coded segments across participants. Positive evaluations emphasized the benefits of accessible information and practical utility of the app. Informational and video content were described as especially valuable to caregivers. A number of affective and social benefits of the app were identified, aligning well with the caregivers' stated motivators for app use. Negative evaluations of user experience generally emphasized technical and navigational aspects. Refinements were made on the basis of feedback during the first beta test, which were positively received during the second round. Participants offered many valuable recommendations for continuing app refinement, which is useful in improving user experience. CONCLUSIONS: The results demonstrate that the FMF Connect intervention is acceptable and feasible for caregivers raising children with FASD. They will guide subsequent app refinement before large-scale randomized testing. This study used a systematic, user-centered design approach for app development and evaluation. The approach used here may illustrate a model that can broadly inform the development of mobile health and digital parenting interventions.

N-Glycan Branching Decouples B Cell Innate and Adaptive Immunity to Control Inflammatory Demyelination.

B cell depletion potently reduces episodes of inflammatory demyelination in multiple sclerosis (MS), predominantly through loss of innate rather than adaptive immunity. However, molecular mechanisms controlling innate versus adaptive B cell function are poorly understood. N-glycan branching, via interactions with galectins, controls endocytosis and signaling of cell surface receptors to control cell function. Here we report that N-glycan branching in B cells dose dependently reduces pro-inflammatory innate responses by titrating decreases in Toll-like receptor-4 (TLR4) and TLR2 surface expression via endocytosis. In contrast, a minimal level of N-glycan branching maximizes surface retention of the B cell receptor (BCR) and the CD19 co-receptor to promote adaptive immunity. Branched N-glycans inhibit antigen presentation by B cells to reduce T helper cell-17 (TH17)/TH1 differentiation and inflammatory demyelination in mice. Thus, N-glycan branching negatively regulates B cell innate function while promoting/maintaining adaptive immunity via BCR, providing an attractive therapeutic target for MS.

Increasing cell permeability of N-acetylglucosamine via 6-acetylation enhances capacity to suppress T-helper 1 (TH1)/TH17 responses and autoimmunity.

N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS). Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes. Activated T cells switch metabolism from oxidative phosphorylation to aerobic glycolysis and glutaminolysis. This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching. Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity. However, GlcNAc activity is limited by the lack of a cell surface transporter and requires high doses to enter cells via macropinocytosis. Here we report that GlcNAc-6-acetate is a superior pro-drug form of GlcNAc. Acetylation of amino-sugars improves cell membrane permeability, with subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway. Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity. GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.

Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation.

Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer.

Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis.

Essential biological systems employ self-correcting mechanisms to maintain cellular homeostasis. Mammalian cell function is dynamically regulated by the interaction of cell surface galectins with branched N-glycans. Here we report that N-glycan branching deficiency triggers the Golgi to generate bioequivalent N-glycans that preserve galectin-glycoprotein interactions and cellular homeostasis. Galectins bind N-acetyllactosamine (LacNAc) units within N-glycans initiated from UDP-GlcNAc by the medial-Golgi branching enzymes as well as the trans-Golgi poly-LacNAc extension enzyme ß1,3-N-acetylglucosaminyltransferase (B3GNT). Marginally reducing LacNAc content by limiting N-glycans to three branches results in T-cell hyperactivity and autoimmunity; yet further restricting branching does not produce a more hyperactive state. Rather, new poly-LacNAc extension by B3GNT maintains galectin binding and immune homeostasis. Poly-LacNAc extension is triggered by redistribution of unused UDP-GlcNAc from the medial to trans-Golgi via inter-cisternal tubules. These data demonstrate the functional equivalency of structurally dissimilar N-glycans and suggest a self-correcting feature of the Golgi that sustains cellular homeostasis.

Food allergies in children affect nutrient intake and growth.

OBJECTIVES: To identify if specific food allergies, elimination diets, or other variables associated with food allergies have an impact on the growth and nutrient intake of children with food allergies. DESIGN: Measurements of height, weight, and body mass index were used to determine potential growth problems. Estimates of energy and nutrient intakes were based on 3-day diet records. A questionnaire was used to determine number of food allergies and other variables. SUBJECTS: Ninety-eight children with food allergies (subjects, mean age 3.7 +/- 2.3 years) and 99 children without food allergies (controls, mean age 4.1 +/- 2.4 years) participated in this age-matched, consecutive sampling, cross-sectional study. STATISTICAL ANALYSIS PERFORMED: Cochran-Mantel-Haenszel statistics using general association and Fisher Exact Test, with 2-sided probability, were conducted. RESULTS: Children with two or more food allergies were shorter, based on height-for-age percentiles, than those with one food allergy (P<.05). More than 25% of children in both groups consumed less than 67% of the DRI (RDA or AI) for calcium, vitamin D, and vitamin E. More children with cow's milk allergy or multiple food allergies consumed dietary calcium less than age- and gender-specific recommendations compared with children without cow's milk allergy and/or one food allergy. The possibility of consuming a less than recommended intake of calcium and vitamin D in children with food allergy was less if the child received nutrition counseling (P<.05) or consumed a safe infant/toddler formula or fortified soy beverage. APPLICATIONS/CONCLUSIONS: Children diagnosed with food allergies need an annual nutrition assessment to prevent growth problems or inadequate nutrient intake. Children with milk allergies or multiple food allergies are at greater risk. Nutrition education needs to address how to avoid all forms of the allergen and incorporate alternative nutrient-dense foods. This population would benefit from the development and validation of a medical nutrition therapy protocol.

Phenotypic and transcriptional fidelity of patient-derived colon cancer xenografts in immune-deficient mice.

Xenografts of human colorectal cancer (CRC) in immune-deficient mice have great potential for accelerating the study of tumor biology and therapy. We evaluated xenografts established in NOD/scid/IL2Rγ-null mice from the primary or metastatic tumors of 27 patients with CRC to estimate their capacity for expanding tumor cells for in vitro studies and to assess how faithfully they recapitulated the transcriptional profile of their parental tumors. RNA-seq analysis of parental human CRC tumors and their derivative xenografts demonstrated that reproducible transcriptional changes characterize the human tumor to murine xenograft transition. In most but not all cases, the human stroma, vasculature, and hematopoietic elements were systematically replaced by murine analogues while the carcinoma component persisted. Once established as xenografts, human CRC cells that could be propagated by serial transplantation remained transcriptionally stable. Three histologically atypical xenografts, established from patients with peritoneal metastases, contained abundant human stromal elements and blood vessels in addition to human tumor cells. The transcriptomes of these mixed tumor/stromal xenografts did not closely resemble those of their parental tumors, and attempts to propagate such xenografts by serial transplantation were unsuccessful. Stable expression of numerous genes previously identified as high priority targets for immunotherapy was observed in most xenograft lineages. Aberrant expression in CRC cells of human genes that are normally only expressed in hematopoietic cells was also observed. Our results suggest that human CRC cells expanded in murine xenografts have great utility for studies of tumor immunobiology and targeted therapies such as immunotherapy but also identify potential limitations.

Food allergy educational needs of pediatric dietitians: a survey by the Consortium of Food Allergy Research.

OBJECTIVE: To determine pediatric dietitians' self-reported proficiency, educational needs, and preferences regarding food allergy (FA) management. DESIGN AND SETTING: An Internet-based, anonymous survey was distributed to the Pediatric Nutrition Practice Group (PNPG) of the American Dietetic Association. PARTICIPANTS: Respondents (n = 311) were registered dietitians and members of the PNPG. ANALYSIS: Results are presented using descriptive statistics. Chi-square tests were applied for subgroup analyses. Percentage responses were calculated per question based on the number of respondents answering the question. RESULTS: On a 4-point scale of proficiency ("high," "moderate," "low," and "none"), respondents primarily rated themselves "moderate" for educating families, creating diets, and evaluating safe food items, and "low" for creating diagnostic food challenges. Education was primarily self-taught (75%). Preferences for future resources included handbooks (77%) and Web-based instructional programs (53%). On a 4-point scale ("very" to "not at all" needed) among practices that included >10% patients with FA, ratings of "very" were defined as need resources to update FA knowledge (87%) and need for a FA "tool kit" (84%). CONCLUSIONS AND IMPLICATIONS: Pediatric dietitians manage FA for a substantial patient base although their self-reported proficiency is overall only moderate. Dietitians would prefer and likely benefit from Internet-accessible management handbooks and patient handouts.

Egg oral immunotherapy in nonanaphylactic children with egg allergy.

BACKGROUND: There is no current active treatment for food allergy. Traditional injection immunotherapy has been proved unsafe, and thus there is a need for other forms of immunotherapy. OBJECTIVE: The purpose was to study the safety and immunologic effects of egg oral immunotherapy (OIT). The short-term goal was to desensitize subjects to protect against accidental ingestion reactions. The eventual goal was to induce lasting clinical and immunologic tolerance. METHODS: Subjects with a history of egg allergy but without a history of anaphylaxis to egg underwent a 24-month egg OIT protocol involving modified rush, build-up, and maintenance phases. Double-blind, placebo-controlled food challenges were performed at study conclusion. Egg-specific IgE and IgG concentrations were followed. RESULTS: Seven subjects completed the protocol. Egg-specific IgG concentrations increased significantly, whereas egg-specific IgE concentrations did not significantly change. Three subjects tolerated known or possible accidental egg ingestions while receiving OIT. During double-blind, placebo-controlled food challenges at study conclusion, all tolerated significantly more egg protein than at study onset and than that found in the typical accidental exposure. Two subjects demonstrated oral tolerance. CONCLUSION: This study provides proof of concept that OIT can be safely used for patients with egg allergy without a history of anaphylaxis to egg. Egg OIT does not heighten sensitivity to egg and might protect against reaction on accidental ingestion. Whether OIT will induce clinical oral tolerance cannot be concluded from this initial cohort. CLINICAL IMPLICATIONS: Use of allergen-specific OIT to protect subjects with food allergy from reaction on accidental ingestion would represent a significant paradigm change in the treatment of food allergy.

Peanut allergy: recurrence and its management.

BACKGROUND: Although peanut allergy may recur, the frequency with which this occurs is unknown. OBJECTIVE: The goals of this study were to determine the rate of peanut allergy recurrence, identify risk factors for recurrent peanut allergy, and develop specific recommendations for the treatment of patients with resolved peanut allergy. METHODS: Children who outgrew peanut allergy were evaluated with questionnaires, skin tests, and peanut-specific IgE levels. Patients were invited to undergo a double-blind, placebo-controlled food challenge (DBPCFC) unless the history of a possible recurrence reaction was so convincing that a challenge would be potentially dangerous. RESULTS: Sixty-eight patients were evaluated. Forty-seven patients continued to tolerate peanut, of whom 34 ingested concentrated peanut products at least once per month and 13 ate peanut infrequently or in limited amounts but passed a DBPCFC. The status of 18 patients was indeterminate because they ate peanut infrequently or in limited amounts and declined to have a DBPCFC. After excluding 12 patients originally diagnosed with peanut allergy based solely on a positive skin prick test or peanut-specific IgE level, 3 of 15 patients who consumed peanut infrequently or in limited amounts had recurrences, compared with no recurrences in the 23 patients who ate peanut frequently ( P = .025). The recurrence rate was 7.9 (95% CI, 1.7% to 21.4%). CONCLUSION: Children who outgrow peanut allergy are at risk for recurrence, and this risk is significantly higher for patients who continue largely to avoid peanut after resolution of their allergy. On the basis of these findings, we now recommend that patients eat peanut frequently and carry epinephrine indefinitely until they have demonstrated ongoing peanut tolerance.

The natural progression of peanut allergy: Resolution and the possibility of recurrence.

BACKGROUND: It was once thought that peanut allergy is a lifelong problem. We previously reported that about 20% of children outgrow their peanut allergy and that more than 60% of patients with a peanut-IgE level of 5 or less passed an oral challenge. OBJECTIVE: The goal of this study was to further describe the natural progression of peanut allergy by reviewing patients who have undergone oral peanut challenges since the previous study. METHODS: Patients with peanut-IgE levels of 5 or less were offered a peanut challenge. Those who passed were further evaluated by questionnaire to assess reintroduction of peanut into their diet and whether any recurrence has occurred. RESULTS: Eighty-four patients were evaluated, and 80 underwent complete analysis. Fifty-five percent with peanut-IgE levels of 5 or less and 63% with peanut-IgE levels of 2 or less passed challenges, compared to 61% and 67%, respectively, in our previous study. The 4 additional patients passed peanut challenges in this study after previously failing. Three patients with initial anaphylactic reactions and 2 patients with initial peanut-IgE levels greater than 70 passed their challenge. Follow-up of those who passed in both studies showed that the majority of patients reintroduced peanut into their diet, but that continued label reading, infrequent/limited ingestion, and aversion to peanut were all common in this population. Two patients had suspected subsequent reactions to peanut after passing their challenge. CONCLUSIONS: Patients with a history of peanut allergy and peanut-IgE levels of 5 or less have at least a 50% chance of outgrowing their allergy. Recurrence of peanut allergy may occur but appears to be uncommon.

Factors affecting the determination of threshold doses for allergenic foods: how much is too much?

BACKGROUND: Ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies. The threshold dose for provocation of such reactions is often considered to be zero. However, because of various practical limitations in food production and processing, foods may occasionally contain trace residues of the offending food. Are these very low, residual quantities hazardous to allergic consumers? How much of the offending food is too much? Very little quantitative information exists to allow any risk assessments to be conducted by the food industry. OBJECTIVE: We sought to determine whether the quality and quantity of existing clinical data on threshold doses for commonly allergenic foods were sufficient to allow consensus to be reached on establishment of threshold doses for specific foods. METHODS: In September 1999, 12 clinical allergists and other interested parties were invited to participate in a roundtable conference to share existing data on threshold doses and to discuss clinical approaches that would allow the acquisition of that information. RESULTS: Considerable data were identified in clinical files relating to the threshold doses for peanut, cows' milk, and egg; limited data were available for other foods, such as fish and mustard. CONCLUSIONS: Because these data were often obtained by means of different protocols, the estimation of a threshold dose was very difficult. Development of a standardized protocol for clinical experiments to allow determination of the threshold dose is needed.