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1.
Precision medicine in cow's milk allergy.
D'Auria, E, Venter, C
Current opinion in allergy and clinical immunology. 2020;(3):233-241
Abstract
PURPOSE OF REVIEW The aim of this review is to describe the role of precision medicine in the diagnosis, treatment, and monitoring of cow's milk allergy. RECENT FINDINGS The development of 'omics' sciences in the field of food allergy has led to a better understanding of the allergenicity of cow's milk proteins and significant advances in the knowledge of the pathogenesis and mechanisms of cow's milk allergy. Omics-based technologies allow the practitioner to better differentiate cow's milk allergy subtypes and to predict cow's milk allergy (CMA) persistence over time. Precision medicine extends the role of the oral food challenge, to determine the individual's threshold doses, and to establish tolerance to baked milk products. Other than symptom relief, dietary strategies are currently being investigated for the potential to induce tolerance. Oral immunotherapy offers a treatment option for patients with severe and persistent IgE-mediated CMA. Individual baseline-immune profiles may be predictive of cow's milk oral immunotherapy safety and efficacy.Patient data derived from current technology, in combination with the patient's history, can be translated into treatments targeted at patient-tailored interventions. SUMMARY The identification of novel biomarkers may improve diagnostic accuracy and also predict patient responsiveness to treatments. Integration of patient data will become increasingly important as omics technologies become more widely used in the clinical setting.
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2.
Measurements of aptamer-protein binding kinetics using graphene field-effect transistors.
Wang, X, Hao, Z, Olsen, TR, Zhang, W, Lin, Q
Nanoscale. 2019;(26):12573-12581
Abstract
Quantifying interactions between biomolecules subject to various environmental conditions is essential for applications such as drug discovery and precision medicine. This paper presents an investigation of the kinetics of environmentally dependent biomolecular binding using an electrolyte-gated graphene field-effect transistor (GFET) nanosensor. In this approach, biomolecular binding occurring on and in the vicinity of a graphene surface induces a change in carrier concentration, whose resulting conductance change is measured. This allows a systematic study of the kinetic properties of the binding system. We apply this approach to the specific binding of human immunoglobulin E (IgE), an antibody involved in parasite immunity, with an aptamer at different ionic strengths (Na+ and Mg2+) and temperatures. Experimental results demonstrate increased-rate binding kinetics at higher salt-ion concentrations and temperatures. In particular, the divalent cation Mg2+ yields more pronounced changes in the conformational structure of the aptamer than the monovalent cation Na+. In addition, the dissociation of the aptamer-protein complex at room temperature is found to be characterized by large unfavorable changes in the activation enthalpy and entropy.
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3.
IgE-Mediated Food Allergy.
Anvari, S, Miller, J, Yeh, CY, Davis, CM
Clinical reviews in allergy & immunology. 2019;(2):244-260
Abstract
Food allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the immune system, causing a T helper 2 response which results in IgE binding to Fcε receptors on effector cells like mast cells and basophils. The activation of these cells causes release of histamine and other preformed mediators, and rapid symptom onset, in contrast with non-IgE-mediated food allergy which is more delayed in onset. The diagnosis of IgE-mediated food allergy requires a history of classic clinical symptoms and evidence of food-specific IgE by either skin-prick or serum-specific IgE testing. Symptoms of IgE-mediated food allergies range from mild to severe. The severity of symptoms is not predicted by the level of specific IgE or skin test wheal size, but the likelihood of symptom onset is directly related. Diagnosis is excluded when a patient can ingest the suspected food without clinical symptoms and may require an in-office oral food challenge if testing for food-specific IgE by serum or skin testing is negative or low. Anaphylaxis is the most severe form of the clinical manifestation of IgE-mediated food allergy, and injectable epinephrine is the first-line treatment. Management of food allergies requires strict avoidance measures, counseling of the family about constant vigilance, and prompt treatment of allergic reactions with emergency medications. Guidelines have changed recently to include early introduction of peanuts at 4-6 months of life. Early introduction is recommended to prevent the development of peanut allergy. Future treatments for IgE-mediated food allergy evaluated in clinical trials include epicutaneous, sublingual, and oral immunotherapy.
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4.
Current and Emerging Therapies for IgE-Mediated Food Allergy.
Pesek, RD, Jones, SM
Current allergy and asthma reports. 2016;(4):28
Abstract
Food allergies are a growing clinical problem leading to increased health care utilization and decreases in patient quality of life. Current treatment recommendations include strict dietary avoidance of the offending food as well as use of self-injectable epinephrine in case of accidental exposure with allergic reaction. Although many individuals will eventually outgrow their food allergies, a substantial number will not. Significant effort has been made to find novel treatments that protect patients from food-triggered reactions as well as to develop immune-modulating therapies that could lead to tolerance. In this review, three therapies that have shown the most promise for the treatment of food allergies are highlighted: oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy.
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5.
Administration of a probiotic with peanut oral immunotherapy: A randomized trial.
Tang, ML, Ponsonby, AL, Orsini, F, Tey, D, Robinson, M, Su, EL, Licciardi, P, Burks, W, Donath, S
The Journal of allergy and clinical immunology. 2015;(3):737-44.e8
Abstract
BACKGROUND Coadministration of a bacterial adjuvant with oral immunotherapy (OIT) has been suggested as a potential treatment for food allergy. OBJECTIVE To evaluate a combined therapy comprising a probiotic together with peanut OIT. METHODS We performed a double-blind, placebo-controlled randomized trial of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 and peanut OIT (probiotic and peanut oral immunotherapy [PPOIT]) in children (1-10 years) with peanut allergy. The primary outcome was induction of sustained unresponsiveness 2 to 5 weeks after discontinuation of treatment (referred to as possible sustained unresponsiveness). Secondary outcomes were desensitization, peanut skin prick test, and specific IgE and specific IgG4 measurements. RESULTS Sixty-two children were randomized and stratified by age (≤5 and >5 years) and peanut skin test wheal size (≤10 and >10 mm); 56 reached the trial's end. Baseline demographics were similar across groups. Possible sustained unresponsiveness was achieved in 82.1% receiving PPOIT and 3.6% receiving placebo (P < .001). Nine children need to be treated for 7 to achieve sustained unresponsiveness (number needed to treat, 1.27; 95% CI, 1.06-1.59). Of the subjects, 89.7% receiving PPOIT and 7.1% receiving placebo were desensitized (P < .001). PPOIT was associated with reduced peanut skin prick test responses and peanut-specific IgE levels and increased peanut-specific IgG4 levels (all P < .001). PPOIT-treated participants reported a greater number of adverse events, mostly with maintenance home dosing. CONCLUSION This is the first randomized placebo-controlled trial evaluating the novel coadministration of a probiotic and peanut OIT and assessing sustained unresponsiveness in children with peanut allergy. PPOIT was effective in inducing possible sustained unresponsiveness and immune changes that suggest modulation of the peanut-specific immune response. Further work is required to confirm sustained unresponsiveness after a longer period of secondary peanut elimination and to clarify the relative contributions of probiotics versus OIT.
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6.
DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection.
Everson, TM, Lyons, G, Zhang, H, Soto-Ramírez, N, Lockett, GA, Patil, VK, Merid, SK, Söderhäll, C, Melén, E, Holloway, JW, et al
Genome medicine. 2015;(1):89
Abstract
BACKGROUND The prevalence of allergic diseases are increasing worldwide, emphasizing the need to elucidate their pathogeneses. The aims of this study were to use a two-stage design to identify DNA methylation levels at cytosine-phosphate-guanine (CpG) sites across the genome associated with atopy and high serum immunoglobulin E (IgE), then to replicate our findings in an independent cohort. METHODS Atopy was assessed via skin prick tests and high serum IgE. Methylation levels were measured from whole blood using the Illumina Infinium HumanMethylation450 BeadChip from 18-year-old women (n = 245) and men (n = 122) in the Isle of Wight birth cohort. After data cleaning and processing, and removing probes with possible single nucleotide polymorphisms, DNA methylation levels from 254,460 CpG sites from the 245 women were subjected to recursive Random Forest feature selection for stage 1. The sites selected from stage 1 were tested in stage 2 for associations with atopy and high IgE levels (>200 kU/L) via logistic regression adjusted for predicted cell-type proportions and sex. Sites significantly associated with atopy in stage 2 underwent replication tests in the independent Swedish birth cohort BAMSE (n = 464). RESULTS In stage 1, 62 sites were selected, of which 22 were associated with atopy in stage 2 (P-value range 6.5E-9 to 1.4E-5) and 12 associated with high IgE levels (P-value range 1.1E-5 to 7.1E-4) at the Bonferroni adjusted alpha (0.05/62 = 0.0008). Of the 19 available sites, 13 were replicated. CONCLUSIONS We identified 13 novel epigenetic loci associated with atopy and high IgE that could serve as candidate loci for future studies; four were within genes with known roles in the immune response (cg04983687 in the body of ZFPM1, cg18219873 in the 5'UTR of PRG2, cg27469152 in the 3'UTR of EPX, and cg09332506 in the body of COPA).
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7.
[Effects of yiqi huoxue qufeng decoction on the diamine oxidase and immunoglobin E of patients with chronic urticaria].
Wu, CX, Li, N, Xu, ZH
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2012;(9):1216-8
Abstract
OBJECTIVE To observe effects of Yiqi Huoxue Qufeng Decoction (YHQD, with the actions of replenishing qi, activating blood, and dispelling wind) on diamine oxidase (DAO) and immunoglobulin E (IgE) of patients with chronic urticaria. METHODS Eighty-five chronic urticaria patients from the clinics of dermatology, Shaanxi Hospital of Traditional Chinese Medicine were randomly assigned to the treatment group (50 cases) and the control group (35 cases). Besides, another 15 healthy volunteers were recruited as the healthy group. Patients in the treatment group took YHQD, one dose daily, once in the morning and once in the evening. Patients in the control group took Fuyang Granule (FYG), 6 g each time, three times daily. The therapeutic course for the two groups was 8 weeks. The effective rates of the two groups were observed after treatment and 2 months after quitting treatment. The levels of DAO and IgE were observed in the three groups before and after treatment. RESULTS The post-treatment recovery rate (20 cases, 44.0%) and the effective rate 2 months after quitting treatment (62.0%) were higher in the treatment group than in the control group (7 cases, 20.0%; 31.4%) with statistical difference (P<0.05). The DAO level in the two treatment groups (6.9 +/- 1.8 in the treatment group and 6.5 +/- 1.8 in the control group) was obviously higher than that in the healthy group (1.1 +/- 0.4), showing statistical difference (P<0.05). The post-treatment DAO and IgE both decreased in the treatment group and the control group when compared with before treatment in the same group. Those were lower in the treatment group than in the control group with statistical difference (P<0.05). CONCLUSION YHQD could improve the symptoms of chronic urticaria patients, ameliorate the intestines mucosa barrier function and the immunity.
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8.
Non-IgE mediated food allergy - update of recent progress in mucosal immunity.
Jyonouchi, H
Inflammation & allergy drug targets. 2012;(5):382-96
Abstract
As opposed to IgE mediated food allergy (IFA) which can cause fatal outcomes, non-IgE mediated FA (NFA) was initially thought to be a benign condition mediated by cellular immune responses, primarily affecting the GI mucosa. NFA children were thought to recover well upon avoidance of offending food. Although pathogenesis of NFA is still not well understood, recent studies indicate widely variable clinical manifestations of NFA. In parallel to our better appreciation of clinical features of NFA, complex regulatory mechanisms of gut immune homeostasis have become known with progress in our understanding of the gut mucosal immune system. In addition, a role of gut commensal flora on the gut immune system has also become better understood along with the effects of dietary components. Subtle changes in interactions between environmental factors (microbiota, dietary components, etc.) and the gut immune responses can affect gut immune homeostasis, which can result in undesired adverse reactions to food proteins (FPs). This review discusses recent progress in our understanding of the regulatory mechanisms of gut immune homeostasis and recently revealed widely variable clinical presentations of NFA with respect to it pathogenesis.
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9.
Clinical presentations of food allergy.
Mansoor, DK, Sharma, HP
Pediatric clinics of North America. 2011;(2):315-26, ix
Abstract
Food allergies are immune-mediated responses to food proteins. Because of differences in the underlying immunologic mechanisms, there are varying clinical presentations of food allergy. This article discusses the manifestations of IgE-mediated disorders, including urticaria and angioedema, rhinoconjunctivitis, asthma, gastrointestinal anaphylaxis, generalized anaphylaxis, food-dependent exercise-induced anaphylaxis, and oral allergy syndrome. It also reviews the presentations of mixed IgE- and cell-mediated disorders, including atopic dermatitis and eosinophilic gastrointestinal disorders. Finally, the manifestations of cell-mediated food allergies are discussed, including dietary protein-induced proctitis and proctocolitis, food protein-induced enterocolitis syndrome, celiac disease, and food-induced pulmonary hemosiderosis.
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10.
Adverse food reactions--an emerging issue for adults.
Skypala, I
Journal of the American Dietetic Association. 2011;(12):1877-91
Abstract
Adverse reactions to foods are classified according to the presence or absence of involvement of the immune system, which may or may not include the production of immunoglobulin E (IgE) antibodies. This review focuses on the epidemiology, diagnosis, and management of adverse food reactions, primarily in adults, and excluding celiac disease and lactose intolerance. Reported reactions to foods are often believed to be manifestations of a food allergy; however, IgE-mediated food allergy only affects 1% to 4% of adults, with seafood, tree nuts, peanuts, fruits, and vegetables being the most common triggers. Diagnosis is challenging and most commonly achieved through careful evaluation of clinical history followed by elimination and reintroduction or challenge with the suspected offending food. With acute-onset allergic reactions, estimation of food-specific IgE antibodies is frequently used to confirm or refute the diagnosis. Recent developments, such as single allergen assays, enhance the diagnosis of IgE-mediated food allergy, but the gold standard remains oral food challenge. Despite recent advances in the management of food allergy, including the promotion of oral tolerance, the mainstay of management is still the avoidance of food triggers. Dietary management can be compromised by nutritional inadequacy, accidental exposure, food labeling, and quality of life or adherence issues. It is essential that adults with confirmed food allergy receive optimal nutrition and dietetic support to enable them to manage their condition.