Therapies For Food Allergy Research Articles

Investigation of Mal d 1 Allelic Variants and Phylogenetic Diversity in Contemporary and Historical Polish Apple Cultivars

Allergy is considered as the most common health problem of XXI century. Apple allergenicity is of great importance and at present the only therapy for food allergy is avoidance. Fruits are important components of a healthy diet, and therefore complete avoidance of apple and related fruits like pear, peach, and cherry can have a significant negative impact since deprives the patient’s diet from important sources of vitamins, minerals and fibers. In order to provide a contribution towards a better understanding of the genetics of the family of Mal d 1 gene, the major apple allergen, and to establish the basis for further research on allelic diversity among cultivars in relation to variation in allergenicity we evaluated Mal d 1 gene variability in contemporary and historical Polish apple cultivars (Malus × domestica Borkh.). We identified new Mal d 1 alleles and further assessed phylogenetic distance between Mal d 1 variants and antigens derived from other food sources. We also predicted possible cross-reactions between allergens originated from Malus x domestica and other plant taxa as well as showed potential binding sites of apple allergens to the antibody. Thanks to multiple sequence alignment of the amino acid sequences limited to residues which serve as interaction partners for the antibody we were able to more precisely establish phylogenetic distance between analyzed antigens in regards to the antigen epitope residues.

New developments in immunotherapies for food allergy.

Food allergy affects around 10% of the population. As the prevalence of food allergy continues to increase, disproportionately in children, new therapies for food allergy are being investigated. While there are no approved treatments for food allergy, immunotherapy facilitates significant desensitization and protection from accidental exposure. Nevertheless, current immunotherapies do not entirely nor permanently eliminate sensitivity to the food allergen. Since the rates of sustained unresponsiveness are significantly lower than desensitization, future therapies that enhance the rates of long-term tolerance in patients will catalyze progress in this field over the next 5-10 years.

Causes of Allergies and Diagnosis and Treatment

Allergies are diseases of the immune system that cause an overreaction to substances called "allergens." Allergies are grouped by the kind of trigger, time of year or where symptoms appear on the body: indoor and outdoor allergies (also called "hay fever," "seasonal," "perennial" or "nasal" allergies), food allergies, latex allergies, insect allergies, skin allergies and eye allergies. People who have allergies can live healthy and active lives. The search strategy has been devised on ovid medline and then adapted for the other databases (see Additional file 1 for full search strategies). In all cases the databases will be searched from 1 January 2000 to 30 September 2012, and limited to Europe based on the definition provided by the Organization for Economic Cooperation and Development (OECD).The resulting quality assessment scores are given alongside other study parameters in three tables. We assessed the systematic reviews based on the type of intervention or subject assessed for the prevention of food allergy or food sensitization. In this overview of systematic reviews concerning the etiology and prevention of food allergy, we identified 14 eligible publications. This systematic review will provide the most up to date estimates of the frequency of food allergy in Europe. Given the presumed increase in IgE mediated food allergy in the recent past, there is much interest in identifying the causes of food allergy and primary preventive strategies. These advances are creating the opportunities for novel therapies for food allergy. However, at the current time, the only treatment is avoidance.DOI: http://dx.doi.org/10.3126/ijls.v9i5.12701

Bacillus subtilis exopolysaccharide suppresses mast cell responses (MUC9P.754)

Abstract Commensal bacteria are being studied for their probiotic, or beneficial effects in a number of diseases. Probiotics have been proposed as a therapy for food allergy but the mechanism and efficacy of how probiotics may be preventing disease are not understood. We previously showed that we can limit diarrheal disease caused by the enteric pathogen Citrobacter rodentium using the probiotic Bacillus subtilis. In addition we isolated the protective molecule, exopolysaccharide (EPS) and shown EPS alone is sufficient for protection of disease. Food allergy and the anaphylactic response following allergen exposure are mediated by mast cell degranulation. We have evidence that EPS can suppress mast cell-dependent degranulation and anaphylaxis. Therefore, we hypothesize that EPS protects against anaphylaxis through the suppression of mast cell activation. Identifying the mechanism by which EPS prevents anaphylaxis will provide the first safe and effective therapeutic use of a probiotic for the treatment of food allergy.

Advance in studies on food allergy mechanism based on gut barrier

Food allergies, as a type of adverse immune-mediated reactions to ingested food proteins, have become a serious public health issue that harms children and adults health, with increasing incidence year by year. However, without effective therapy for food allergies, doctors-have mostly advised to avoid allergens and provided symptomatic treatment. According to the findings of many studies, allergic diseases are correlated with intestinal barrier function injury, as evidenced by the significant increase in the intestinal permeability among patients with food allergies. In this paper, recent studies on correlations between food allergies and intestinal barrier functions, intestinal barrier function injury mechanisms of allergic foods and food allergy intervention strategies based on intestinal barrier functions were summarized to provide reference for laboratory researches and clinical treatment of food allergic diseases.

Combined Probiotic and Peanut Oral Immunotherapy for the Treatment of Peanut Allergy: A Randomised Trial

Co-administration of a bacterial adjuvant with oral immunotherapy (OIT) has been suggested as a potential treatment for food allergy but such combined therapy has not previously been evaluated by randomized controlled trial.

Diagnosis, Management, and Investigational Therapies for Food Allergies

Food allergies have increased in prevalence over the past 20 years, now becoming an important public health concern. Although there are no therapies currently available for routine clinical care, recent reports have indicated that immunotherapies targeting the mucosal immune system may be effective. Oral immunotherapy is conducted by administering small, increasing amounts of food allergen; it has shown promise for desensitizing individuals with peanut, egg, or milk allergies. Sublingual immunotherapy also desensitizes allergic patients to foods-2 major studies have examined the effects of sublingual immunotherapy in subjects with peanut allergies. We review the complex nature of IgE-mediated food allergies and the therapies being evaluated in clinical trials. We focus on the diagnosis and management of food allergies and investigational therapies.

Epinephrine Use in Positive Oral Food Challenges Performed as a Screening Test for Food Allergy Therapy Trials

Previous studies report epinephrine use for positive oral food challenges (OFCs) to be 9-11% when generally performed to determine outgrowth of food allergies. Epinephrine use for positive OFCs performed as screening criteria for enrollment in therapeutic trials for food allergy has not been reported. The objective of this study was to assess the characteristics and treatment for positive OFCs performed for screening subjects for food therapeutic trials. Retrospective review of positive screening OFCs from 2 treatment trials, food allergy herbal formula-2 (n = 45) and milk oral immunotherapy (n = 29), conducted at the Icahn School of Medicine at Mount Sinai was performed. The most common initial symptom elicited was oral pruritus, reported for 81% (n = 60) of subjects. Overall, subjective gastrointestinal symptoms (oral pruritus, throat pruritus, nausea, abdominal pain) were most common (97.3% subjects), followed by cutaneous symptoms (48.7%). Of the 74 positive double-blind, placebo-controlled food challenge, 29 (39.2%) were treated with epinephrine; 2 of these subjects received 2 doses of epinephrine (6.9% of the reactions treated with epinephrine or 2.7% of all reactions). Biphasic reactions were infrequent, which occurred in 3 subjects (4%). Screening OFCs to confirm food allergies can be performed safely, but there was a higher rate of epinephrine use compared with OFCs used for assessing food allergy outgrowth. Therefore, personnel skilled and experienced in the recognition of early signs and symptoms of anaphylaxis who can promptly initiate treatment are required.

Diagnosis, Management, and Investigational Therapies for Food Allergies

Diagnosis, Management, and Investigational Therapies for Food Allergies

South African food allergy consensus document 2014

The prevalence of food allergy is increasing worldwide and is an important cause of anaphylaxis. There are no local South African food allergy guidelines. This document was devised by the Allergy Society of South Africa (ALLSA), the South African Gastroenterology Society (SAGES) and the Association for Dietetics in South Africa (ADSA). Subjects may have reactions to more than one food, and different types and severity of reactions to different foods may coexist in one individual. A detailed history directed at identifying the type and severity of possible reactions is essential for every food allergen under consideration. Skin-prick tests and specific immunoglobulin E (IgE) (ImmunoCAP) tests prove IgE sensitisation rather than clinical reactivity. The magnitude of sensitisation combined with the history may be sufficient to ascribe causality, but where this is not possible an incremental oral food challenge may be required to assess tolerance or clinical allergy. For milder non-IgE-mediated conditions a diagnostic elimination diet may be followed with food re-introduction at home to assess causality. The primary therapy for food allergy is strict avoidance of the offending food/s, taking into account nutritional status and provision of alternative sources of nutrients. Acute management of severe reactions requires prompt intramuscular administration of adrenaline 0.01 mg/kg and basic resuscitation. Adjunctive therapy includes antihistamines, bronchodilators and corticosteroids. Subjects with food allergy require risk assessment and those at increased risk for future severe reactions require the implementation of risk-reduction strategies, including education of the patient, families and all caregivers (including teachers), the provision of a written emergency action plan, a MedicAlert necklace or bracelet and injectable adrenaline (preferably via auto-injector) where necessary.

Elimination diets and dietary interventions for the management of food allergies Elimination diets and dietary interventions for the management of food allergies

The primary therapy for food allergy is strict avoidance of the offending food or foods. Dietary restriction should be tailored to meet the nutritional requirements of each patient.Patients should be educated on how to avoid allergens safely by understanding terminology for common ingredients and how to read food labels. Information regarding safe, cost-effective and freely available substitutes for the avoided foods should be provided. Patients should be re-evaluated at regular intervals to see if they have developed tolerance. Mothers of infants with cow’s milk protein allergy (CMPA) who are breastfeeding should be supported and encouraged to continue breastfeeding. Partially hydrolysed infant formulas are not hypoallergenic (tolerated by 90% of subjects with proven CMPA) and are therefore not recommended for the treatment of CMPA, but may have a role in prevention of eczema or CMPA in high-risk individuals. Some extensively hydrolysed and amino-acid-based formulas are truly hypoallergenic. The recommended feed of choice for the dietary management of mild-to-moderate CMPA in infants not breastfed is an extensively hydrolysed cow’s milk formula. The recommended formula for the dietary management of non-breastfed infants and children with known severe CMPA is an amino-acid-based formula. Soya-based formulas may be useful in infants with immunoglobulin E (IgE)-mediated CMPA with proven tolerance to soya, and some cases of mild-to-moderate non-IgE-mediated CMPA, bearing in mind the increased risk of co-reactivity between CMPA and soya allergy in non-IgE-mediated conditions. Other mammalian milks and plant-based milks, including rice and oat milks, are not suitable as sole nutrition for cow’s milk protein allergic individuals.

Shikonin, a constituent of Lithospermum erythrorhizon exhibits anti-allergic effects by suppressing orphan nuclear receptor Nr4a family gene expression as a new prototype of calcineurin inhibitors in mast cells

Over the last few decades, food allergy (FA) has become a common disease in infants in advanced countries. However, anti-allergic medicines available in the market have no effect on FA, and consequently effective drug therapies for FA are not yet available. We have already demonstrated that mucosal mast cells play an essential role in the development of FA in a murine model. Thus, we screened many constituents from medicinal herbs for the ability to inhibit rat basophilic leukemia-2H3 mast-like cell degranulation, and found that shikonin, a naphthoquinone dye from Lithospermum erythrorhizon, exhibited the most potent inhibitory effect among them. Furthermore, shikonin extremely inhibited the IgE/antigen-induced and calcium ionophore-induced upregulation of tumor necrosis factor (TNF)-α mRNA expression in mucosal-type bone marrow-derived mast cells (mBMMCs). Global gene expression analysis confirmed by real-time PCR revealed that shikonin drastically inhibited the IgE/antigen-induced and calcium ionophore-induced upregulation of mRNA expression of the nuclear orphan receptor 4a family (Nr4a1, Nr4a2 and Nr4a3) in mBMMCs, and knockdown of Nr4a1 or Nr4a2 suppressed the IgE/antigen-induced upregulation of TNF-α mRNA expression. Computational docking simulation of a small molecule for a target protein is a useful technique to elucidate the molecular mechanisms underlying the effects of drugs. Therefore, the simulation revealed that the predicted binding sites of shikonin to immunophilins (cyclophilin A and FK506 binding protein (FKBP) 12) were almost the same as the binding sites of immunosuppressants (cyclosporin A and FK506) to immunophilins. Indeed, shikonin inhibited the calcineurin activity to a similar extent as cyclosporin A that markedly suppressed the IgE/antigen-enhanced mRNA expression of TNF-α and the Nr4a family in mBMMCs. These findings suggest that shikonin suppresses mucosal mast cell activation by reducing Nr4a family gene expression through the inhibition of calcineurin activity. Therefore, shikonin has therapeutic potential for the treatment of allergic diseases as a new calcineurin inhibitor.

Epigenetics and development of food allergy (FA) in early childhood.

This review aims to highlight the latest advance on epigenetics in the development of food allergy (FA) and to offer future perspectives. FA, a condition caused by an immunoglobulin (Ig) E-mediated hypersensitivity reaction to food, has emerged as a major clinical and public health problem worldwide in light of its increasing prevalence, potential fatality, and significant medical and economic impact. Current evidence supports that epigenetic mechanisms are involved in immune regulation and that the epigenome may represent a key "missing piece" of the etiological puzzle for FA. There are a growing number of population-based epigenetic studies on allergy-related phenotypes, mostly focused on DNA methylation. Previous studies mostly applied candidate-gene approaches and have demonstrated that epigenetic marks are associated with multiple allergic diseases and/or with early-life exposures relevant to allergy development (such as early-life smoking exposure, air pollution, farming environment, and dietary fat). Rapid technological advancements have made unbiased genome-wide DNA methylation studies highly feasible, although there are substantial challenge in study design, data analyses, and interpretation of findings. In conclusion, epigenetics represents both an important knowledge gap and a promising research area for FA. Due to the early onset of FA, epigenetic studies of FA in prospective birth cohorts have the potential to better understand gene-environment interactions and underlying biological mechanisms in FA during critical developmental windows (preconception, in utero, and early childhood) and may lead to new paradigms in the diagnosis, prevention, and management of FA and provide novel targets for future drug discovery and therapies for FA.

Food Allergens: State of the Art in Piedmont Region in the Period 2011-2012.

The US National Institutes of Allergy and Infectious Diseases defines food allergy as adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Undeclared allergens in food label represent a risk for consumers, as there is no therapy for food allergies. According to Directive 2003/89/EC, declaration of all ingredients and derived substances in the label is mandatory. In 2011-2012, in Piedmont region (North-western Italy) 285 food samples were analysed for β-lactoglobulin and 234 for egg proteins. The aim of this work was to analyse 2 years data in order to assess the presence of undeclared milk and egg allergenic proteins in food placed on the market checking the compliance of labeling of food allergens. Analyses were carried out with ELISA tests, both for the detection of the egg and milk proteins. β-lactoglobulin was found in 2.8% (8/286) of samples, while egg proteins in 4.7% (11/234).

Multiple-allergen oral immunotherapy improves quality of life in caregivers of food-allergic pediatric subjects.

BackgroundFood allergy (FA) negatively affects quality of life in caregivers of food-allergic children, imposing a psychosocial and economic burden. Oral immunotherapy (OIT) is a promising investigational therapy for FA. However, OIT can be a source of anxiety as it carries risk for allergic reactions. The effect of OIT with multiple food allergens (mOIT) on FA-specific health-related quality of life (HRQL) has never been studied in participants with multiple, severe food allergies. This study is the first to investigate the effects of mOIT on FA-related HRQL in caregivers of pediatric subjects.MethodsCaregiver HRQL was assessed using a validated Food Allergy Quality of Life – Parental Burden (FAQL-PB) Questionnaire (J Allergy Clin Immunol 114(5):1159-1163, 2004). Parents of participants in two single-center Phase I clinical trials receiving mOIT (n = 29) or rush mOIT with anti-IgE (omalizumab) pre-treatment (n = 11) completed the FAQL-PB prior to study intervention and at 2 follow-up time-points (6 months and 18 months). Parents of subjects not receiving OIT (control group, n = 10) completed the FAQL-PB for the same time-points.ResultsHRQL improved with clinical (change < -0.5) and statistical (p < 0.05) significance in the mOIT group (baseline mean 3.9, 95% CI 3.4-4.4; 6-month follow-up mean 2.5, 95% CI 2.0-3.0; 18-month follow-up mean 1.8, 95% CI 1.4-2.1) and rush mOIT group (baseline mean 3.9, 95% CI 3.1-4.7; 6-month follow-up mean 1.7, 95% CI 0.9-2.6; 18-month follow-up mean 1.3, 95% CI 0.3-2.4). HRQL scores did not significantly change in the control group (n = 10).ConclusionMulti-allergen OIT with or without omalizumab leads to improvement in caregiver HRQL, suggesting that mOIT can help relieve the psychosocial and economic burden FA imposes on caregivers of food-allergic children.

Emerging therapies for food allergy.

Food allergy is a common condition for which there are currently no approved treatments except avoidance of the allergenic food and treatment of accidental reactions. There are several potential treatments that are under active investigation in animal and human studies, but it is not yet clear what the best approach may be. Here, we review approaches that are currently in clinical trials, including oral, sublingual, and epicutaneous immunotherapy, immunotherapy combined with anti-IgE, and Chinese herbal medicine as well as approaches that are in preclinical or early clinical investigation, including modified protein immunotherapy, adjuvants, DNA vaccines, and helminth administration. We discuss the importance of fully exploring the risks and benefits of any treatment before it is taken to general clinical practice and the need for clarity about the goals of treatment.

The Potential of Anti-IgE in Food Allergy Therapy.

Food allergy is an inappropriate immune response to certain food components. With its increasing prevalence over the past two decades, and potentially fatal consequences, food allergy has become a formidable public health issue. There is currently no effective therapy to treat food allergy. Patients are compelled to resort to strict avoidance of allergenic foods, and they must have quick access to emergency care in the event of accidental exposure. Clearly, there is an urgent need for treatment options. Allergen-specific and allergen-nonspecific therapeutic measures are being actively explored through ongoing research. The data thus far have identified the promise of oral immunotherapy (OIT) among allergen-specific and anti-IgE administration among allergen-nonspecific treatment modes. Indeed, results from three recent trials employing anti-IgE as an adjunctive therapy with OIT have indicated an outstanding potential to safely and rapidly desensitize patients with severe food allergies. The existing data set, however, is severely limited and is derived from diverse study designs that, in turn, have individual shortcomings. Readouts from current and proposed multicenter clinical trials following a well-designed uniform treatment protocol will be highly valuable for carrying out comparative analysis and to draw concrete inferences that will pave the way for approved food allergy therapy.

Future Therapies for IgE-Mediated Food Allergy.

Food allergy is prevalent, affecting approximately 4-8% of children. There is no currently approved treatment for food allergy, and while strict allergen avoidance is recommended it is difficult to achieve and therefore accidental exposures and reactions are common. There is an urgent need for the development of therapeutic approaches that will improve the health and quality of life of children with food allergy. The majority of current clinical research focus is on specific food allergen immunotherapy through oral, sublingual, or epicutaneous routes. Pre-clinical research has focused on making improvements to the safety and efficacy of allergen immunotherapy through modifications of allergen structure and addition of immuno-modulatory factors. The number of novel therapeutics for food allergy reaching the level of clinical trials remains disappointingly low, and there is a need for an expansion of pre-clinical research to provide safe, practical and novel approaches to the treatment of food allergy.

The Changing Geoepidemiology of Food Allergies

The science of food allergy has been rapidly evolving before our eyes in the past half century. Like other allergic disorders, the prevalence of food allergies has dramatically increased, and coupled with the increased public awareness of anaphylaxis due to food allergy, this has driven an explosion in basic and clinical research in this extremely broad subject. Treatment of food allergies has evolved and practices such as food challenges have become an integral part of an allergy practice. The impact of the increase of food allergy has driven package labeling laws, legislation on emergency treatment availability in schools and other public places, and school policy. But to this day, our knowledge of the pathogenesis of food allergy is still incomplete. There are the most obvious IgE-mediated immediate hypersensitivity reactions, but then multiple previously unidentified conditions such as eosinophilic esophagitis, food protein-induced enterocolitis syndrome, milk protein allergy, food-induced atopic dermatitis, oral allergy syndrome, and others have complicated the diagnosis and management of many of our patients who are unable to tolerate certain foods. Many of these conditions are not IgE-mediated, but may be T cell-driven diseases. The role of T regulatory cells and immune tolerance and the newly discovered immunological role of vitamin D have shed light on the variable clinical presentation of food allergy and the development of new methods of immunotherapy in an example of bench-to-bedside research. Component-resolved diagnostic techniques have already begun to allow us to more precisely define the epitopes that are targeted in food allergic patients. The development of biological modulators, research on genomics and proteomics, and epigenetic techniques all offer promising avenues for new modes of therapy of food allergy in the twenty-first century.

Food allergy diagnosis and therapy: where are we now?

Food allergy is a growing worldwide epidemic that adversely effects up to 10% of the population. Causes and risk factors remain unclear and diagnostic methods are imprecise. There is currently no accepted treatment for food allergy. Therefore, there is an imminent need for greater understanding of food allergies, revised diagnostics and development of safe, effective therapies. Oral immunotherapy provides a particularly promising avenue, but is still highly experimental and not ready for clinical use.