Future therapies for food allergy

Food allergy affects 3.9% of US children and is increasing in prevalence. The current standard of care involves avoidance of the triggering food and treatment for accidental ingestions. While there is no current curative treatment, there are a number of therapeutic strategies under investigation. Allergen specific therapies include oral and sublingual immunotherapy with native food protein as well as recombinant food proteins. Allergen non-specific therapies include a Chinese herbal formula (FAHF-2) and the use of anti-IgE monoclonal antibody therapy. Although none of these treatments are ready for clinical use, these therapeutic strategies present promising options for the future of food allergy

Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments. OBJECTIVE: We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. METHODS: We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium. RESULTS: We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD. CONCLUSION: Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets

Síndromes muy poco frecuentes

Dismorfología, Citogenética y Clínica: Resultados de estudios sobre los datos del ECEMCIn an attempt to facilitate the knowledge of the malformation syndromes that have very few frequencies to pediatricians and first health care physicians, particularly to those of rural areas, we have selected six new syndromes. As in previous years, the syndromes are selected from the ECEMC database registry. In this Boletín we include the following syndromes: Townes-Bröcks, MMT, Smith-Lemli-Opitz, Coffin-Siris, Espleno-gonadal fusion, and Silver-Russell syndromes. For each syndrome, we described the most important clinical characteristics, and the present knowledge of their causal factors.N

Cashew nut allergy: clinical relevance and allergen characterisation

Cashew plant (Anacardium occidentale L.) is the most relevant species of the Anacardium genus. It presents high economic value since it is widely used in human nutrition and in several industrial applications. Cashew nut is a well-appreciated food (belongs to the tree nut group), being widely consumed as snacks and in processed foods by the majority of world's population. However, cashew nut is also classified as a potent allergenic food known to be responsible for triggering severe and systemic immune reactions (e.g. anaphylaxis) in sensitised/allergic individuals that often demand epinephrine treatment and hospitalisation. So far, three groups of allergenic proteins have been identified and characterised in cashew nut: Ana o 1 and Ana o 2 (cupin superfamily) and Ana o 3 (prolamin superfamily), which are all classified as major allergens. The prevalence of cashew nut allergy seems to be rising in industrialised countries with the increasing consumption of this nut. There is still no cure for cashew nut allergy, as well as for other food allergies; thus, the allergic patients are advised to eliminate it from their diets. Accordingly, when carefully choosing processed foods that are commercially available, the allergic consumers have to rely on proper food labelling. In this sense, the control of labelling compliance is much needed, which has prompted the development of proficient analytical methods for allergen analysis. In the recent years, significant research advances in cashew nut allergy have been accomplished, which are highlighted and discussed in this review.This work was supported by FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT2020 with grant no. UID/QUI/50006/2013–POCI/01/ 0145/FEDER/007265. Joana Costa is grateful to FCT post-doctoral grant (SFRH/BPD/102404/2014) financed by POPH-QREN (subsidised by FSE and MCTES).info:eu-repo/semantics/publishedVersio

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Allergist-Reported Trends in the Practice of Food Allergen Oral Immunotherapy

Food allergen oral immunotherapy (OIT) is an experimental, immune-modifying therapy that may induce clinical desensitization in some patients. OIT is still in early phase clinical research, but some provider may offer OIT as a clinical service. To understand the current practices of allergists performing OIT an on-line survey was emailed to members of the American Academy of Allergy Asthma and Immunology. Among 442 respondents, 61 (13.8%) reported participating in OIT, including 28 in non-academic settings. Informed consent for OIT was obtained by 91.3%, IRB approval by 47.7% and Investigational New Drug (IND) approval by 38.1%. Compared to non-academic participants, more academic participants used peanut OIT, obtained IRB and IND (p <0.0001 respectively), and challenged patients prior to entry (p=0.008). More non-academic providers billed the patient or insurance for reimbursement (p<0.0001). Low reported regard for the importance for FDA approval or a standardized product (increased odds), and high regard for better safety data (decreased odds) were associated with considering to offer OIT as a service. Significant differences exist in OIT occurring in academic vs. non-academic settings. Further assessment is needed regarding the different motivations and practice styles among providers offering OIT, and those considering doing so

Pediatric oral food challenges in the outpatient setting: A single-center experience

Background: Oral food challenge (OFC) is the criterion standard for diagnosing food allergy (FA). It is important to have parameters to aid in selecting ideal OFC candidates. Objective: We sought to characterize outcomes and predictors of OFCs for common food allergens. Methods: We completed a retrospective chart review of all OFCs for IgE-mediated FA performed at Duke University pediatric allergy clinics from June 2017 through May 2022. Patients were deemed eligible for milk, egg, and nut OFC if testing revealed a specific IgE level not exceeding 2 kU/L and a skin prick test (SPT) resulting in a wheal size not exceeding 5 mm. Different parameters were followed for selecting candidates for baked challenge. Results: A total of 663 OFCs were conducted on 510 patients (59% male). The most common foods challenged were peanut (26%), plain egg (23%), baked egg (8%), and milk (8%), with pass rates of 84%, 88%, 62%, and 84%, respectively. Of the patients who failed OFC, 84% had objective symptoms, 23% had multisystemic reactions, and 15% required epinephrine. Although the presence of a personal or family history of atopy or prior failed OFC was not associated with outcomes, a history of anaphylaxis (regardless of the trigger) was associated with increased risk of failure. Conclusion: Although there are no established consensus guidelines, our study provides a benchmark illustrating that cutoffs of a specific IgE level not exceeding 2 kU/L and SPT finding not exceeding 5 mm result in a failure rate of approximately 13% for nonbaked milk, nonbaked egg, and nuts. The high rate of failed baked egg OFCs is likely related to selection bias, but our results illustrate the low negative predictive value of ovomucoid