Food-specific immunoglobulin A does not correlate with natural tolerance to peanut or egg allergens.

ImmunoglobulinA (IgA) is the predominant antibody isotype in the gut, where it regulates commensal flora and neutralizes toxins and pathogens. The function of food-specific IgA in the gut is unknown but is presumed to protect from food allergy. Specifically, it has been hypothesized that food-specific IgA binds ingested allergens and promotes tolerance by immune exclusion; however, the evidence to support this hypothesis is indirect and mixed.

Allergen-specific T cells and clinical features of food allergy: Lessons from CoFAR immunotherapy cohorts.

Background: Allergen-specific IL-4 and IL-13 CD4 cells (type 2 cells) are essential for helping B cells to class-switch to IgE and establishing an allergic milieu in the gastrointestinal tract. The role of T cells in established food allergy is less clear.

Objective: We examined the food allergen-specific T-cell response in participants of 2 food allergen immunotherapy trials to assess the relationship of the T-cell response to clinical phenotypes, including response to immunotherapy.

Bayesian hierarchical evaluation of dose-response for peanut allergy in clinical trial screening.

Risk-based labeling based on the minimal eliciting doses (EDs) in sensitized populations is a potential replacement for precautionary allergen labeling of food allergens. We estimated the dose-response distribution for peanut allergen using data from double-blind placebo-controlled food challenges (DBPCFCs) conducted in the US at multiple sites, testing a population believed to be similar to the general U.S.

Epicutaneous immunotherapy for treatment of peanut allergy: Follow-up from the Consortium for Food Allergy Research.

Background: Consortium for Food Allergy Research investigators previously reported 52-week outcomes from a randomized controlled trial of peanut epicutaneous immunotherapy, observing modest and statistically significant induction of desensitization, highest in children ages 4 to 11 years.

Objective: We sought to evaluate changes in efficacy, safety, and mechanistic parameters following extended open-label peanut epicutaneous immunotherapy.

Methods: Peanut-allergic participants (4-25 years) received 52 weeks of placebo (PLB), Viaskin Peanut 100 μg (VP100) or 250 μg (VP250), and then crossed over to VP250 for PLB (PLB-VP250) and VP100 (VP100-VP250) participants and continued treatment for VP250 participants (total = 130 weeks of active epicutaneous immunotherapy).

Early epitope-specific IgE antibodies are predictive of childhood peanut allergy.

Background: Peanut allergy is characterized by the development of IgE against peanut antigen.

Objective: We sought to evaluate the evolution of epitope-specific (es)IgE and esIgG in a prospective cohort of high-risk infants to determine whether antibody profiles can predict peanut allergy after age 4 years.

Methods: The end point was allergy status at age 4 years; samples from 293 children were collected at age 3 to 15 months and 2 to 3 and 4 years.

Induction of sustained unresponsiveness after egg oral immunotherapy compared to baked egg therapy in children with egg allergy.

Background: While desensitization and sustained unresponsiveness (SU) have been shown with egg oral immunotherapy (OIT), the benefits of baked egg (BE) therapy for egg allergy have not been well studied.

Objectives: This study sought to evaluate the safety and efficacy of BE ingestion compared with egg OIT in participants allergic to unbaked egg but tolerant to BE.

Methods: Children who are BE-tolerant but unbaked egg reactive ages 3 to 16 years were randomized to 2 years of treatment with either BE or egg OIT.

A 5-year summary of real-life dietary egg consumption after completion of a 4-year egg powder oral immunotherapy (eOIT) protocol.

The majority of children with sustained unresponsiveness after extended egg OIT are able to successfully introduce dietary egg. OIT outcome may be predictive of frequency, type (concentrated, baked), and quantity of egg ingested in the long term.

Clinical factors associated with peanut allergy in a high-risk infant cohort.

Background: Prognostication of peanut allergy (PNA) is relevant for early interventions. We aimed to determine baseline parameters associated with the development of PNA in 3- to 15-month-olds with likely egg and/or milk allergy, and/or moderate to severe atopic dermatitis (AD) and a positive egg/milk skin prick test (SPT), but no known PNA.

Methods: The primary endpoint was PNA [confirmed/convincing diagnosis or last classified as serologic PNA (<2 years, ≥5 kUA/L, otherwise ≥14 kUA/L, peanut IgE)] among 511 participants (median follow-up, 7.

Correction: A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration.

[This corrects the article DOI: 10.1371/journal.pone.

Multicenter, randomized, double-blind, placebo-controlled clinical trial of vital wheat gluten oral immunotherapy.

Background: Wheat is a common food allergen that can cause anaphylaxis.

Objective: We sought to determine the efficacy and safety of vital wheat gluten (VWG) oral immunotherapy (OIT).

Methods: After baseline double-blind, placebo-controlled food challenge (DBPCFC), 46 patients with wheat allergy (median age, 8.

A Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Utility of Tacrolimus (FK506) for the Prevention of Erectile Dysfunction Following Bilateral Nerve-Sparing Radical Prostatectomy.

Introduction: Radical prostatectomy (RP) is associated with erectile dysfunction, largely mediated through cavernous nerve injury. There are robust pre-clinical data supporting a potential role for neuromodulatory agents in this patient population. This study assessed tacrolimus in improving erectile function recovery rates after RP (ClinicalTrials.

Phenotypic Characterization of Eosinophilic Esophagitis in a Large Multicenter Patient Population from the Consortium for Food Allergy Research.

Background: Eosinophilic esophagitis (EoE) is increasingly common, but data on phenotypic aspects are still incomplete.

Objectives: To describe the clinical, endoscopic, and histopathologic features of a large number of children and adults with EoE across the United States.

Methods: This was a multisite single visit registry enrolling subjects aged 6 months to 65 years with EoE.

Egg-specific IgE and basophil activation but not egg-specific T-cell counts correlate with phenotypes of clinical egg allergy.

Background: Egg allergy is phenotypically heterogeneous. A subset of patients with egg allergy can tolerate egg in an extensively heated form. Inclusion of baked egg (BE) into the diet accelerates resolution of egg allergy.

Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults.

Background: Peanut allergy is common, life-threatening, and without therapeutic options. We evaluated peanut epicutaneous immunotherapy (EPIT) by using Viaskin Peanut for peanut allergy treatment.

Objective: We sought to evaluate the clinical, safety, and immunologic effects of EPIT for the treatment of peanut allergy.

Use of low-dose tacrolimus and associated hypomagnesemia in the prevention of erectile dysfunction following prostatectomy for prostate cancer.

Background: Hypomagnesemia with urinary magnesium wasting is a well described adverse event with calcineurin inhibitor therapy. Prostate cancer is the most prevalent cancer in men in the United States. Injury to the cavernous nerves during radical prostatectomy frequently results in erectile dysfunction.

Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy.

Background: We previously reported the results of a randomized placebo-controlled study of egg oral immunotherapy (eOIT) in which 27.5% of subjects achieved sustained unresponsiveness (SU) after 2 years. Here we report the results of treatment through 4 years and long-term follow-up.

A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy.

Background: Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy because benefits usually diminish when treatment is discontinued.

Objective: We sought to examine whether the addition of omalizumab to milk OIT reduces treatment-related reactions, improves outcomes, or both.

Methods: This was a double-blind, placebo-controlled trial with subjects randomized to omalizumab or placebo.

Sublingual immunotherapy for peanut allergy: Long-term follow-up of a randomized multicenter trial.

Background: We previously reported the initial results of the first multicenter, randomized, double-blind, placebo-controlled clinical trial of peanut sublingual immunotherapy (SLIT), observing a favorable safety profile associated with modest clinical and immunologic effects in the first year.

Objective: We sought to provide long-term (3-year) clinical and immunologic outcomes for our peanut SLIT trial. Key end points were (1) percentage of responders at 2 years (ie, could consume 5 g of peanut powder or a 10-fold increase from baseline), (2) percentage reaching desensitization at 3 years, (3) percentage attaining sustained unresponsiveness after 3 years, (4) immunologic end points, and (5) assessment of safety parameters.

Interleukin-2 receptor antagonist therapy leads to increased tacrolimus levels after kidney transplantation.

Background: Tacrolimus (TAC) is a known substrate for cytochrome P450 (CYP) enzyme. CYP enzyme activity can be modulated by activation of IL-2 receptors (IL-2R) expressed on hepatocytes and intestinal cells. IL-2R antagonists (IL-2RA) may promote preferential binding of circulating IL-2 to IL-2Rs on these cells by blocking IL-2Rs on activated T cells.

The natural history of milk allergy in an observational cohort.

Objective: There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes.

Methods: Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg.

Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial.

Background: There are presently no available therapeutic options for patients with peanut allergy.

Objective: We sought to investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT).

Methods: After a baseline oral food challenge (OFC) of up to 2 g of peanut powder (approximately 50% protein; median successfully consumed dose [SCD], 46 mg), 40 subjects, aged 12 to 37 years (median, 15 years), were randomized 1:1 across 5 sites to daily peanut or placebo SLIT.

Oral immunotherapy for treatment of egg allergy in children.

Background: For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy.

Methods: In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15).

Allergic reactions to foods in preschool-aged children in a prospective observational food allergy study.

Objective: To examine circumstances of allergic reactions to foods in a cohort of preschool-aged children.

Methods: We conducted a prospective, 5-site observational study of 512 infants aged 3 to 15 months with documented or likely allergy to milk or egg, and collected data prospectively examining allergic reactions.

Results: Over a median follow-up of 36 months (range: 0-48.

A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration.

Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH.

Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration.

Background: Age-related macular degeneration (AMD), a chronic neurodegenerative and neovascular retinal disease, is the leading cause of blindness in elderly people of western European origin. While structural and functional alterations in mitochondria (mt) and their metabolites have been implicated in the pathogenesis of chronic neurodegenerative and vascular diseases, the relationship of inherited variants in the mitochondrial genome and mt haplogroup subtypes with advanced AMD has not been reported in large prospective cohorts.

Methodology/prinicipal Findings: We examined the relationship of inherited mtDNA variants with advanced AMD in 1168 people using a three-stage design on samples from 12-year and 10-year prospective studies on the natural history of age-related eye disease.