Rurality and relative poverty drive acquisition of a stable and diverse gut microbiome in early childhood in a non-industrialized setting.

There are limited longitudinal data from non-industrialized settings on patterns and determinants of gut bacterial microbiota development in early childhood. We analysed epidemiological data and stool samples collected from 60 children followed from early infancy to 5 years of age in a rural tropical district in coastal Ecuador. Data were collected longitudinally on a wide variety of individual, maternal, and household exposures.

Historical Redlining Impacts Contemporary Environmental and Asthma-related Outcomes in Black Adults.

Environmental threats and poorly controlled asthma disproportionately burden Black people. Some have attributed this to socioeconomic or biologic factors; however, racism, specifically historical redlining, a U.S.

15LO1 dictates glutathione redox changes in asthmatic airway epithelium to worsen type 2 inflammation.

Altered redox biology challenges all cells, with compensatory responses often determining a cell's fate. When 15 lipoxygenase 1 (15LO1), a lipid-peroxidizing enzyme abundant in asthmatic human airway epithelial cells (HAECs), binds phosphatidylethanolamine-binding protein 1 (PEBP1), hydroperoxy-phospholipids, which drive ferroptotic cell death, are generated. Peroxidases, including glutathione peroxidase 4 (GPX4), metabolize hydroperoxy-phospholipids to hydroxy derivatives to prevent ferroptotic death, but consume reduced glutathione (GSH).

α-Gal specific-IgE prevalence and levels in Ecuador and Kenya: Relation to diet, parasites, and IgG.

Background: IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated.

Objective: We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya.

Glycolipid-mediated basophil activation in alpha-gal allergy.

Alpha-gal-containing glycolipids activate basophils sensitized with plasma from alpha-gal allergic subjects in an IgE-dependent manner suggesting a role for glycolipid in the effector phase of IgE-mediated food allergy.

Investigation into the α-Gal Syndrome: Characteristics of 261 Children and Adults Reporting Red Meat Allergy.

Background: Red meat allergy has historically been understood as a rare disease of atopic children, but the discovery of the "α-Gal syndrome," which relates to IgE to the oligosaccharide galactose-α-1,3-galactose (α-Gal), has challenged that notion.

Objective: To describe the clinical and immunologic characteristics of a large group of subjects with self-reported allergy to mammalian meat.

Methods: This was an observational study of 261 children and adults (range, 5-82 years) who presented for evaluation for allergic reactions to mammalian meat.

An integrated framework using high-dimensional mass cytometry and fluorescent flow cytometry identifies discrete B cell subsets in patients with red meat allergy.

Background: B cells play a critical role in the development and maintenance of food allergy by producing allergen-specific IgE. Despite the importance of B cells in IgE-mediated food allergy, the identity of sIgE-producing human B cells and how IgE is regulated are poorly understood.

Objective: To identify the immunophenotypes of circulating B cells associated with the production of galactose-alpha-1,3-galactose-specific IgE production in patients with red meat allergy.

IgE to the Mammalian Oligosaccharide Galactose-α-1,3-Galactose Is Associated With Increased Atheroma Volume and Plaques With Unstable Characteristics-Brief Report.

Objective: Emerging evidence suggests a link between coronary artery disease and type 2 immunity. We sought to test the hypothesis that IgE sensitization to the mammalian oligosaccharide galactose-α-1,3-galactose (α-Gal)-the target allergen of delayed anaphylaxis to red meat-is associated with coronary artery disease.

Approach And Results: Total IgE and specific IgE to α-Gal were assayed on sera from 118 subjects who presented for cardiac catheterization and underwent intravascular ultrasound.

Specific IgG antibodies to cow's milk proteins in pediatric patients with eosinophilic esophagitis.

Background: Allergen-specific IgG (sIgG) antibodies are often associated with tolerance, but sIgG antibodies to causally relevant foods have been reported recently in adults with eosinophilic esophagitis (EoE). Prevalence and levels of food sIgG are not well established in the general pediatric population.

Objective: We sought to investigate serum food sIgG with component diagnostics in children with EoE and children from an unselected birth cohort and to explore the effects of sex, age, and milk consumption on sIgG levels.

Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID).

Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults.

T1 signatures are present in the lower airways of children with severe asthma, regardless of allergic status.

Background: The pathogenesis of severe asthma in childhood remains poorly understood.

Objective: We sought to construct the immunologic landscape in the airways of children with severe asthma.

Methods: Comprehensive analysis of multiple cell types and mediators was performed by using flow cytometry and a multiplex assay with bronchoalveolar lavage (BAL) specimens (n = 68) from 52 highly characterized allergic and nonallergic children (0.

Galactose-α-1,3-Galactose: Atypical Food Allergen or Model IgE Hypersensitivity?

Purpose Of Review: Galactose-α-1,3-galactose (α-gal) is a carbohydrate allergen with several unique characteristics. In this article, we discuss some recent advances in our understanding of the 'alpha-gal syndrome,' highlight data supporting the role of ticks in pathogenesis, and speculate on immune mechanisms that lead to sensitization.

Recent Findings: First described as the target of IgE in individuals suffering immediate hypersensitivity reactions to the novel anti-EGF monoclonal antibody cetuximab, it is now clear that α-gal sensitization is associated with mammalian meat allergy as well as reactions to other mammalian products.

Anaphylaxis after zoster vaccine: Implicating alpha-gal allergy as a possible mechanism.

A patient with alpha-gal allergy presented with anaphylaxis after receiving zoster vaccine. Subsequent testing of selected vaccines revealed the presence of alpha-gal allergen in MMR and zoster vaccines, which have in common a higher content of gelatin and content of bovine calf serum.

Half-life of IgE in serum and skin: Consequences for anti-IgE therapy in patients with allergic disease.

We present results from clinical studies on plasma infusion done in the late 1970s in patients with hypogammaglobulinemia in which we documented the short half-life of both total and allergen-specific IgE in serum. The development of specific allergic sensitization in the skin of those patients followed by the gradual decrease in sensitization over 50 days was also documented. The data are included here along with a discussion of the existing literature about the half-life of IgE in both the circulation and skin.

Relevance of specific IgE antibody titer to the prevalence, severity, and persistence of asthma among 19-year-olds in northern Sweden.

Background: Although sensitization to indoor allergens is strongly associated with asthma, there are questions as to how this relates to asthma symptoms.

Objective: We sought to study the relevance of IgE antibodies to cat and dog allergens in an area in which (1) the climate discourages cockroach, fungal, and mite growth and (2) dander allergens are known to be present in schools and houses without animals.

Methods: IgE to 8 allergens was tested in 963 sera from a population-based study on 19-year-olds, and associations with asthma symptoms, diagnosis, and treatment were examined.

IgE in the diagnosis and treatment of allergic disease.

Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the "allergic" disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy.

IgE antibodies and response to cow's milk elimination diet in pediatric eosinophilic esophagitis.

Milk is a common cause of eosinophilic esophagitis. Allergy testing does not predict response to dietary therapy. In this study, patients with low or undetectable IgE antibodies to milk achieved histologic remission with milk elimination.

Allergens, sources, particles, and molecules: Why do we make IgE responses?

Allergens are foreign proteins or glycoproteins that are the target of IgE antibody responses in humans. The relationship between subsequent exposure and the allergic symptoms is often or usually obvious; however, there is increasing evidence that in asthma, atopic dermatitis and some forms of food allergy the induction of symptoms is delayed or chronic. The primary exposure to inhaled allergens is to the particles, which are capable of carrying allergens in the air.

Delayed Anaphylaxis Involving IgE to Galactose-alpha-1,3-galactose.

Hypersensitivity in the allergic setting refers to immune reactions, stimulated by soluble antigens that can be rapidly progressing and, in the case of anaphylaxis, are occasionally fatal. As the number of known exposures associated with anaphylaxis is limited, identification of novel causative agents is important in facilitating both education and other allergen-specific approaches that are crucial to long-term risk management. Within the last 10 years, several seemingly separate observations were recognized to be related, all of which resulted from the development of antibodies to a carbohydrate moiety on proteins where exposure differed from airborne allergens but which were nevertheless capable of producing anaphylactic and hypersensitivity reactions.

Risk factors for acute asthma in tropical America: a case-control study in the City of Esmeraldas, Ecuador.

Background: Despite the high asthma rates described in Latin America, asthma risk factors in poor urban settings are not well established. We investigated risk factors for acute asthma among Ecuadorian children.

Methods: A matched case-control study was carried out in a public hospital serving a coastal city.

Anaphylaxis to the carbohydrate side chain alpha-gal.

In 2007, the monoclonal antibody cetuximab caused severe hypersensitivity reactions during the first infusion in a region of the southeastern United States. Investigation of pretreatment sera established that they contained immunoglobulin (Ig) E against the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), which is present on the Fab of cetuximab. Alpha-gal is a blood group substance of nonprimate mammals.