Project description:The prevalence of food allergy is rising and is estimated to approach 10%. Red meat allergy is the first known food allergy elicited by immunoglobulin E (IgE) antibodies recognizing a carbohydrate. Due to the loss of function of the alpha-1,3-galactosyltransferase (GGTA1) gene in humans, the disaccharide galactose-α-1,3-galactose (α-Gal) cannot be synthesized and therefore became immunogenic. IgE sensitization is elicited through the skin by repetitive tick bites transmitting α-Gal. The underlying mechanisms regarding innate and adaptive immune cell activation, including the B-cell isotype switch to IgE, are poorly understood, requiring further research and physiologically relevant animal models. Here, we describe a new animal model of red meat allergy using percutaneous α-Gal sensitization of gene-edited GGTA1-deficient pigs. Total and α-Gal-specific IgG, IgG1, IgG2, IgG4, and IgE levels were tracked. Further key factors associated with allergic skin inflammation, type 2 immunity, and allergy development were measured in PBMCs and skin samples. Significant increases in α-Gal-specific IgG1 and IgE levels indicated successful sensitization to the allergen α-Gal. Intracutaneous sensitizations with α-Gal recruited lymphocytes to the skin, including elevated numbers of T helper 2 (Th2) cells. Finally, α-Gal-sensitized pigs not only recognized α-Gal as non-self-antigen following α-Gal exposure through the skin but also developed anaphylaxis upon antigen challenge. Based on the similarities between the porcine and human skin, this new large animal model for α-Gal allergy should help to unveil the consecutive steps of cutaneous sensitization and aid the development of prophylactic and treatment interventions.

| S-EPMC10925645 | biostudies-literature

Glycolipid-mediated basophil activation in alpha-gal allergy.

Project description: Not available

| S-EPMC7670280 | biostudies-literature

Meat allergy associated with galactosyl-α-(1,3)-galactose (α-Gal)-Closing diagnostic gaps by anti-α-Gal IgE immune profiling.

Project description:BackgroundGlycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-α-(1,3)-galactose (α-Gal). It is known that α-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. α-Gal is part of the IgE-reactive monoclonal therapeutic antibody cetuximab (CTX) and is associated with delayed anaphylaxis to red meat. In this study, different α-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α-Gal.MethodsThree serum groups, α-Gal-associated meat allergy (MA) patients, idiopathic anaphylaxis (IA) patients with suspected MA, and non-meat-allergic healthy control individuals (HC), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for α-Gal-containing analytes CTX, bovine thyroglobulin (Bos d TG), and human serum albumin (HSA)-conjugated α-Gal.ResultsSingleplex allergy diagnostics using the α-Gal analytes CTX and Bos d TG confirms the history of MA patients in 91% and 88% of the cases, respectively. A novel dot blot-based assay system for the detection of IgE against α-Gal reveals individual IgE sensitization profiles for α-Gal-containing analytes. An α-Gal-associated IgE cross-reactivity profile (IgE against CTX, Bos d TG, and HSA-α-Gal) was identified, which is associated with MA.ConclusionsDetection of individual sensitization patterns with different α-Gal-containing analytes provides the basis for an individual allergy diagnosis for α-Gal-sensitized patients. Higher amounts of α-Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.

| S-EPMC7254904 | biostudies-literature

Identification of alpha-gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis.

Project description:IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs 3-6 hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha-gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked.

| S-EPMC7254893 | biostudies-literature

Establishing Standardized Documentation for Anaphylaxis Treatment in a Tertiary Care Pediatric Allergy Clinic.

Project description:IntroductionAnaphylaxis is a potentially life-threatening allergic reaction. Common allergy clinic procedures, including oral food challenges and subcutaneous immunotherapy, carry a risk of anaphylaxis, the treatment for which is epinephrine. Our goal was to develop a standardized process for the management and documentation of allergic reactions that occur in a tertiary care pediatric allergy clinic.MethodsThis was a single institution quality improvement pilot study. A multidisciplinary team from the allergy department designed, implemented, and studied the use of a standardized form for the documentation and treatment of allergic reactions within the clinic.ResultsA standardized form was developed based on evidence-based guidelines for the management of allergic reactions and included space for documentation. Both clinic providers and staff approved the form. One year after the introduction, we reached 100% adherence for the use of the form in visits during which a patient experienced a severe allergic reaction requiring epinephrine. Two patients required transfer to the emergency room; the quality improvement form was utilized in these cases to document treatment and assist with the hand-off to emergency room personnel before transfer.ConclusionsWe successfully implemented a standardized form for the treatment and documentation of anaphylaxis within our allergy clinic. The next steps focus on further integrating this form into the electronic medical record, determining compliance with evidence-based management of anaphylaxis, and formally assessing the use of the form as a handoff tool in the event of patient transfer.

| S-EPMC7190245 | biostudies-literature

Plaque Rupture-Induced Myocardial Infarction and Mechanical Circulatory Support in Alpha-Gal Allergy.

Project description:Alpha-gal (AG) allergy is an IgE-mediated allergic reaction to galactose-alpha-1,3-galactose found in mammalian meat. Heparin, being derived from porcine intestinal tissue, may have a degree of cross-reactivity with AG antigen and thus place patients at risk for allergic and even anaphylactic reactions. This is especially important in patients with myocardial infarction (MI) and mechanical circulatory support, such as a left ventricular assist device (LVAD), since anticoagulation is immediately required. Therefore, individualized assessment and preoperative planning is needed regarding the use of heparin vs. nonheparinoid products in such a population.

| S-EPMC7048905 | biostudies-literature

Tolerance of porcine pancreatic enzymes despite positive skin testing in alpha-gal allergy.

Project description: Not available

| S-EPMC7217730 | biostudies-literature

Regional and temporal awareness of alpha-gal allergy: An infodemiological analysis using Google Trends.

Project description: Not available

| S-EPMC7676348 | biostudies-literature