German Center for Lung Research

Connecting Diagnostics and Clinical Relevance of the α-Gal Syndrome-Individual Sensitization Patterns of Patients with Suspected α-Gal-Associated Allergy.

Sensitization to the carbohydrate antigen α-Gal is associated with allergic reactions against different types of food that contain α-Gal (e.g., mammalian meat). This form of allergy is termed α-Gal syndrome (AGS), and the diagnosis is challenging due to delayed symptom onset and cross-reactivity with multiple mammalian products. It is estimated that AGS is underdiagnosed, pointing to an unmet need for patient care. Sera from patients with suspected AGS based on clinical history were analyzed by ImmunoCAP and the IgE cross-reactivity immune profiling (ICRIP) system specifically developed by us. IgE from patient sera against different forms of α-Gal was analyzed using α-Gal-containing analytes and negative controls. Sera from 33 patients with suspected AGS were analyzed. Sera from 22 patients yielded a clearly positive signal (>0.35 kU/L) for IgE against α-Gal in ImmunoCAP. For 7 of the remaining 11 patients with negative or ambiguous (IgE level between 0.1 and 0.35 kU/L) results in ImmunoCAP, ICRIP analyses supported the suspected association of the allergy symptoms with IgE against α-Gal components. This component-resolved analysis helps the allergist to provide an individual diagnosis for each patient. The diagnosis of AGS is challenging. An interplay between clinical history and lab analysis via ImmunoCAP and the specifically developed ICRIP system helps patients and allergists in establishing the correct diagnosis, thereby preventing accidental exposure and recurrent AGS episodes.

Algorithms in allergy: An algorithm for alpha-Gal syndrome diagnosis and treatment, 2024 update.

Carbohydrate epitopes currently recognized as targets for IgE antibodies.

Until recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub-Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE-binding glycans recognized up to 2008 were considered to be "classical" cross-reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE-binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose-alpha-1,3-galactose (alpha-gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha-gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross-reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub-Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website (www.allergen.org). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed.

On the cause and consequences of IgE to galactose-α-1,3-galactose: A report from the National Institute of Allergy and Infectious Diseases Workshop on Understanding IgE-Mediated Mammalian Meat Allergy.

The mammalian meat allergy known as the "α-Gal syndrome" relates to IgE specific for galactose-α-1,3-galactose (α-Gal), an oligosaccharide that is present in cells and tissues of nonprimate mammals. The recognition of delayed reactions to food derived from mammals in patients with IgE to α-Gal and also the association with tick bites have been increasing worldwide. In 2018, the National Institute of Allergy and Infectious Diseases, Division of Allergy, Immunology and Transplantation, sponsored a workshop on this emerging tick-related disease. International experts from the fields of tick biology, allergy, immunology, infectious disease, and dermatology discussed the current state of our understanding of this emerging medical condition. The participants provided suggestions for specific research priorities and for the development of resources to advance our knowledge of the mechanisms, diagnosis, management, and prevention of this allergic disease. This publication is a summary of the workshop and the panel's recommendations are presented herein.

[Alpha-Gal-associated delayed red meat anaphylaxis as an occupational disease].

In a 30-year-old chef with recurrent delayed angioedema history as well as the experimental detection of IgE antibodies against galactose-alpha-(1,3)-galactose (alpha-Gal) pointed to alpha-Gal as the causative agent. The diagnosis, therefore, was delayed anaphylaxis due to alpha-Gal. Because of the potential relationship to his profession, we submitted a dermatologist's report BK 5101 to the liability and insurance association, whereupon his contract of employment was terminated without notice. As a consequence, we reported an occupational disease. This case demonstrates an underdiagnosed, potentially life-threatening allergy to the disaccharide alpha-Gal in red meat as an occupational disease.

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

Glycoproteins 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. Three 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. Singleplex 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. Detection 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.

Glycans and glycan-specific IgE in clinical and molecular allergology: Sensitization, diagnostics, and clinical symptoms.

Glycan-specific IgE antibodies cross-react with highly similar or even identical carbohydrate structures on a variety of different natural allergens, the so-called cross-reactive carbohydrate determinants (CCDs). In clinical practice CCDs often interfere with the specificity of in vitro allergy diagnostics, thus impairing allergy therapy decisions for individual patients. Strikingly, these IgE antibodies directed against CCDs often do not cause clinically relevant allergy symptoms. On the other hand, the IgE-binding glycan allergen galactose-α-(1,3)-galactose (α-Gal) is associated with IgE-mediated delayed anaphylaxis in meat allergy. The reason for this discrepancy is not known. The discovery of α-Gal stimulated new discussions and investigations regarding the relevance of anti-glycan IgE for allergic diseases. In this review the effect of glycans and glycan-specific IgE on sensitization to allergens and allergy diagnosis is described. Because parasite infections elicit a similar immunologic environment as allergic diseases, the association of glycan-specific antibodies against parasite glycoproteins with glycan structures on allergens is discussed.