The History of Carbohydrates in Type I Allergy

Abstract

Although first described decades ago, the relevance of carbohydrate specific antibodies as mediators of type I allergy had not been recognized until recently. Previously, allergen specific IgE antibodies binding to carbohydrate epitopes were considered to demonstrate a clinically irrelevant cross-reactivity. However, this changed following the discovery of type I allergies specifically mediated by oligosaccharide structures. Especially the emerging understanding of red meat allergy characterized by IgE directed to the oligosaccharide alpha-gal showed that carbohydrate-mediated reactions can result in life threatening systemic anaphylaxis which in contrast to former assumptions proves a high clinical relevance of some carbohydrate allergens. Within the scope of this review article, we illustrate the historical development of carbohydrate-allergen-research, reaching from only diagnostically relevant crossreactive-carbohydrate-determinants to clinically important antigens mediating type I allergy. Focusing on clinical and immunological features of the alpha-gal syndrome, we highlight the discovery of oligosaccharides as potentially highly immunogenic antigens and mediators of type I allergy, report what is known about the route of sensitization and the immunological mechanisms involved in sensitization and elicitation phase of allergic responses as well as currently available diagnostic and therapeutic tools. Finally, we briefly report on carbohydrates being involved in type I allergies different from alpha-gal.

Tuning IgE: IgE-Associating Molecules and Their Effects on IgE-Dependent Mast Cell Reactions

“…Upon clustering, the FcεRI β and γ chain ITAMs are phosphorylated An important variable of the naturally occurring IgEs is the heterogeneity of the polyclonal antibodies with different affinities against their target antigens. In addition, crossreactivity between different antigens has been reported in closely related antigens from different species (e.g., seed allergens [24]) and completely different molecules with similar modification epitopes (e.g., carbohydrate allergens [25]). Polyreactivity of monoclonal IgEs has also been reported [26].…”

Helminth infection induces non-functional sensitization to house dust mites

“…Indeed, sensitization to CCDs has been described during helminth infection [23,27,[30][31][32][33] and, with the exception of α-Gal [34], CCD-specific IgE are unable to trigger MCs or basophil degranulation in vivo. However, in vitro binding to anti-CCD IgE can result in cross-linking of FcεRI and activation of MCs, but it requires much higher concentrations [35].…”

Alpha-Gal-Syndrom

“…Die Oberflächen vieler Proteine und Lipide sind von Ketten aneinander gebundener Zuckermoleküle, sog. Polysacchariden, bedeckt und werden als Glykoproteine oder -lipide bezeichnet [ 1 ]. Der Rolle von Polysacchariden wurde in der Wissenschaft bislang relativ begrenzt Aufmerksamkeit geschenkt, dabei sind sie wichtig für Wachstum, Überleben, Strukturgebung, Schutz und Entwicklung eines Organismus.…”

“…Auch im Immunsystem bei der Unterscheidung zwischen „fremd“ und „eigen“ spielen sie eine wichtige Rolle. In der Allergologie sind auf Xylose und Fucose aufbauende Polysaccharide als Bindungsstellen für spezifisches Immunglobulin E (sIgE) seit Langem bekannt [ 1 ]. Diese bei Pflanzen und Insekten weit verbreiteten Epitope haben keine eigenständige klinische Relevanz.…”

“…Diese bei Pflanzen und Insekten weit verbreiteten Epitope haben keine eigenständige klinische Relevanz. Sie stellen in erster Linie eine zu falsch positiven Befunden führende Störgröße in der serologischen IgE(Immunglobulin E)-Diagnostik dar und werden in diesem Anwendungsbereich als kreuzreagierende Kohlenhydratdeterminanten (CCD) zusammengefasst [ 1 ].…”