The Targets of IgE: Allergen-Associated and Tumor-Associated Molecular Patterns

Association between Allergies and Risk of Pancreatic Cancer

“…While there has been some speculation regarding possible biologic mechanisms, none are established. Allergic conditions have generally been associated with higher levels of allergen-specific IgE (54), and it has been suggested that IgE antibodies may recognize tumor antigens since the molecular epitope pattern determines whether an allergen elicits IgE synthesis/binding, and tumor cell antigens may exhibit similar epitope patterns, and therefore may also trigger IgE responses (55). IgE antibodies have been shown to be elevated in pancreatic cancer cases, compared to controls, and when isolated from pancreatic cancer patients have been shown to target pancreatic cancer antigens with subsequent cytotoxicity against pancreatic cancer cells (56).…”

Antacids and dietary supplements with an influence on the gastric pH increase the risk for food sensitization

“…Several additional proteins may cause symptoms due to cross-reactivity only, with the primary sensitizer being inhaled, because they are quickly degraded by pepsin at a low pH [20]. In addition to the stability of a protein, other factors may determine its sensitizing and allergen-triggering capacity, for instance, the likelihood of the formation of dimers or multimers [34,35]. Additionally, the genetic predisposition [36], the environmental influence like diesel-exhaust particles (reviewed in Bartra et al [36]), the hygienic status and the route of contact with the food -either via skin or via ingestion [37], the food matrix (reviewed in Nowak-Wegrzyn and Fiocchi [38]), the method of food processing (e.g.…”

IgE Immunotherapy Against Cancer

“…Type I hypersensitivity reactions are only induced by antigens that are able to engage multiple FcεRIs on effector cells (Kanner and Metzger 1983; Scholl et al 2005a; Segal et al 1977), resulting in cross-linking of FcεRI and the release of anaphylactic mediators. Since IgE antibodies are tightly bound to their FcεRI receptor in a bent form (Gould et al 2003), more then 2 antigen epitopes have to be displayed rather rigidly in a specific range of spatial conformation in order to cross-link IgE bound to FcεRI and induce its downstream effects (Holowka et al 2007; Jensen-Jarolim et al 2010). Molecules present in high density, such as certain overexpressed tumor antigens that are tightly packed on cell membranes or in lipid rafts, may cross-link FcεRI by forming tumor-associated molecular patterns, inducing a type I hypersensitivity reaction within the tumor microenvironment and resulting in tumor cytotoxicity (Jensen-Jarolim et al 2010).…”

“…Since IgE antibodies are tightly bound to their FcεRI receptor in a bent form (Gould et al 2003), more then 2 antigen epitopes have to be displayed rather rigidly in a specific range of spatial conformation in order to cross-link IgE bound to FcεRI and induce its downstream effects (Holowka et al 2007; Jensen-Jarolim et al 2010). Molecules present in high density, such as certain overexpressed tumor antigens that are tightly packed on cell membranes or in lipid rafts, may cross-link FcεRI by forming tumor-associated molecular patterns, inducing a type I hypersensitivity reaction within the tumor microenvironment and resulting in tumor cytotoxicity (Jensen-Jarolim et al 2010). Importantly, no systemic reactions have been observed in the various in vivo cancer models examined via a range of approaches by multiple independent groups, aimed to address IgE-mediated activity in cancer immunotherapy in the studies described above.…”