Abstract
IgE antibodies to gal-α-1,3-gal-β-1,4-GlcNAc (α-gal) can mediate a novel form of delayed anaphylaxis to red meat. Although IgG antibodies to α-gal (anti-α-gal or anti-Gal) are widely expressed in humans, IgE anti-α-gal is not. We explored the relationship between the IgG and IgE responses to both α-gal and the related blood group B antigen. Contradicting previous reports, antibodies to α-gal were found to be significantly less abundant in individuals with blood group B or AB. Importantly, we established a connection between IgE and IgG responses to α-gal: elevated titers of IgG anti-α-gal were found in IgE-positive subjects. In particular, proportionally more IgG1 anti-α-gal was found in IgE-positive subjects against a background of IgG2 production specific for α-gal. Thus, two types of immune response to α-gal epitopes can be distinguished: a ‘typical’ IgG2 response, presumably in response to gut bacteria, and an ‘atypical’, Th2-like response leading to IgG1 and IgE in addition to IgG2. These results suggest that IgE to a carbohydrate antigen can be formed (probably as part of a glycoprotein or glycolipid) even against a background of bacterial immune stimulation with essentially the same antigen.
Highlights
IgE represents the class of antibodies that mediate hypersensitivity to a variety of allergens
Patients with pre-formed IgE antibodies to a-gal were found to suffer from anaphylactic reactions upon first exposure with cetuximab, a chimeric therapeutic antibody with murine variable domains that contains the a-gal epitope [5]
IgE Radioallergosorbent Test Serum IgE to a-gal and blood group B were measured by a radioallergosorbent test (RAST) using a-gal-HSA or blood group B-HSA coupled to Sepharose and detected by radiolabeled anti-IgE essentially as described before [23]. 1 mg of agal-HSA or blood group B-HSA was coupled to 100 mg of CNBr-activated Sepharose (Amersham Biosciences, Uppsala, Sweden)
Summary
IgE represents the class of antibodies that mediate hypersensitivity to a variety of allergens. Allergens are proteinaceous in nature and may induce formation of IgG antibodies as well as IgE antibodies. IgE may be directed to carbohydrate structures. -called cross-reactive carbohydrate determinants (CCD) can be targets for IgE responses [1], but the role of anti-CCD in triggering allergic symptoms is unclear [2]. It was recently found that some individuals can elicit an IgE response to the a-gal epitope [3;4]. Patients with pre-formed IgE antibodies to a-gal were found to suffer from anaphylactic reactions upon first exposure with cetuximab, a chimeric therapeutic antibody with murine variable domains that contains the a-gal epitope [5]. Cases of meat allergy have been linked to IgE anti-a-gal [6,7,8]
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