Close-up of the Immunogenic α1,3-Galactose Epitope as Defined by a Monoclonal Chimeric Immunoglobulin E and Human Serum Using Saturation Transfer Difference (STD) NMR

Plum, Melanie; Michel, Yvonne; Wallach, Katharina; Raiber, Tim; Blank, Simon; Bantleon, Frank; Diethers, Andrea; Greunke, Kerstin; Braren, Ingke; Hackl, Thomas; Meyer, Bernd; Spillner, Edzard

doi:10.1074/jbc.m111.291823

Cited by 28 publications

(22 citation statements)

References 60 publications

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“…It appears that binding to α-gal is largely determined by the terminal galactoses, as has been suggested by others [28]; [30]. Specificity to α-gal on the other hand may be also determined by the proximal sugar residues of α-gal and related sugar epitopes, B in particular.…”

Section: Discussionsupporting

confidence: 52%

IgE Production to α-Gal Is Accompanied by Elevated Levels of Specific IgG1 Antibodies and Low Amounts of IgE to Blood Group B

et al. 2013

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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.

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Section: Discussionsupporting

confidence: 52%

IgE Production to α-Gal Is Accompanied by Elevated Levels of Specific IgG1 Antibodies and Low Amounts of IgE to Blood Group B

et al. 2013

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“…Using nuclear magnetic resonance, it has been confirmed that the antibodies are primarily directed at the 2 terminal galactoses. 26 The ongoing IgG Ab response to α -gal, thought to be induced by continuous antigenic stimulation in the gut, is predominantly IgG2. 27 After tick bites, the IgG antibodies increase in parallel with IgE antibodies, but they are predominantly IgG1.…”

Section: Development Of Ige To α-Gal Responsementioning

confidence: 99%

Drug allergens and food—the cetuximab and galactose-α-1,3-galactose story

Berg

Platts-Mills

Commins

2014

Annals of Allergy, Asthma & Immunology

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Objective A novel form of food allergy has been described that initially became apparent from IgE reactivity with the drug cetuximab. Ongoing work regarding the etiology, distribution, clinical management, and cellular mechanisms of the IgE response to the oligosaccharide galactose-α-1,3-galactose (α-gal) is reviewed. Data Sources Brief review of the relevant literature in peer-reviewed journals. Study Selection Studies on the clinical and immunologic features, pathogenesis, epidemiology, laboratory evaluation, and management of IgE to α-gal are included in this review. Results Recent work has identified a novel IgE antibody response to the mammalian oligosaccharide epitope, α-gal, that has been associated with 2 distinct forms of anaphylaxis: (1) immediate-onset anaphylaxis during first exposure to intravenous cetuximab and (2) delayed-onset anaphylaxis 3 to 6 hours after ingestion of mammalian food products (eg, beef and pork). Study results have suggested that tick bites are a cause of IgE antibody responses to α-gal in the United States. Patients with IgE antibody to α-gal continue to emerge, and, increasingly, these cases involve children. Nevertheless, this IgE antibody response does not appear to pose a risk for asthma but may impair diagnostic testing in some situations. Conclusion The practicing physician should understand the symptoms, evaluation, and management when diagnosing delayed allergic reactions to mammalian meat from IgE to α-gal or when initiating treatment with cetuximab in patients who have developed an IgE antibody response to α-gal.

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“…Using NMR, it has been confirmed that the antibodies are primarily directed at the two terminal galactoses [20]. It is important to remember that all immuno-competent humans (as well as Old World monkeys and apes) have circulating IgG antibodies to alpha-gal [21].…”

Section: Ticks and Ige Antibody Responsesmentioning

confidence: 99%

Tick bites and red meat allergy

Commins¹,

Platts-Mills²

2013

Current Opinion in Allergy &Amp; Clinical Immunology

119

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Purpose of review A novel form of anaphylaxis has been described that is due to IgE antibody (Ab) directed against a mammalian oligosaccharide epitope, galactose-alpha-1, 3-galactose (alpha-gal). Ongoing work regarding the cause and distribution of this IgE response is reviewed. Recent findings Our recent work has identified a novel IgE Ab response that has been associated with two distinct forms of anaphylaxis: immediate-onset anaphylaxis during first exposure to intravenous cetuximab and delayed-onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g. beef and pork). Further studies strongly suggested that tick bites were a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the United States and internationally. Summary Large numbers of patients with IgE Ab to alpha-gal continue to be identified in the USA and globally. Clinicians should be aware of this IgE response as the reactions often appear to be idiopathic because of the significant delay between eating mammalian meat and the appearance of symptoms.

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Close-up of the Immunogenic α1,3-Galactose Epitope as Defined by a Monoclonal Chimeric Immunoglobulin E and Human Serum Using Saturation Transfer Difference (STD) NMR

Cited by 28 publications

References 60 publications

IgE Production to α-Gal Is Accompanied by Elevated Levels of Specific IgG1 Antibodies and Low Amounts of IgE to Blood Group B

IgE Production to α-Gal Is Accompanied by Elevated Levels of Specific IgG1 Antibodies and Low Amounts of IgE to Blood Group B

Drug allergens and food—the cetuximab and galactose-α-1,3-galactose story

Tick bites and red meat allergy

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