Galactose-α-1,3-Galactose–Specific IgE Is Associated with Anaphylaxis but Not Asthma

Commins, Scott P.; Kelly, Libby A.; Rönmark, Eva; James, Hayley R.; Pochan, S.L.; Peters, Edward J.; Lundbäck, Bo; Ng’ang’a, Lucy; Cooper, Philip J.; Hoskins, Janelle M.; Eapen, Saju S.; Matos, Luis A.; McBride, Dane C.; Heymann, Peter W.; Woodfolk, Judith A.; Perzanowski, Matthew S.; Platts-Mills, Thomas A.E.

doi:10.1164/rccm.201111-2017oc

Cited by 73 publications

(87 citation statements)

References 44 publications

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“…The 3 patients with IgE against α-Gal all ate red meat without having any acute or delayed symptoms. Commins et al [9] have reported that α-Gal titres among anaphylaxis-urticaria patients with red meat allergy make up at least 10% (or 30%) of total serum IgE. Upon investigating the fraction of α-Gal IgE to total IgE among our 3 patients, we found that it was less than 2%, supporting that the low titres we observed are not related to red meat allergy.…”

Section: Discussionsupporting

confidence: 80%

Galactose-α-1,3-Galactose Allergy Is Not a Hitherto Unrecognized Cause of Chronic Spontaneous Urticaria

Maurer

Church²,

Metz³

et al. 2015

Int Arch Allergy Immunol

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Background: Tick bite-induced galactose-α-1,3-galactose (α-Gal) IgE and subsequent ingestion of red meat may cause delayed severe allergic reactions including urticaria, gastrointestinal symptoms or anaphylaxis. We tested the hypothesis that increased levels of IgE to α-Gal due to tick bites and the subsequent ingestion of red meat or meat products may possibly be an un(der)recognized cause of chronic spontaneous urticaria (CSU). Methods: Levels of IgE to α-Gal and total IgE were measured (ImmunoCAP, Phadia AB/Thermo Fisher Scientific) in 83 patients (61 female and 22 male, median age 43 years, range 18-82) from the Department of Dermatology and Allergy, Charité - Universitätsmedizin, Berlin, Germany. All had been clinically diagnosed with moderate-to-severe CSU of a median duration of 2.9 years (range 0.1-50). Results: Eighty of the 83 patients (96%) had undetectable (<0.1 kU_A/l) serum levels of IgE against α-Gal. The levels in the remaining 3 were all low (0.25, 0.4 and 3.1 kU_A/l). In no patient, including those with measurable serum levels of IgE against α-Gal, was eating red meat associated with the development of symptoms of urticaria. Conclusion: Our results indicate that an allergic response to α-Gal is highly unlikely to be a hitherto unrecognized common cause of CSU.

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Section: Discussionsupporting

confidence: 80%

Galactose-α-1,3-Galactose Allergy Is Not a Hitherto Unrecognized Cause of Chronic Spontaneous Urticaria

Maurer

Church²,

Metz³

et al. 2015

Int Arch Allergy Immunol

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“…27 For example, cetuximab can generate an anaphylactic response due to its heterogeneous glycan forms, such as a-1,3 galactose and hydroxyacetylneuraminic acid (NGNA). 28 In our study of CTLA4-Ig glycosylation, we analyzed the biosimilar candidate using 3 different approaches: (1) intact protein level glycan analysis, (2) peptide level glycan analysis, and (3) cleaved glycan level analysis.…”

Section: Resultsmentioning

confidence: 99%

Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry

Zhu

Guo

Guo³

et al. 2014

mAbs

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These authors contributed equally to this work.Keywords: characterization, CTLA4-Ig fusion protein, glycan, glycosylation modification, intact protein, mass spectrometry, peptide mapping, similarity CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N-and O-glycosylation sites. Glycosylation plays a vital role in protein solubility, stability, serum half-life, activity, and immunogenicity. For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N-and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N-and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars.

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“…More recently, they have used antibodies against alpha-gal in human sera to stain the cryostat preparations of the tick which is thought to induce these responses in Stockholm [15 ▪▪ ]. The area of Sweden where we have screened sera from school children is almost 800 miles north of Stockholm and less than 1% of those sera tested positive for IgE to alpha-gal [30,31 ▪ ]. Interestingly, there are no ticks in that area.…”

Section: Late-onset and Delayed Reactions To Mammalian Food Products mentioning

confidence: 99%

Tick bites and red meat allergy

Commins¹,

Platts-Mills²

2013

Current Opinion in Allergy &Amp; Clinical Immunology

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121

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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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Galactose-α-1,3-Galactose–Specific IgE Is Associated with Anaphylaxis but Not Asthma

Abstract: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.

Cited by 73 publications

References 44 publications

Galactose-α-1,3-Galactose Allergy Is Not a Hitherto Unrecognized Cause of Chronic Spontaneous Urticaria

Galactose-α-1,3-Galactose Allergy Is Not a Hitherto Unrecognized Cause of Chronic Spontaneous Urticaria

Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry

Tick bites and red meat allergy

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