Meat allergy associated with galactosyl‐α‐(1,3)‐galactose (α‐Gal)—Closing diagnostic gaps by anti‐α‐Gal IgE immune profiling

Jappe, Uta; Minge, S; Kreft, Burkhard; Ludwig, Alika; Przybilla, Bernhard; Walker, Annett; Varga, Rita; Seidel, Philipp; Biedermann, Tilo; Anemüller, Waltraud; Kromminga, Arno; Ruëff, Franziska; Merk, Hans F.; Wagner, Nicola; Treudler, Regina; Worm, Margitta; Waldmann, Isabell; Saloga, Joachim; Becker, W.M.; Goldmann, Torsten; Platts-Mills, Thomas A.E.; Homann, Arne

doi:10.1111/all.13238

Cited by 44 publications

(35 citation statements)

References 26 publications

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“…2 ). The typical pattern for IgE against α-Gal (associated with meat allergy) could be identified for serum ADL86 as IgE binding to CTX, HSA-α-Gal and bovine TG 27 . No binding to glycan-processed CTX, to unconjugated HSA or human TG was detected, indicating the glycan-dependency.…”

Section: Resultsmentioning

confidence: 99%

Glycan and Peptide IgE Epitopes of the TNF-alpha Blockers Infliximab and Adalimumab - Precision Diagnostics by Cross-Reactivity Immune Profiling of Patient Sera

Homann

Röckendorf

Kromminga³

et al. 2017

Theranostics

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Biological drugs like therapeutic antibodies are widely used for the treatment of various diseases like inflammatory disorders and cancer. A drawback of these novel treatments is the substantial proportion of patients experiencing adverse reactions such as loss-of-drug effect or hypersensitivity reactions. These reactions are associated with pre-existing and/or developing anti-drug antibodies. Especially IgE development is a risk factor for life-threatening systemic anaphylaxis.Methods: In order to characterize the individual drug-specific serum IgE, an IgE cross-reactivity immune profiling (ICRIP) assay was developed. Individual IgG epitopes of anti-drug antibodies against adalimumab were identified by epitope mapping via peptide microarray.Results: ICRIP analyses of sera from patients treated with the therapeutic antibodies adalimumab (ADL) and infliximab (IFX) reveal individual, distinct IgE binding patterns. IgG epitopes were identified mostly located in the variable region of ADL.Conclusions: Using ICRIP and peptide microarrays for pharmacovigilance of the TNF-α blockers IFX and ADL, risk factors and biomarkers before and during therapy shall be identified. These diagnostic systems provide the basis for a safe and efficacious therapy decision for each patient in cases of adverse drug reactions mediated by different types of anti-drug antibodies.

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Section: Resultsmentioning

confidence: 99%

Glycan and Peptide IgE Epitopes of the TNF-alpha Blockers Infliximab and Adalimumab - Precision Diagnostics by Cross-Reactivity Immune Profiling of Patient Sera

Homann

Röckendorf

Kromminga³

et al. 2017

Theranostics

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“…This discrepancy raises the question whether aGal in the salivary N-glycome of the tick alone is the RMA sensitization factor. In addition, as mentioned above, the sIgE-based diagnostic assay found that the assay results included a substantial portion of false-positive results and difficulties in prediction of the allergic clinical symptoms [51,56,57].…”

Section: Agal In the Tick Sg As The Sensitizer Of Red Meat Allergymentioning

confidence: 91%

“…Red meat allergy (RMA) is an allergic reaction to aGal caused by a hypersensitive IgE response upon recognition of the glycan epitope. Although aGal has been well documented as an elicitor of RMA, the diagnostic test also suffers from sIgE-based assays for false-positive results [50][51][52][53][54][55][56][57]. The aGal allergy is also highly relevant to hyperreactions to xenoplantation [58] and to anti-cancer therapy using the monoclonal antibody cetuximab [59].…”

Section: Agal In the Tick Sg As The Sensitizer Of Red Meat Allergymentioning

confidence: 99%

Alpha-Gal and Cross-Reactive Carbohydrate Determinants in the N-Glycans of Salivary Glands in the Lone Star Tick, Amblyomma americanum

et al. 2020

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Ticks are important ectoparasites and vectors of numerous human and animal pathogens. Ticks secrete saliva that contains various bioactive materials to evade the host defense system, and often facilitates the pathogen transmission. In addition, the Lone star tick saliva is thought to be the sensitizer in red meat allergy that is characterized by an allergic reaction to glycan moieties carrying terminal galactose-alpha-1,3-galactose (aGal). To assess N-glycome of Amblyomma americanum, we examined the N-glycan structures in male and female salivary glands at three different feeding stages and in carcasses of partially fed lone star ticks. We also surveyed the genes involved in the N-glycosylation in the tick species. The aGal epitopes and cross-reactive carbohydrate determinants (CCD) increases over time after the onset of blood feeding in both male and female A. americanum. These CCDs include xylosylation of the core mannose, 1,3-mono and 1,3- and 1,6-difucosylations of the basal GlcNac and mono- or diantennary aGal. Combinations of both xylosylation and aGal and fucosylation and aGal were also found on the N-glycan structures. While the enzymes required for the early steps of the N-glycosylation pathway are quite conserved, the enzymes involved in the later stages of N-glycan maturation in the Golgi apparatus are highly diverged from those of insects. Most of all, we propose that the aGal serves as a molecular mimicry of bioactive proteins during tick feedings on mammalian hosts, while it contributes as a sensitizer of allergy in atypical host human.

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“…62 Cross-reactivity from the in vitro alpha-gal assay can occur with Bos d (beef) as a result of bovine thyroglobulin. 63 Although evidence exists for cross-reactivity with milk proteins, patients can generally tolerate low-fat milk and milkbased products.…”

Section: Ige To A-galmentioning

confidence: 99%

Idiopathic anaphylaxis yardstick

Carter

Akin

Castells

et al. 2020

Annals of Allergy, Asthma & Immunology

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Anaphylaxis is considered idiopathic when there is no known trigger. The signs and symptoms of idiopathic anaphylaxis (IA) are identical to those of anaphylaxis because of a known cause and can include cutaneous, circulatory, respiratory, gastrointestinal, and neurologic symptoms. Idiopathic anaphylaxis can be a frustrating disease for patients and health care providers. Episodes are unpredictable, and differential diagnosis is challenging. Current anaphylaxis guidelines have little specific guidance regarding differential diagnosis and long-term management of IA. Therefore, the objective of the Idiopathic Anaphylaxis Yardstick is to use published data and the authors' combined clinical experience to provide practical recommendations for the diagnosis and management of patients with IA.

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Meat allergy associated with galactosyl‐α‐(1,3)‐galactose (α‐Gal)—Closing diagnostic gaps by anti‐α‐Gal IgE immune profiling

Cited by 44 publications

References 26 publications

Glycan and Peptide IgE Epitopes of the TNF-alpha Blockers Infliximab and Adalimumab - Precision Diagnostics by Cross-Reactivity Immune Profiling of Patient Sera

Glycan and Peptide IgE Epitopes of the TNF-alpha Blockers Infliximab and Adalimumab - Precision Diagnostics by Cross-Reactivity Immune Profiling of Patient Sera

Alpha-Gal and Cross-Reactive Carbohydrate Determinants in the N-Glycans of Salivary Glands in the Lone Star Tick, Amblyomma americanum

Idiopathic anaphylaxis yardstick

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