Determining the link between alpha-gal-containing antigens in North American ticks and red meat allergy

Crispell, Gary; Sp, Commins; Sa, Archer-Hartman; Choudhary, Sunil K.; Dharmarajan, Guha; Azadi, Parastoo; Karim, Shahid

doi:10.1101/505776

Cited by 3 publications

(4 citation statements)

References 40 publications

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“…The hIgE mAb to alpha-gal will enable better diagnostic tests for alpha-gal to be developed. Investigations of the immunopathogenesis of red meat allergy, including the presence of alpha-gal in the tick saliva and the role of alpha-gal in coronary artery disease, will also be facilitated (38)(39)(40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Unique allergen-specific human IgE monoclonal antibodies derived from patients with allergic disease

Smith,

Reid Black,

Bermingham

et al. 2023

Front. Allergy

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IntroductionAllergic reactions are mediated by human IgE antibodies that bind to and cross-link allergen molecules. The sites on allergens that are recognized by IgE antibodies have been difficult to investigate because of the paucity of IgE antibodies in a human serum. Here, we report the production of unique human IgE monoclonal antibodies to major inhaled allergens and food allergens that can be produced at scale in perpetuity.Materials and methodsThe IgE antibodies were derived from peripheral blood mononuclear cells of symptomatic allergic patients, mostly children aged 3–18 years, using hybridoma fusion technology. Total IgE and allergen-specific IgE was measured by ImmunoCAP. Their specificity was confirmed through ELISA and immunoblotting. Allergenic potency measurements were determined by ImmunoCAP inhibition. Biological activity was determined in vitro by comparing β-hexosaminidase release from a humanized rat basophilic cell line.ResultsHuman IgE monoclonal antibodies (n = 33) were derived from 17 allergic patients with symptoms of allergic rhinitis, asthma, atopic dermatitis, food allergy, eosinophilic esophagitis, or red meat allergy. The antibodies were specific for five inhaled allergens, nine food allergens, and alpha-gal and had high levels of IgE (53,450–1,702,500 kU/L) with ratios of specific IgE to total IgE ranging from <0.01 to 1.39. Sigmoidal allergen binding curves were obtained through ELISA, with low limits of detection (<1 kU/L). Allergen specificity was confirmed through immunoblotting. Pairs of IgE monoclonal antibodies to Ara h 6 were identified that cross-linked after allergen stimulation and induced release of significant levels of β-hexosaminidase (35%–80%) from a humanized rat basophilic cell line.ConclusionsHuman IgE monoclonal antibodies are unique antibody molecules with potential applications in allergy diagnosis, allergen standardization, and identification of allergenic epitopes for the development of allergy therapeutics. The IgE antibody probes will enable the unequivocal localization and validation of allergenic epitopes.

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Section: Discussionmentioning

confidence: 99%

Unique allergen-specific human IgE monoclonal antibodies derived from patients with allergic disease

Smith,

Reid Black,

Bermingham

et al. 2023

Front. Allergy

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“…Fischer et al ( 129 ), however, detected the presence of α-Gal epitopes in the midgut, hemolymph and salivary glands of I. ricinus females regardless of their feeding status. Meanwhile, three genes involved in the synthesis of α-Gal have been identified in I. scapularis genome ( 80 ) and the presence of α-Gal has also been confirmed in Amblyomma americanum ticks fed on human blood, which lacks α-Gal ( 130 ). All these findings support the view that α-Gal moieties present in tick tissues and saliva do not originate from a prior blood meal but are produced by the ticks themselves.…”

Section: Sensitization To α-Galmentioning

confidence: 99%

The α-Gal Syndrome and Potential Mechanisms

Román‐Carrasco

Hemmer²,

Cabezas-Cruz

et al. 2021

Front. Allergy

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The α-Gal syndrome is a complex allergic disease characterized by the development of specific IgE antibodies against the carbohydrate galactose-α-1,3-galactose (α-Gal), an oligosaccharide present in cells and tissues of non-primate mammals. Individuals with IgE antibodies to α-Gal suffer from a delayed form of anaphylaxis following red meat consumption. There are several features that make the α-Gal syndrome such a unique allergic disease and distinguish it from other food allergies: (1) symptoms causing IgE antibodies are directed against a carbohydrate moiety, (2) the unusual delay between the consumption of the food and the onset of the symptoms, and (3) the fact that primary sensitization to α-Gal occurs via tick bites. This review takes a closer look at the immune response against α-Gal, in healthy and in α-Gal allergic individuals. Furthermore, the similarities and differences between immune response against α-Gal and against the other important glycan moieties associated with allergies, namely cross-reactive carbohydrate determinants (CCDs), are discussed. Then different mechanisms are discussed that could contribute to the delayed onset of symptoms after consumption of mammalian meat. Moreover, our current knowledge on the role of tick bites in the sensitization process is summarized. The tick saliva has been shown to contain proteins carrying α-Gal, but also bioactive molecules, such as prostaglandin E2, which is capable of stimulating an increased expression of anti-inflammatory cytokines while promoting a decrease in the production of proinflammatory mediators. Together these components might promote Th2-related immunity and trigger a class switch to IgE antibodies directed against the oligosaccharide α-Gal. The review also points to open research questions that remain to be answered and proposes future research directions, which will help to get a better understanding and lead to a better management of the disease.

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“…Sensitization may be induced by ticks via the presence of mammalian blood in the tick midgut after a blood meal (12), the presence of endogenous tick alpha-gal antigens (including those found in non-fed larval ticks) (13) or alpha-gal producing tick-borne microbial pathogens (14). Recent studies have shown alphagal epitopes in the salivary glands of fed Amblyomma americanum and Ixodes scapularis (15), Ixodes. ricinus (9) and Haemaphysalis longicornis (16) and the mid-guts of ticks belonging to the Ixodes family, particularly I. ricinus (12) and I. scapularis (15).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have shown alphagal epitopes in the salivary glands of fed Amblyomma americanum and Ixodes scapularis (15), Ixodes. ricinus (9) and Haemaphysalis longicornis (16) and the mid-guts of ticks belonging to the Ixodes family, particularly I. ricinus (12) and I. scapularis (15). However, other organisms have not been rigorously examined for the presence of alpha-gal or their ability to induce IgE responses against alpha-gal.…”

Section: Introductionmentioning

confidence: 99%

Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome

Murangi

Prakash

Moreira

et al. 2022

Journal of Allergy and Clinical Immunology

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Determining the link between alpha-gal-containing antigens in North American ticks and red meat allergy

Cited by 3 publications

References 40 publications

Unique allergen-specific human IgE monoclonal antibodies derived from patients with allergic disease

Unique allergen-specific human IgE monoclonal antibodies derived from patients with allergic disease

The α-Gal Syndrome and Potential Mechanisms

Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome

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