The contribution made by skin‐infiltrating basophils to the development of alpha‐gal syndrome

Kageyama, Reiko; Fujiyama, Toshiharu; Satoh, Takahiro; Keneko, Yasuhito; Kitano, Seiya; Tokura, Y.; Hashizume, Hideo

doi:10.1111/all.13794

Cited by 14 publications

(14 citation statements)

References 8 publications

(7 reference statements)

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“…Additionally, T H 1 cells are involved in the pathogenesis of organ-specific autoimmune disorders, whereas T H 2 mediates allergen-specific responses (Romagnani, 1999). In humans, the AGS has been proposed to be associated with tick saliva-induced inhibition of T H 1-induced production of IL-1, basophil-mediated production of IL-4, decrease in T H 1/T H 2 ratio, and PGE 2 -induced antibody class switching, all resulting in the induction of T H 2-mediated IgE response against α-Gal (Cabezas-Cruz et al, 2019;Kageyama et al, 2019) (Figure 10B). As recently concluded by Kageyama et al (2019), repeated tick bites promote basophil recruitment and attract T H 2 cells to the skin, which results in a proper cytokine milieu to enhance IgE antibody levels against tick proteins and α-Gal to facilitate acquired immunity to ticks and the AGS.…”

Section: Discussionmentioning

confidence: 99%

“…Basophil levels increase and infiltrate lesions after tick infestations contributing to acquired immunity and secretion of the histamine-repellent factor in tick-resistant animals (Karasuyama et al, 2018b;Tabakawa et al, 2018). Basophils have been also shown to activate T H 2 IL-4-mediated responses (Karasuyama et al, 2018a), which may lead to acquired immunity to ticks and the high anti-α-Gal IgE antibody levels associated with the AGS (Kageyama et al, 2019). Additionally, basophils may attract T H 2 cells to the tick bite site to induce intrinsic T H 2 immunity-promoting adjuvant function of tick salivary components to enhance IgE response to α-Gal-containing tick proteins causing the AGS (Hilger et al, 2019;Kageyama et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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Allergic Reactions and Immunity in Response to Tick Salivary Biogenic Substances and Red Meat Consumption in the Zebrafish Model

Contreras

Pacheco

Alberdi

et al. 2020

Front. Cell. Infect. Microbiol.

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Ticks are arthropod ectoparasite vectors of pathogens and the cause of allergic reactions affecting human health worldwide. In humans, tick bites can induce high levels of immunoglobulin E antibodies against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) present in glycoproteins and glycolipids from tick saliva that mediate anaphylactic reactions known as the alpha-Gal syndrome (AGS) or red meat allergy. In this study, a new animal model was developed using zebrafish for the study of allergic reactions and the immune mechanisms in response to tick salivary biogenic substances and red meat consumption. The results showed allergic hemorrhagic anaphylactic-type reactions and abnormal behavior patterns likely in response to tick salivary toxic and anticoagulant biogenic compounds different from α-Gal. However, the results showed that only zebrafish previously exposed to tick saliva developed allergic reactions to red meat consumption with rapid desensitization and tolerance. These allergic reactions were associated with tissue-specific Toll-like receptor-mediated responses in types 1 and 2 T helper cells (T H 1 and T H 2) with a possible role for basophils in response to tick saliva. These results support previously proposed immune mechanisms triggering the AGS and provided evidence for new mechanisms also potentially involved in the AGS. These results support the use of the zebrafish animal model for the study of the AGS and other tick-borne allergies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Allergic Reactions and Immunity in Response to Tick Salivary Biogenic Substances and Red Meat Consumption in the Zebrafish Model

Contreras

Pacheco

Alberdi

et al. 2020

Front. Cell. Infect. Microbiol.

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“…Kageyama et al showed that basophils are recruited to tick bite site, in parallel with the increased anti-α-gal IgE levels. 123 Therefore, it can be postulated that basophils and their release of histamine might contribute at least in part to systemic anaphylaxis observed in the α-gal syndrome. It remains to be determined whether epidermal hyperplasia is observed in tick-infested skin lesions of α-gal-allergy patients.…”

Section: Role Of Basophil-derived Histamine In Tick Infestation and α-Gal Syndromementioning

confidence: 99%

“…Patients produce IgE against the carbohydrate, α‐gal, that is shared by tick saliva antigens, red meat and cetuximab. Kageyama et al showed that basophils are recruited to tick bite site, in parallel with the increased anti‐α‐gal IgE levels 123 . Therefore, it can be postulated that basophils and their release of histamine might contribute at least in part to systemic anaphylaxis observed in the α‐gal syndrome.…”

Section: Effector Functions Of Basophil‐derived Factorsmentioning

confidence: 99%

Basophils and their effector molecules in allergic disorders

Miyake

Shibata

Yoshikawa

et al. 2020

Allergy

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Basophils are the least common granulocytes which possess basophilic granules in their cytoplasm. Although they were first documented by Paul Ehrlich more than 140 years ago, their functional significance had long been an enigma, partly because of their rarity and the lack of analytical tools for basophils. In addition, basophils had been erroneously regarded as "blood-circulating mast cells," due to their similarities to tissue-resident mast cells, such as the expression of high-affinity IgE receptor (FcεRI) on their cell surface and the release of histamine upon their activation. Nevertheless, basophils and mast cells differ in a number of aspects. Basophils circulate in the peripheral blood under homeostatic conditions while mast cells typically reside in peripheral tissues and are hardly detected in the peripheral blood. Transcriptomic analyses revealed that basophils display distinct transcriptomic profiles from mast cells in both mice and humans. [1][2][3] Recent development of analytical tools for basophils has enabled us to identify nonredundant functions of basophils in multiple immune reactions, including allergic inflammation, and protective immunity against parasites. [4][5][6][7][8] In addition, the involvement of basophils is also demonstrated in several nonallergic disorders, such as lupus nephritis, 9-11 chronic obstructive pulmonary disease, 12 allograft rejection, 13,14 and carcinogenesis. 15,16 In this review, we summarize recent advances in our understanding of basophil biology, especially focusing on the roles of basophils in the context of allergic inflammation (Boxes 1 and 2). | ONTOG ENY OF BA SOPHIL SAlthough it is widely accepted that basophils differentiate from hematopoietic stem cells (HSCs), 17,18 the pathway of their differentiation

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“…Class switching to IgE as well as differentiation of type 2 helper T cells crucially requires the presence of the cytokine IL-4 and thus an initial cellular source of this Th2-associated cytokine, potentially basophils. Indeed, basophils have been shown to be recruited to the site of tick bites in an IL-3 and CD4 T cell dependent manner ( 142 ) and basophil numbers were enriched in the skin of alpha-gal-allergic patients at the site of tick bites ( 143 ). Taken together, allergic responses to carbohydrate allergens likely rely, similar to protein allergens, on antigen presentation by APCs, either via the classical MHCII pathway or, in the case of glycolipids, via CD1 molecules to T cells, and the subsequent T cell-dependent induction of B cell responses.…”

Section: Tolerance and Allergy To Carbohydrates – The Alpha-gal Storymentioning

confidence: 99%

The History of Carbohydrates in Type I Allergy

et al. 2020

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Although first described decades ago, the relevance of carbohydrate specific antibodies as mediators of type I allergy had not been recognized until recently. Previously, allergen specific IgE antibodies binding to carbohydrate epitopes were considered to demonstrate a clinically irrelevant cross-reactivity. However, this changed following the discovery of type I allergies specifically mediated by oligosaccharide structures. Especially the emerging understanding of red meat allergy characterized by IgE directed to the oligosaccharide alpha-gal showed that carbohydrate-mediated reactions can result in life threatening systemic anaphylaxis which in contrast to former assumptions proves a high clinical relevance of some carbohydrate allergens. Within the scope of this review article, we illustrate the historical development of carbohydrate-allergen-research, reaching from only diagnostically relevant crossreactive-carbohydrate-determinants to clinically important antigens mediating type I allergy. Focusing on clinical and immunological features of the alpha-gal syndrome, we highlight the discovery of oligosaccharides as potentially highly immunogenic antigens and mediators of type I allergy, report what is known about the route of sensitization and the immunological mechanisms involved in sensitization and elicitation phase of allergic responses as well as currently available diagnostic and therapeutic tools. Finally, we briefly report on carbohydrates being involved in type I allergies different from alpha-gal.

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The contribution made by skin‐infiltrating basophils to the development of alpha‐gal syndrome

Cited by 14 publications

References 8 publications

Allergic Reactions and Immunity in Response to Tick Salivary Biogenic Substances and Red Meat Consumption in the Zebrafish Model

Allergic Reactions and Immunity in Response to Tick Salivary Biogenic Substances and Red Meat Consumption in the Zebrafish Model

Basophils and their effector molecules in allergic disorders

The History of Carbohydrates in Type I Allergy

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