Where’s the Beef? Understanding Allergic Responses to Red Meat in Alpha-Gal Syndrome

Carson, Audrey S.; Gardner, A. B.; Iweala, Onyinye I.

doi:10.4049/jimmunol.2100712

Cited by 19 publications

(43 citation statements)

References 109 publications

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“… Notes : a Common name and Geographic Range reported in Integrated Taxonomic Information System (ITIS, https://www.itis.gov/ ) 138 and/or reviewed in Carson AS, Gardner A, Iweala OI. 19 b Suspected link, but not definitive association of tick with the development of alpha-gal syndrome. …”

Section: Mechanisms Of Pathogenesismentioning

confidence: 99%

“…It has also been proposed that skin resident mast cells and circulating basophils are recruited to the site of the tick bite and stimulated to produce IL-4, a type 2, pro-allergic cytokine. 19 The presence of tick saliva-associated factors that act as adjuvants of immune responses, coupled with host alarmins, cytokines and other chemical defenses released by the breached skin epithelial barrier, may create a cytokine environment that pushes antibody-producing, alpha-gal specific B cells to make IgE against alpha-gal. 19 , 26 Transcriptional profiling of circulating peripheral blood mononuclear cells, 27 and animal models of AGS, 28 suggest that CD4 + Th2 cells, important in conventional allergies, may also play a role in allergic sensitization in AGS.…”

Section: Mechanisms Of Pathogenesismentioning

confidence: 99%

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The Meat of the Matter: Understanding and Managing Alpha-Gal Syndrome

Macdougall¹,

Thomas²,

Iweala³

2022

ITT

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Alpha-gal syndrome is an unconventional food allergy, characterized by IgE-mediated hypersensitivity responses to the glycan galactose-alpha-1,3-galactose (alpha-gal) and not to a food-protein. In this review, we discuss how alpha-gal syndrome reframes our current conception of the mechanisms of pathogenesis of food allergy. The development of alpha-gal IgE is associated with tick bites though the possibility of other parasites promoting sensitization to alpha-gal remains. We review the immune cell populations involved in the sensitization and effector phases of alpha-gal syndrome and describe the current understanding of why allergic responses to ingested alpha-gal can be delayed by several hours. We review the foundation of management in alpha-gal syndrome, namely avoidance, but also discuss the use of antihistamines, mast cell stabilizers, and the emerging role of complementary and alternative therapies, biological products, and oral immunotherapy in the management of this condition. Alpha-gal syndrome influences the safety and tolerability of medications and medical devices containing or derived from mammalian products and impacts quality of life well beyond food choices.

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Section: Mechanisms Of Pathogenesismentioning

confidence: 99%

Section: Mechanisms Of Pathogenesismentioning

confidence: 99%

The Meat of the Matter: Understanding and Managing Alpha-Gal Syndrome

Macdougall¹,

Thomas²,

Iweala³

2022

ITT

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“…[13][14][15][16][17] The mechanisms behind tick α-Gal induction of sensitization are still unknown, but besides the α-Gal moiety, tick sialome components may play an important role in the chained immune reaction activation (Figure 1). 18,19 Tick species such as Ixodes ricinus in Europe, Amblyomma americanum in North America, Haemaphysalis longicornis in Asia and Ixodes holocyclus in Australia are linked to AGS, 20 currently considered an emergent life-threatening allergy in tick endemic areas worldwide. [21][22][23] However, not all individuals bitten by ticks or those that carry elevated specific IgE (sIgE) against α-Gal develop AGS, in fact, the majority only produce sIgE against it.…”

Section: Introductionmentioning

confidence: 99%

Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)

Vaz-Rodrigues¹,

Mazuecos²,

Fuente³

2022

JAA

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The α-Gal syndrome (AGS) is a pathognomonic immunoglobulin E (IgE)-mediated delayed anaphylaxis in foods containing the oligosaccharide galactose-α-1,3-galactose (α-Gal) such as mammalian meat or dairy products. Clinical presentation of AGS can also comprise immediate hypersensitivity due to anticancer therapy, gelatin-containing vaccines or mammalian serum-based antivenom. The IgE initial sensitization is caused by hard-bodied tick bites and symptomatic individuals typically develop delayed pruritus, urticaria, angioedema, anaphylaxis, malaise or gut-related symptoms. Due to inapparent presentation, delayed reactions and a wide variety of patients´ clinical history, the AGS diagnosis and treatment remain challenging. This review covers not only current diagnostic methods used for AGS such as the skin prick test (SPT), the oral food challenge (OFC), anti-α-Gal IgE levels measurement and the basophil activation test (BAT), but also potentially relevant next-generation diagnostic tools like the mast cell activation test (MAT), the histamine-release (HR) assay, omics technologies and model-based reasoning (MBR). Moreover, it focuses on the therapeutical medical and non-medical methods available and current research methods that are being applied in order to elucidate the molecular, physiological and immune mechanisms underlying this allergic disorder. Lastly, future treatment and preventive tools are also discussed, being of utmost importance for the identification of tick salivary molecules, with or without α-Gal modifications, that trigger IgE sensitivity as they could be the key for further vaccine development. Bearing in mind climate change, the tick-host paradigm will shift towards an increasing number of AGS cases in new regions worldwide, which will pose new challenges for clinicians in the future.

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“…Immunoglobulin E (IgE) reactions against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) after tick bites may be associated with allergies to red meat, cetuximab, and gelatin [51][52][53][54]. The origin of these hypersensitivity reactions has not been precisely elucidated, and both adaptive and innate immune responses appear to be involved [55]. In any case, ticks can trigger the pathological specific immune responses by secretion of α-Gal in saliva (detected in the lone star tick, Amblyomma americanum, and Ixodes holocyclus) [56].…”

Section: Feeding and Salivary Secretionmentioning

confidence: 99%

The tick and I: Parasite‐host interactions between ticks and humans

Schön

2022

J Deutsche Derma Gesell

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Summary Ticks, particularly hard ticks (Ixodidae), which are among the most important vectors of dangerous infectious agents, feed on their hosts for extended periods of time. With this lifestyle, numerous adaptations have evolved in ticks and their hosts, the pharmacological importance of which is increasingly being recognized. Many bioactive substances in tick saliva are being considered as the basis of new drugs. For example, components of tick cement can be developed into tissue adhesives or wound closures. Analgesic and antipruritic salivary components inhibit histamine or bradykinin, while other tick‐derived molecules bind opioid or cannabinoid receptors. Tick saliva inhibits the extrinsic, intrinsic, or common pathway of blood coagulation with implications for the treatment of thromboembolic diseases. It contains vasodilating substances and affects wound healing. The broad spectrum of immunomodulatory and immunosuppressive effects of tick saliva, such as inhibition of chemokines or cellular immune responses, allows development of drugs against inflammation in autoimmune diseases and/or infections. Finally, modern vaccines against ticks can curb the spread of serious infections. The medical importance of the complex tick‐host interactions is increasingly being recognized and translated into first clinical applications. Using selected examples, an overview of the mutual adaptations of ticks and hosts is given here, focusing on their significance to medical advance.

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Where’s the Beef? Understanding Allergic Responses to Red Meat in Alpha-Gal Syndrome

Cited by 19 publications

References 109 publications

The Meat of the Matter: Understanding and Managing Alpha-Gal Syndrome

The Meat of the Matter: Understanding and Managing Alpha-Gal Syndrome

Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)

The tick and I: Parasite‐host interactions between ticks and humans

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