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

Murangi, Tatenda; Prakash, Prema S.; Moreira, Bernardo Pereira; Basera, Wisdom; Botha, Maresa; Cunningham, Stephen; Facey‐Thomas, Heidi; Halajian, Ali; Joshi, Lokesh; Ramjith, Jordache; Falcone, Franco H.; Horsnell, William; Levin, Michael

doi:10.1016/j.jaci.2021.07.018

Cited by 18 publications

(16 citation statements)

References 38 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 3 , 15 , 45 , 49–51 The alpha-gal sensitization rates among rural children in lower- and middle-income countries may be due to increased exposures to alpha-gal-containing endo- and ectoparasites. 15 , 43 …”

Section: Epidemiology and Diagnosismentioning

confidence: 99%

“…The authors found the highest search volumes in Sweden, the United States, Canada, Australia, and South Africa. 42 In Southern Africa, the mechanism of sensitization is still not entirely clear, but may be secondary to tick bite, as alpha-gal glycoproteins have been identified in regionally endemic ticks, 43 or to other alpha-gal-bearing endoparasites. 43,44 The prevalence of alpha-gal sensitization varies depending on the region of the world, population studied, and the cutoff value for a positive alpha-gal IgE level.…”

Section: Epidemiology and Diagnosis Epidemiologymentioning

confidence: 99%

See 1 more Smart Citation

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

Macdougall¹,

Thomas²,

Iweala³

2022

ITT

View full text Add to dashboard Cite

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.

show abstract

Section: Epidemiology and Diagnosismentioning

confidence: 99%

Section: Epidemiology and Diagnosis Epidemiologymentioning

confidence: 99%

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

Macdougall¹,

Thomas²,

Iweala³

2022

ITT

View full text Add to dashboard Cite

show abstract

“…HEK293-6E cells grown in suspension were transfected with a polyethylenimine:DNA ratio of 3:1, using PEI MAX transfection grade linear 40 kDa polyethyleneimine from Polysciences (Warrington, PA, USA) as described before [ 15 ]. The transfected cells were grown in serum-free F17 medium at 37 °C under constant shaking for 5 days.…”

Section: Methodsmentioning

confidence: 99%

“…The advantages and disadvantages of RBL-based, humanised IgE reporters have been discussed in detail before [ 3 , 11 ]. Humanised IgE reporter systems have been used to elucidate an intriguing ‘outbreak’ of allergy to wheat hydrolysate containing cosmetic products in Japan [ 12 , 13 ], for the assessment of potential allergenicity of anti-helminthic vaccine candidates [ 14 ], to identify exposure to Ascaris lumbricoides as a potential cause underlying red meat allergy (Alpha-Gal sensitisation) [ 15 ] or to identify potential new allergens in black tiger shrimps [ 16 ], with another group suggesting that they may be superior to conventional diagnostic allergy tests in the case of shrimp allergy [ 17 ]. Here, we describe the generation and use of a faster, convenient new humanised fluorescent IgE reporter system, which does not require addition of any substrate and is, therefore, suitable for use in, e.g., high-throughput screening assays.…”

Section: Introductionmentioning

confidence: 99%

The Humanised NPY-mRFP RBL Reporter Cell Line Is a Fast and Inexpensive Tool for Detection of Allergen-Specific IgE in Human Sera

et al. 2022

Self Cite

View full text Add to dashboard Cite

Rat basophilic leukaemia (RBL) cells have been used for decades as a model of high-affinity Immunoglobulin E (IgE) receptor (FcεRI) signalling. Here, we describe the generation and use of huNPY-mRFP, a new humanised fluorescent IgE reporter cell line. Fusion of Neuropeptide Y (NPY) with monomeric red fluorescent protein (mRFP) results in targeting of fluorescence to the granules and its fast release into the supernatant upon IgE-dependent stimulation. Following overnight sensitisation with serum, optimal release of fluorescence upon dose-dependent stimulation with allergen-containing extracts could be measured after 45 min, without cell lysis or addition of any reagents. Five substitutions (D194A, K212A, K216A, K226A, and K230A) were introduced into the FcεRIα cDNA used for transfection, which resulted in the removal of known endoplasmic reticulum retention signals and high surface expression of human FcεRIα* in huNPY-mRFP cells (where * denotes the penta-substituted variant), comparable to the ~500,000 FcεRIα molecules per cell in the RS-ATL8 humanised luciferase reporter, which is a human FcεRIα/FcεRIγ double transfectant. The huNPY-mRFP reporter was used to demonstrate engagement of specific IgE in sera of Echinococcus granulosus-infected individuals by E. granulosus elongation factor EgEF-1β and, to a lesser extent, by EgEF-1δ, which had been previously described as IgE-immunoreactive EgEF-1β/δ.

show abstract

“…(3) from the parasitological point of view, as sensitization is linked to exposure to certain ticks and, as shown by us and others recently, to Ascaris lumbricoides (Wilson et al 2021) (Murangi et al 2021), it may represent the first example of food allergy induced by direct exposure (in contrast to ingestion) to parasites. IgE sensitization to α-Gal induced disease may also go beyond food allergy, as suggested by a recent work implying a link with cardiovascular disease (Wilson and Platts-Mills 2019).…”

Section: Humanized Ige Reporter Systems Are Extremely Sensitivementioning

confidence: 99%

Are humanized IgE reporter systems potential game changers in serological diagnosis of human parasitic infection?

et al. 2021

Self Cite

View full text Add to dashboard Cite

Immunoglobulin E (IgE) is thought to have evolved to protect mammalian hosts against parasitic infections or toxins and plays a central role in the pathogenesis, diagnosis, and therapy of IgE-mediated allergy. Despite the prominence of IgE responses in most parasitic infections, and in stark contrast to its use in the diagnosis of allergy, this isotype is almost completely unexploited for parasite diagnosis. Here, we discuss the perceived or real limitations of IgE-based diagnosis in parasitology and suggest that the recent creation of a new generation of very sensitive cellular IgE-based reporters may represent a powerful new diagnostic platform, but needs to be based on a very careful choice of diagnostic allergens.

show abstract

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

Cited by 18 publications

References 38 publications

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

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

The Humanised NPY-mRFP RBL Reporter Cell Line Is a Fast and Inexpensive Tool for Detection of Allergen-Specific IgE in Human Sera

Are humanized IgE reporter systems potential game changers in serological diagnosis of human parasitic infection?

Contact Info

Product

Resources

About