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Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome - 03/02/22

Doi : 10.1016/j.jaci.2021.07.018 
Tatenda Murangi, Bsc (Hons) a, Prema Prakash, PhD b, Bernardo Pereira Moreira, PhD b, Wisdom Basera, MPH c, d, Maresa Botha, MD e, Stephen Cunningham, PhD f, Heidi Facey-Thomas, DipNursCert e, Ali Halajian, PhD g, Lokesh Joshi, PhD f, Jordache Ramjith, MSc h, Franco H. Falcone, PhD b, , William Horsnell, PhD a, i, , Michael E. Levin, PhD e,
a Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, Division of immunology, University of Cape Town, Cape Town, South Africa 
b Institute of Parasitology, Biomedical Research Center Seltersberg, Justus Liebig University Giessen, Giessen, Germany 
c School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa 
d Burden of Disease Research Unit, South African Medical Research Council, Cape Town, South Africa 
e Division of Paediatric Allergy, Department of Paediatrics, University of Cape Town, Cape Town, South Africa 
f Glycoscience Group, Biomedical Sciences, National University of Ireland Galway, Galway, Ireland 
g Research Administration and Development, University of Limpopo, Sovenga, South Africa 
h Department for Health Evidence, Biostatistics Research Group, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands 
i Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom 

Corresponding author: Michael Levin, PhD, Room 516, ICH building, Red Cross Children’s Hospital, Klipfontein Road, Cape Town, South Africa.Room 516, ICH building, Red Cross Children’s HospitalKlipfontein RoadCape TownSouth Africa

Abstract

Background

IgE to galactose alpha-1,3 galactose (alpha-gal) causes alpha-gal syndrome (delayed anaphylaxis after ingestion of mammalian meat). Development of sensitization has been attributed to tick bites; however, the possible role of other parasites has not been well studied.

Objective

Our aims were to assess the presence, relative abundances, and site of localization of alpha-gal–containing proteins in common ectoparasites and endoparasites endemic in an area of high prevalence of alpha-gal syndrome, as well as to investigate the ability of ascaris antigens to elicit a reaction in a humanized rat basophil in vitro sensitization model.

Methods

Levels of total IgE, Ascaris-specific IgE, and alpha-gal IgE were measured in sera from patients with challenge-proven alpha-gal syndrome and from controls without allergy. The presence, concentration, and localization of alpha-gal in parasites were assessed by ELISA, Western blotting, and immunohistochemistry. The ability of Ascaris lumbricoides antigen to elicit IgE-dependent reactivity was demonstrated by using the RS-ATL8 basophil reporter system.

Results

Alpha-gal IgE level correlated with A lumbricoides–specific IgE level. Alpha-gal protein at 70 to 130 kDa was detected in A lumbricoides at concentrations higher than those found in Rhipicephalus evertsi and Amblyomma hebraeum ticks. Immunohistochemistry was used to localize alpha-gal in tick salivary acini and the helminth gut. Non–alpha-gal–containing A lumbricoides antigens activated RS-ATL8 basophils primed with serum from subjects with alpha-gal syndrome.

Conclusion

We demonstrated the presence, relative abundances, and site of localization of alpha-gal–containing proteins in parasites. The activation of RS-ATL8 IgE reporter cells primed with serum from subjects with alpha-gal syndrome on exposure to non–alpha-gal–containing A lumbricoides proteins indicates a possible role of exposure to A lumbricoides in alpha-gal sensitization and clinical reactivity.

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Key words : Alpha-gal, food allergy, galactose-alpha-1,3-galactose, helminths, meat allergy, red meat allergy, ticks, Ascaris lumbricoides, anaphylaxis, Rhipicephalus evertsi, Amblyomma hebraeum

Abbreviations used : Alpha-gal, Asc l, E/S, BTG, GSI-B4, HRP, PBS-T, scFv, Strep-HRP


Mappa


 Supported by the Birmingham-Nottingham Strategic Collaboration Fund (to W.G.C.H. and F.H.F.); the LOEWE Centre DRUID within the Hessian Excellence Initiative (P.P., B.P.M., and F.H.F.), and a National Research Foundation Innovation M&D Scholarship (to T.M.).
 Disclosure of potential conflicts of interest: The authors declare that they have no relevant conflicts of interest.


© 2021  American Academy of Allergy, Asthma & Immunology. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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