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

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

doi:10.1016/j.jaci.2021.07.018

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

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

Microbes, Infections and Microbiomes

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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.

Original language	English
Journal	Journal of Allergy and Clinical Immunology
Early online date	29 Jul 2021
DOIs	https://doi.org/10.1016/j.jaci.2021.07.018
Publication status	E-pub ahead of print - 29 Jul 2021

Bibliographical note

Funding Information:
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.).

Publisher Copyright:
© 2021 American Academy of Allergy, Asthma & Immunology

Keywords

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

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Cite this

Murangi, T., Prakash, P., Moreira, B. P., Basera, W., Botha, M., Cunningham, S., Facey-Thomas, H., Halajian, A., Joshi, L., Ramjith, J., Falcone, F. H., Horsnell, W., & Levin, M. E. (2021). Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome. Journal of Allergy and Clinical Immunology. Advance online publication. https://doi.org/10.1016/j.jaci.2021.07.018

@article{606feb730037490690877bb6b1855f7e,

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

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.",

keywords = "Alpha-gal, Amblyomma hebraeum, Ascaris lumbricoides, Rhipicephalus evertsi, anaphylaxis, food allergy, galactose-alpha-1,3-galactose, helminths, meat allergy, red meat allergy, ticks",

author = "Tatenda Murangi and Prema Prakash and Moreira, {Bernardo Pereira} and Wisdom Basera and Maresa Botha and Stephen Cunningham and Heidi Facey-Thomas and Ali Halajian and Lokesh Joshi and Jordache Ramjith and Falcone, {Franco H} and William Horsnell and Levin, {Michael E}",

note = "Funding Information: 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.). Publisher Copyright: {\textcopyright} 2021 American Academy of Allergy, Asthma & Immunology",

year = "2021",

month = jul,

day = "29",

doi = "10.1016/j.jaci.2021.07.018",

language = "English",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier",

}

Murangi, T, Prakash, P, Moreira, BP, Basera, W, Botha, M, Cunningham, S, Facey-Thomas, H, Halajian, A, Joshi, L, Ramjith, J, Falcone, FH, Horsnell, W & Levin, ME 2021, 'Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome', Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2021.07.018

TY - JOUR

T1 - Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome

AU - Murangi, Tatenda

AU - Prakash, Prema

AU - Moreira, Bernardo Pereira

AU - Basera, Wisdom

AU - Botha, Maresa

AU - Cunningham, Stephen

AU - Facey-Thomas, Heidi

AU - Halajian, Ali

AU - Joshi, Lokesh

AU - Ramjith, Jordache

AU - Falcone, Franco H

AU - Horsnell, William

AU - Levin, Michael E

N1 - Funding Information: 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.). Publisher Copyright: © 2021 American Academy of Allergy, Asthma & Immunology

PY - 2021/7/29

Y1 - 2021/7/29

N2 - 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.

AB - 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.

KW - Alpha-gal

KW - Amblyomma hebraeum

KW - Ascaris lumbricoides

KW - Rhipicephalus evertsi

KW - anaphylaxis

KW - food allergy

KW - galactose-alpha-1,3-galactose

KW - helminths

KW - meat allergy

KW - red meat allergy

KW - ticks

UR - http://www.scopus.com/inward/record.url?scp=85112509141&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2021.07.018

DO - 10.1016/j.jaci.2021.07.018

M3 - Article

C2 - 34333031

SN - 0091-6749

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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