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Two galactose-α-1,3-galactose carrying peptidases from pork kidney mediate anaphylactogenic responses in delayed meat allergy.

Abstract

BACKGROUND

Serum IgE antibodies directed at galactose-α-1,3-galactose (α-Gal) are associated with a novel form of delayed anaphylaxis occurring upon consumption of red meat or innards. Pork kidney is known as the most potent trigger of this syndrome, but the culprit allergens have not yet been identified. The aim of this study was the identification and characterization of pork kidney proteins mediating delayed anaphylactic reactions through specific IgE to α-Gal.

METHODS

A cohort of 59 patients with specific IgE to α-Gal was screened by immunoblot for IgE-reactive proteins in pork kidney. Proteins were identified by peptide mass fingerprinting. Isolated proteins were assayed in ELISA and ELISA inhibition, basophil activation and skin prick test.

RESULTS

Several IgE-binding proteins of high molecular weight (100- >200 kDa) were detected in pork kidney extracts by immunoblot using patient sera and an anti-α-Gal antibody. Two major IgE-binding proteins were identified as porcine angiotensin-I-converting enzyme (ACE I) and aminopeptidase N (AP-N). Reactivity of patient sera and anti-α-Gal antibody to both proteins was abolished by carbohydrate oxidation. The α-Gal IgE epitopes were resistant to heat denaturation. Pork kidney extract, isolated ACE I, and AP-N were able to activate patient basophils and elicit positive responses in skin prick tests.

CONCLUSION

Two cell-membrane proteins carrying α-Gal epitopes were identified in pork kidney. For the first time, isolated meat proteins were shown to induce basophil activation in patients with delayed anaphylaxis to red meat providing further confirmation for the clinical relevance of these α-Gal-carrying proteins.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg.

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    Department of Dermatology, Eberhard Karls University, Tuebingen, Germany.

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    Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg.

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    Immunology Allergology Unit, Centre Hospitalier, Luxembourg, Luxembourg.

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    Immunology Allergology Unit, Centre Hospitalier, Luxembourg, Luxembourg.

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    Department of Dermatology and Allergology, Technical University Munich, Munich, Germany.

    ,

    Immunology Allergology Unit, Centre Hospitalier, Luxembourg, Luxembourg.

    ,

    Department of Dermatology and Allergology, Technical University Munich, Munich, Germany.

    Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg. Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark.

    Source

    Allergy 71:5 2016 05 pg 711-9

    MeSH

    Allergens
    Anaphylaxis
    Animals
    Antibody Specificity
    Basophils
    Cattle
    Enzyme-Linked Immunosorbent Assay
    Epitopes
    Food Hypersensitivity
    Galactose
    Glycosylation
    Humans
    Hypersensitivity, Delayed
    Immunoglobulin E
    Peptide Hydrolases
    Red Meat
    Skin Tests
    Swine

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26728983

    Citation

    Hilger, C, et al. "Two Galactose-α-1,3-galactose Carrying Peptidases From Pork Kidney Mediate Anaphylactogenic Responses in Delayed Meat Allergy." Allergy, vol. 71, no. 5, 2016, pp. 711-9.
    Hilger C, Fischer J, Swiontek K, et al. Two galactose-α-1,3-galactose carrying peptidases from pork kidney mediate anaphylactogenic responses in delayed meat allergy. Allergy. 2016;71(5):711-9.
    Hilger, C., Fischer, J., Swiontek, K., Hentges, F., Lehners, C., Eberlein, B., ... Ollert, M. (2016). Two galactose-α-1,3-galactose carrying peptidases from pork kidney mediate anaphylactogenic responses in delayed meat allergy. Allergy, 71(5), pp. 711-9. doi:10.1111/all.12835.
    Hilger C, et al. Two Galactose-α-1,3-galactose Carrying Peptidases From Pork Kidney Mediate Anaphylactogenic Responses in Delayed Meat Allergy. Allergy. 2016;71(5):711-9. PubMed PMID: 26728983.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Two galactose-α-1,3-galactose carrying peptidases from pork kidney mediate anaphylactogenic responses in delayed meat allergy. AU - Hilger,C, AU - Fischer,J, AU - Swiontek,K, AU - Hentges,F, AU - Lehners,C, AU - Eberlein,B, AU - Morisset,M, AU - Biedermann,T, AU - Ollert,M, Y1 - 2016/01/27/ PY - 2016/01/02/accepted PY - 2016/1/6/entrez PY - 2016/1/6/pubmed PY - 2017/11/29/medline KW - Allergen KW - carbohydrate KW - galactose-α-1,3-galactose KW - pork kidney KW - red meat allergy SP - 711 EP - 9 JF - Allergy JO - Allergy VL - 71 IS - 5 N2 - BACKGROUND: Serum IgE antibodies directed at galactose-α-1,3-galactose (α-Gal) are associated with a novel form of delayed anaphylaxis occurring upon consumption of red meat or innards. Pork kidney is known as the most potent trigger of this syndrome, but the culprit allergens have not yet been identified. The aim of this study was the identification and characterization of pork kidney proteins mediating delayed anaphylactic reactions through specific IgE to α-Gal. METHODS: A cohort of 59 patients with specific IgE to α-Gal was screened by immunoblot for IgE-reactive proteins in pork kidney. Proteins were identified by peptide mass fingerprinting. Isolated proteins were assayed in ELISA and ELISA inhibition, basophil activation and skin prick test. RESULTS: Several IgE-binding proteins of high molecular weight (100- >200 kDa) were detected in pork kidney extracts by immunoblot using patient sera and an anti-α-Gal antibody. Two major IgE-binding proteins were identified as porcine angiotensin-I-converting enzyme (ACE I) and aminopeptidase N (AP-N). Reactivity of patient sera and anti-α-Gal antibody to both proteins was abolished by carbohydrate oxidation. The α-Gal IgE epitopes were resistant to heat denaturation. Pork kidney extract, isolated ACE I, and AP-N were able to activate patient basophils and elicit positive responses in skin prick tests. CONCLUSION: Two cell-membrane proteins carrying α-Gal epitopes were identified in pork kidney. For the first time, isolated meat proteins were shown to induce basophil activation in patients with delayed anaphylaxis to red meat providing further confirmation for the clinical relevance of these α-Gal-carrying proteins. SN - 1398-9995 UR - https://www.unboundmedicine.com/medline/citation/26728983/Two_galactose_α_13_galactose_carrying_peptidases_from_pork_kidney_mediate_anaphylactogenic_responses_in_delayed_meat_allergy_ L2 - https://doi.org/10.1111/all.12835 DB - PRIME DP - Unbound Medicine ER -