Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization
Background: Immunoglobulin-E(IgE)-mediated hypersensitivity to cow’s milk allergens is a frequent cause of severe and life-threatening anaphylactic reactions. Besides case histories and controlled food challenges, the detection of the IgE antibodies specific to cow’s milk allergens is important for...
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MDPI AG
2023-05-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/10/2401 |
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| author | Victoria Garib Daria Trifonova Raphaela Freidl Birgit Linhart Thomas Schlederer Nikolaos Douladiris Alexander Pampura Daria Dolotova Tatiana Lepeshkova Maia Gotua Evgeniy Varlamov Evgeny Beltyukov Veronika Naumova Styliani Taka Alina Kiyamova Stefani Katsamaki Alexander Karaulov Rudolf Valenta |
| author_facet | Victoria Garib Daria Trifonova Raphaela Freidl Birgit Linhart Thomas Schlederer Nikolaos Douladiris Alexander Pampura Daria Dolotova Tatiana Lepeshkova Maia Gotua Evgeniy Varlamov Evgeny Beltyukov Veronika Naumova Styliani Taka Alina Kiyamova Stefani Katsamaki Alexander Karaulov Rudolf Valenta |
| author_sort | Victoria Garib |
| collection | DOAJ |
| description | Background: Immunoglobulin-E(IgE)-mediated hypersensitivity to cow’s milk allergens is a frequent cause of severe and life-threatening anaphylactic reactions. Besides case histories and controlled food challenges, the detection of the IgE antibodies specific to cow’s milk allergens is important for the diagnosis of cow-milk-specific IgE sensitization. Cow´s milk allergen molecules provide useful information for the refined detection of cow-milk-specific IgE sensitization. Methods: A micro-array based on ImmunoCAP ISAC technology was developed and designated milk allergen micro-array (MAMA), containing a complete panel of purified natural and recombinant cow’s milk allergens (caseins, α-lactalbumin, β-lactoglobulin, bovine serum albumin-BSA and lactoferrin), recombinant BSA fragments, and α-casein-, α-lactalbumin- and β-lactoglobulin-derived synthetic peptides. Sera from 80 children with confirmed symptoms related to cow’s milk intake (without anaphylaxis: <i>n</i> = 39; anaphylaxis with a Sampson grade of 1–3: <i>n</i> = 21; and anaphylaxis with a Sampson grade of 4–5: <i>n</i> = 20) were studied. The alterations in the specific IgE levels were analyzed in a subgroup of eleven patients, i.e., five who did not and six who did acquire natural tolerance. Results: The use of MAMA allowed a component-resolved diagnosis of IgE sensitization in each of the children suffering from cow’s-milk-related anaphylaxis according to Sampson grades 1–5 requiring only 20–30 microliters of serum. IgE sensitization to caseins and casein-derived peptides was found in each of the children with Sampson grades of 4–5. Among the grade 1–3 patients, nine patients showed negative reactivity to caseins but showed IgE reactivity to alpha-lactalbumin (<i>n</i> = 7) or beta-lactoglobulin (<i>n</i> = 2). For certain children, an IgE sensitization to cryptic peptide epitopes without detectable allergen-specific IgE was found. Twenty-four children with cow-milk-specific anaphylaxis showed additional IgE sensitizations to BSA, but they were all sensitized to either caseins, alpha-lactalbumin, or beta-lactoglobulin. A total of 17 of the 39 children without anaphylaxis lacked specific IgE reactivity to any of the tested components. The children developing tolerance showed a reduction in allergen and/or peptide-specific IgE levels, whereas those remaining sensitive did not. Conclusions: The use of MAMA allows for the detection, using only a few microliters of serum, of IgE sensitization to multiple cow’s milk allergens and allergen-derived peptides in cow-milk-allergic children with cow-milk-related anaphylaxis. |
| first_indexed | 2024-03-11T03:25:26Z |
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| language | English |
| last_indexed | 2024-03-11T03:25:26Z |
| publishDate | 2023-05-01 |
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| series | Nutrients |
| spelling | doaj.art-642cd8e71ba54a848dc55e120609103e2023-11-18T02:45:53ZengMDPI AGNutrients2072-66432023-05-011510240110.3390/nu15102401Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE SensitizationVictoria Garib0Daria Trifonova1Raphaela Freidl2Birgit Linhart3Thomas Schlederer4Nikolaos Douladiris5Alexander Pampura6Daria Dolotova7Tatiana Lepeshkova8Maia Gotua9Evgeniy Varlamov10Evgeny Beltyukov11Veronika Naumova12Styliani Taka13Alina Kiyamova14Stefani Katsamaki15Alexander Karaulov16Rudolf Valenta17Center for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, AustriaCenter for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, AustriaCenter for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, AustriaCenter for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, AustriaCenter for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, AustriaAllergy Department, 2nd Pediatric Clinic, National & Kapodistrian University of Athens, 11527 Athens, GreeceDepartment of Allergology and Clinical Immunology, Research and Clinical Institute for Pediatrics Named after Yuri Veltischev at the Pirogov Russian National Research Medical University of the Russian Ministry of Health, 117997 Moscow, RussiaDepartment of Bioinformatics, Department of Pediatric Surgery, Pirogov Russian National Research Medical University of the Russian Ministry of Health, 117997 Moscow, RussiaDepartment of Faculty Therapy, Endocrinology, Allergology and Immunology, Ural State Medical University, 620028 Ekaterinburg, RussiaCenter of Allergy and Immunology, 123182 Tbilisi, GeorgiaDepartment of Allergology and Clinical Immunology, Research and Clinical Institute for Pediatrics Named after Yuri Veltischev at the Pirogov Russian National Research Medical University of the Russian Ministry of Health, 117997 Moscow, RussiaDepartment of Faculty Therapy, Endocrinology, Allergology and Immunology, Ural State Medical University, 620028 Ekaterinburg, RussiaDepartment of Faculty Therapy, Endocrinology, Allergology and Immunology, Ural State Medical University, 620028 Ekaterinburg, RussiaAllergy Department, 2nd Pediatric Clinic, National & Kapodistrian University of Athens, 11527 Athens, GreeceInternational Center of Molecular Allergology, Ministry of Innovation Development, Tashkent 100174, UzbekistanInternational Center of Molecular Allergology, Ministry of Innovation Development, Tashkent 100174, UzbekistanLaboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119991 Moscow, RussiaCenter for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, AustriaBackground: Immunoglobulin-E(IgE)-mediated hypersensitivity to cow’s milk allergens is a frequent cause of severe and life-threatening anaphylactic reactions. Besides case histories and controlled food challenges, the detection of the IgE antibodies specific to cow’s milk allergens is important for the diagnosis of cow-milk-specific IgE sensitization. Cow´s milk allergen molecules provide useful information for the refined detection of cow-milk-specific IgE sensitization. Methods: A micro-array based on ImmunoCAP ISAC technology was developed and designated milk allergen micro-array (MAMA), containing a complete panel of purified natural and recombinant cow’s milk allergens (caseins, α-lactalbumin, β-lactoglobulin, bovine serum albumin-BSA and lactoferrin), recombinant BSA fragments, and α-casein-, α-lactalbumin- and β-lactoglobulin-derived synthetic peptides. Sera from 80 children with confirmed symptoms related to cow’s milk intake (without anaphylaxis: <i>n</i> = 39; anaphylaxis with a Sampson grade of 1–3: <i>n</i> = 21; and anaphylaxis with a Sampson grade of 4–5: <i>n</i> = 20) were studied. The alterations in the specific IgE levels were analyzed in a subgroup of eleven patients, i.e., five who did not and six who did acquire natural tolerance. Results: The use of MAMA allowed a component-resolved diagnosis of IgE sensitization in each of the children suffering from cow’s-milk-related anaphylaxis according to Sampson grades 1–5 requiring only 20–30 microliters of serum. IgE sensitization to caseins and casein-derived peptides was found in each of the children with Sampson grades of 4–5. Among the grade 1–3 patients, nine patients showed negative reactivity to caseins but showed IgE reactivity to alpha-lactalbumin (<i>n</i> = 7) or beta-lactoglobulin (<i>n</i> = 2). For certain children, an IgE sensitization to cryptic peptide epitopes without detectable allergen-specific IgE was found. Twenty-four children with cow-milk-specific anaphylaxis showed additional IgE sensitizations to BSA, but they were all sensitized to either caseins, alpha-lactalbumin, or beta-lactoglobulin. A total of 17 of the 39 children without anaphylaxis lacked specific IgE reactivity to any of the tested components. The children developing tolerance showed a reduction in allergen and/or peptide-specific IgE levels, whereas those remaining sensitive did not. Conclusions: The use of MAMA allows for the detection, using only a few microliters of serum, of IgE sensitization to multiple cow’s milk allergens and allergen-derived peptides in cow-milk-allergic children with cow-milk-related anaphylaxis.https://www.mdpi.com/2072-6643/15/10/2401cow’s milk allergyallergen moleculesmilk allergen micro-arraypeptidesanaphylaxismilk tolerance |
| spellingShingle | Victoria Garib Daria Trifonova Raphaela Freidl Birgit Linhart Thomas Schlederer Nikolaos Douladiris Alexander Pampura Daria Dolotova Tatiana Lepeshkova Maia Gotua Evgeniy Varlamov Evgeny Beltyukov Veronika Naumova Styliani Taka Alina Kiyamova Stefani Katsamaki Alexander Karaulov Rudolf Valenta Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization Nutrients cow’s milk allergy allergen molecules milk allergen micro-array peptides anaphylaxis milk tolerance |
| title | Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization |
| title_full | Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization |
| title_fullStr | Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization |
| title_full_unstemmed | Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization |
| title_short | Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization |
| title_sort | milk allergen micro array mama for refined detection of cow s milk specific ige sensitization |
| topic | cow’s milk allergy allergen molecules milk allergen micro-array peptides anaphylaxis milk tolerance |
| url | https://www.mdpi.com/2072-6643/15/10/2401 |
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