Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cow-Milk-Allergic Patients, Sera and PBMC Samples
2.2. ImmunoCAP ISAC Measurements
2.3. Milk Allergen Micro-Array (MAMA)
2.4. Statistical Analyses
3. Results
3.1. Characterization of CM-Allergic Patients
3.2. Creation of MAMA
3.3. MAMA, but Not ImmunoCAP, or Skin Testing with CM Extracts Identifies all Patients with CMA According to a Sampson Score of 1–5
3.4. All CM-Allergic Patients with a Sampson Grade of 4–5 (but Bot Those with a Score of 1–3) Show Casein-Specific IgE Reactivity
3.5. The Use of MAMA Reveals IgE Reactivity to Cryptic Milk-Allergen-Derived Peptides
3.6. IgE Levels to CM Allergens and Allergen-Derived Peptides Are Higher in Patients with Anaphylactic Reactions to CM than in Patients without Anaphylactic Symptoms
3.7. CM-Allergic Patients Who Develop Tolerance after an Elimination Diet Show a Drop of Allergen-Specific IgE When Using MAMA
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
MAMA | Milk allergen micro-array |
CM | Cow´s milk |
CMA | Cow’s milk allergy |
BSA | Bovine serum albumin |
HSA | Human serum albumin |
AIT | Allergen-specific immunotherapy |
OIT | Oral immunotherapy |
GI | Gastrointestinal symptoms |
BA | Bronchial asthma |
AR | Allergic rhinitis |
AD | Atopic dermatitis |
FA | Food allergy |
SPT | Skin prick test |
MV | Median value |
ISU | ISAC standardized units |
ISU-E | IgE level presented in ISAC standardized units |
A4–5 | Patients with milk-related anaphylaxis with a Sampson score of 4–5 |
A1–3 | Patients with milk-related anaphylaxis with a Sampson score of 1–3 |
NA | Patients without anaphylaxis |
na-cas | natural alpha casein |
nALA | natural alpha lactalbumin |
nBLG | natural betalagtoglobulin |
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Patients | Number | Gender | Age | CM-Related Symptoms | SPT CM | Total IgE | sIgE to CM | Other Allergy |
---|---|---|---|---|---|---|---|---|
n % of total | f/m (%) | Years [Q1–Q3] (min–max) | Type: n | n | kU/L [Q1–Q3] (min–max), n | kUA/L [Q1–Q3] (min-max), n | Type: n | |
Total CM | 80 | 28/52 | MV: 3.1 | Skin: 62 | pos: 27 | MV: 99 | MV: 4.6 | BA: 18 |
allergic | 100% | (35/65%) | [2.0–5.5] | GI: 42 | neg: 6 | [34.1–649] | [0.9–24.3] | AR: 28 |
(0.5–12) | Sys: 41 | nd: 46 | (6.7–7372) n = 67 | (0–100) n = 57 | FA: 52 | |||
With anaphylaxis | 41 | 14/27 | MV: 5.0 | Skin: 29 | pos: 16 | MV: 212 | MV: 20.4 | BA: 12 |
51.25% | (34.2/65.8%) | [2.9–8.5] | GI: 20 | neg: 1 | [45.9–705] | [8–93.9] | AR: 18 | |
(1–12) | Sys: 41 | nd: 24 | (6.7–7372) n = 36 | (0.12–100) n = 26 | FA: 29 | |||
A4-5 | 20 | 7/13 | MV: 4.9 | Skin: 14 | pos: 3 | MV: 257.5 | MV: 46.6 | BA: 8 |
Sampson score 4-5 | 25% | (35/65%) | [2.9–8.8] | GI: 9 | neg: 0 | [95–791.3] | [20–98] | AR: 9 |
(2.3–12) | Sys: 20 | nd: 17 | (6.7–7372) n = 18 | (6–100) n = 12 | FA: 15 | |||
A1-3 | 21 | 7/14 | MV: 5.0 | Skin: 15 | pos: 13 | MV: 95 | MV: 13.3 | BA: 4 |
Sampson score 1-3 | 26.25% | (33.3/66.7%) | [2.5–8.5] | GI: 11 | neg: 1 | [43.3–699.3] | [2.1–46.1] | AR: 9 |
(1–11.2) | Sys: 21 | nd: 7 | (20.2–4030) n = 18 | (0.12–100) n = 14 | FA: 14 | |||
NA | 39 | 14/25 | MV: 2.5 | Skin: 33 | pos: 11 | MV: 68.5 | MV: 1.3 | BA: 6 |
Without | 48.75% | (35.9/64.1%) | [1.3–3.9] | GI: 22 | neg: 5 | [23.3–311] | [0.4–3.6] | AR: 10 |
anaphylaxis | (0.5–6) | Sys: 0 | nd: 22 | (7.5–1661) n = 31 | (0–100) n = 31 | FA: 23 |
Time | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Patient ID | Gender | Age (Months) | Difference (Months) | Tolerance Development | Tolerance to Milk | Symptoms | Eosinophils | Total IgE | ||
Severity | Other | % | ×109/L | (kU/L) | ||||||
1 | f | 34 | 18 | no | 5 | BA, AR, GI | 8 | 0.68 | 440 | |
1a | 52 | no | no | 5 | BA, AR, GI | 5 | 0.6 | 440 | ||
25 | m | 44 | 18 | no | 3 | AD, BA | 5 | 0.4 | 39.5 | |
25a | 62 | no | no | 3 | AD, BA | 5 | 0.4 | 39.5 | ||
65 | m | 72 | 9 | baked | 0 | AD, AR, GI | 6.3 | 0.42 | nd | |
65a | 81 | no | baked | 0 | AD, AR, GI | 6.3 | 0.42 | nd | ||
66 | m | 16 | 18 | baked | 0 | AD, AR, GI | 2 | 0.02 | 248.7 | |
66a | 34 | no | baked | 0 | AD, AR, GI | 2 | 0.13 | 127.8 | ||
11 | m | 58 | 11 | no | 4 | AD, AR, GI | 8 | 0.67 | nd | |
11a | 69 | no | no | 4 | AD, AR, GI | 5 | 0.4 | nd | ||
36 | f | 35 | 18 | no | 2 | AR, GI | 3.6 | 0.3 | 32.3 | |
36a | 53 | yes | baked | 0 | AR | 3.6 | 0.3 | 32.3 | ||
32 | m | 134 | 9 | no | 2 | AR, GI | 3.7 | 0.3 | 48.1 | |
32a | 143 | yes | baked | 0 | 0 | nd | nd | nd | ||
38 | f | 88 | 18 | no | 2 | AD, AR, GI | 3 | 0.2 | 82.5 | |
38a | 106 | yes | baked | 0 | 0 | nd | nd | nd | ||
67 | m | 30 | 18 | baked | 0 | AD, GI | 4 | 0.24 | 78.8 | |
67a | 48 | yes | fermented | 0 | AD | 4.6 | 0.3 | 58.6 | ||
70 | m | 67 | 12 | baked | 0 | AD, BA, AR, GI | 8.8 | 1 | nd | |
70a | 79 | yes | fermented | 0 | BA, AR | 11.6 | 1.27 | nd | ||
30 | m | 21 | 8 | no | 3 | AD, GI | 8 | 0.68 | nd | |
30a | 29 | yes | baked | 0 | AD | 3.2 | 0.3 | nd |
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Garib, V.; Trifonova, D.; Freidl, R.; Linhart, B.; Schlederer, T.; Douladiris, N.; Pampura, A.; Dolotova, D.; Lepeshkova, T.; Gotua, M.; et al. Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization. Nutrients 2023, 15, 2401. https://doi.org/10.3390/nu15102401
Garib V, Trifonova D, Freidl R, Linhart B, Schlederer T, Douladiris N, Pampura A, Dolotova D, Lepeshkova T, Gotua M, et al. Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization. Nutrients. 2023; 15(10):2401. https://doi.org/10.3390/nu15102401
Chicago/Turabian StyleGarib, Victoria, Daria Trifonova, Raphaela Freidl, Birgit Linhart, Thomas Schlederer, Nikolaos Douladiris, Alexander Pampura, Daria Dolotova, Tatiana Lepeshkova, Maia Gotua, and et al. 2023. "Milk Allergen Micro-Array (MAMA) for Refined Detection of Cow’s-Milk-Specific IgE Sensitization" Nutrients 15, no. 10: 2401. https://doi.org/10.3390/nu15102401