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Food allergy in Europe André Knulst, Dept. Dermatology/Allergology
UMC Utrecht
Overview of the presentation
• Prevalence of peanut and soy allergy in Europe
• Sensitisation patterns in Europe
• Ranking of sensitisation to specific food allergens
• Crossreactivities
• Specific allergens and severity
• Thresholds for different foods
• News about soy
• Conclusions
Point prevalence of FC positive
peanut allergy
Region-stratified pooled prevalence of peanut allergy (PA) in studies published in Europe between January 2000 and September 2012. Markers represent percentages and 95%CI and boxes represent the size of the study (Nwaru et al, 2015)
.
.
.
Overall (I-squared = 92.9%, p = 0.000)
Gelencik (ref. 28)
Hourihane (ref. 31)
Venter (ref. 77)
Northern Europe
Nicolaou (ref. 48)
Grundy (ref. 29)
Southern Europe
Venter (ref. 74)
Kjaer (ref. 22)
Subtotal (I-squared = 12.2%, p = 0.336)
Lack (ref. 64)
Subtotal (I-squared = 0.0%, p = 1.000)
Orhan (ref. 50)
Osterballe (ref. 56)
Osterballe (ref. 56)
Osterballe (ref. 55)
Kristinsdottir (ref. 38)
Western Europe
Subtotal (I-squared = 74.5%, p = 0.001)
Study
0.22 (0.16, 0.28)
Percentage (95% CI)
0.00 (0.00, 0.10)
1.40 (0.80, 2.30)
0.30 (0.10, 1.00)
0.80 (0.40, 1.50)
0.60 (0.30, 1.30)
0.30 (0.10, 1.00)
0.50 (0.10, 1.80)
0.33 (0.12, 0.54)
0.20 (0.10, 0.30)
0.00 (-0.05, 0.05)
0.00 (0.00, 0.10)
0.40 (0.20, 1.10)
0.20 (0.00, 1.20)
0.60 (0.30, 1.40)
0.10 (0.00, 0.50)
0.35 (0.25, 0.45)
.
Weight
100.00
6.33
4.13
5.51
7.36
5.26
10.07
100.00
71.40
100.00
0.00
23.34
12.12
21.02
33.44
100.00
%Cases/Participants
2/404
2/1341
5/843
1/486
4/936
8/1246
15/1072
23/12090
7/933
2/700
3/891
0/11816
0/2739
1 2 300
Point prevalence of FC positive
soy allergy
.
.
Overall (I-squared = 63.1%, p = 0.028)
Kristinsdottir (ref. 38)
Osterballe (ref. 55)
Western Europe
Osterballe (ref. 56)
Osterballe (ref. 56)
Roehr (ref. 71)
Northern Europe
Study
0.26 (0.07, 0.44)
0.50 (0.30, 1.10)
0.10 (0.00, 0.70)
0.00 (0.00, 0.80)
0.00 (0.00, 0.40)
0.50 (0.20, 1.40)
ES (95% CI)
100.00
30.86
19.40
11.19
21.54
17.01
Weight
%Cases/Participants
7/1341
1/843
0/486
0/936
4/739
.5 1 1.5 20
Region-stratified pooled prevalence of soy allergy (SA) in studies published in Europe between January 2000 and September 2012. Markers represent percentages and 95%CI and boxes represent the size of the study (Nwaru et al, 2015)
Plant food protein families and risk of allergy
Source: ThermoFisher Scientific
Storage protein titers relatively high in NL
M. Blankestijn, Thematic poster session 14 EAACI 2015
Co-sensitisation PR-10 / other food allergens in adults
Animal origin: cow’s milk, hen’s egg, fish, shellfish
Apple allergy in Europe Impact of different allergens
Austria, Netherlands, Italy, Spain (n=400)
• Apple = Malus domesticus
• 4 major allergens
– Mal d 1 (PR10)→ mild symptoms – Northern Europe
– Mal d 2
– Mal d 3 (LTP)→ (50%) severe symptoms – Southern Europe
– Mal d 4
Kiwi allergy in Europe
Impact of CRD
• Severe symptoms: Iceland
• Mild symptoms: rest of Europe
• Recognition of allergens:
– Act d 8 (PR10): Western/Central and Eastern Europe: mild symptoms
– Act d 10 (LTP): Southern Europe: mild symptoms (in contrast to
apple!)
– Act d 1 (specific): Iceland: severe symptoms
Plant food protein families and risk of allergy
Source: ThermoFisher Scientific
EuroPrevall data: sensitization to hazelnut
Datema, J All Clin Immunol (2015)
EuroPrevall data: sensitization to hazelnut Cor a 1 most prevalent (74%)
Datema, J All Clin Immunol (2015)
EuroPrevall data: sensitization to hazelnut Cor a 8 mediterranean 83% Athens, 36% Madrid
Datema, J All Clin Immunol (2015)
EuroPrevall data: sensitization to hazelnut Cor a 9 and 14 <10% mainly children
Datema, J All Clin Immunol (2015)
Cor a 1 recognized by IgE among all the different subgroups
Masthoff J Allergy Clin Immunol 2013
IgE to nCor a 9 and Cor a 14 predictive for a hazelnut allergy with objective symptoms
Masthoff J Allergy Clin Immunol 2013
ROC curves peanut components in children (WKZ)
Otten et al. JACI 2012
• Weak correlation children: ρ = 0.17, P=0.01
• Moderate correlation adults: ρ = 0.52, P<0.001
Ara h 2 significantly correlated with
severity at population level Children Adults
Crossreactivity
Differences between subjective vs objective symptoms
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0,01 0,1 1 10 100 1000 10000 100000
Pro
bab
ility
Eliciting Dose (ED) peanut protein (mg)
Subjective symptoms
95% CI
Objective symptoms
95% CI
Klemans et al. CEA 2015
Small differences between children vs adults
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0,01 0,1 1 10 100 1000 10000 100000
Pro
bab
ility
Eliciting Dose (ED) peanut protein (mg)
Objective symptoms
Adults
95% CI
Children
95% CI
Klemans et al. CEA 2015
Verhoeckx FCT 2015
Processing soy
Soy milk vs soy flour allergy
Klemans et al. Allergy, 2013
Diagnostic performance of soy allergens
AUC of all diagnostic tests in the challenged population (n=30)
Diagnostic test AUC (95% CI)
Gly m 2S albumin 0.79 (0.62 – 0.96)
Gly m 4 0.54 (0.32 – 0.77)
Gly m 5 0.74 (0.54 – 0.94)
Gly m 6 0.77 (0.58 – 0.96)
Soy extract 0.77 (0.57 – 0.97)
SPT (n = 40) 0.76 (0.57 – 0.96)
CI, confidence interval
Klemans et al. Allergy, 2013
Allergenicity related to apple cultivar
Bolhaar et al. JACI 2005
Patient
Sex (Male/
Female)
Age (years)
Shrimp history Muller
0.01 g (2,16 mg)
0.1 g (21,6 mg)
1 g (216 mg)
7.5 g (1,62 g)
10 g (2,16 g)
30 g (6,48 g)
60 g (12,96 g)
Mealworm challenge
Muller
19 F 46 2 OA, S, GI 2
21 F 23 3 OA,S,R OA,S,GI OA, S, GI,R 3
22 M 69 1 OA OA OA, S 0
23 M 45 4 S, GI 2
24 F 27 4 OA OA OA, S 1
25 M 19 4 S GI 2
28 F 60 0 S S 1
31 M 30 3 GI 2
32 M 27 1 Neg
33 F 47 4 S S, R S, GI,R 3
34 F 52 4 Neg
36 M 26 4 S, GI 2
37 M 34 2 OA OA OA 0
38 F 23 3 OA, S OA OA OA, S 1
40 M 46 3 OA OA OA OA,GI 2
Novel foods: lessons from mealworm 13 out of 15 shrimp allergic patients react to mealworm
OA Oral allergy, local S Skin/mucosa GI Gastrointestinal R Respiratory C Cardiovascular Dose not given
Conclusions
• Sensitisation is related to the risk of allergy and severity
only on population level
• Age/geographical differences in the relevant allergens
• Crossreactivities are important (inhalant-food, food-food)
• Soy has moderate allergenic potential as compared to
other plant foods (influenced by processing)
• New protein sources need careful allergenic risk
assessment
• SPT and BAT can be important tools in the evaluation of
potential allergenicity