ALEX³ Case #5

Eva, 19 years from North-Western Europe

Clinical history

Since late childhood: Allergic rhinitis caused by allergy to grass pollen and house dust mites. Eva’s mother has been advised to avoid peanuts and nuts during her pregnancy. Up to now, Eva has avoided both peanuts and nuts, but traces of these foods were not avoided in the past. As a child she experienced atopic dermatitis and was treated with asthma medication in case of airway infections until the age of 12.

Family history

Unknown

Present situation

Last year Eva visited a general practitioner (GP) because of stomachache and diarrhea after ingestion of an Asian dish. She asked the GP if allergy to peanuts could be the cause of her symptoms. Specific IgE tests (singleplex) were ordered by the GP which showed the following results …

Eva's results from IgE singleplex testing

Allergen source Allergen

Almond

Extract

Hazelnut

Extract

Peanut

Extract

Coconut

Extract

Brazil nut

Extract

Allergen source Biochemical designation

Almond

x

Hazelnut

x

Peanut

x

Coconut

x

Brazil nut

x

Allergen source IgE Level [kUA/L]

Almond

67.0

Hazelnut

33.2

Peanut

21.1

Coconut

6.6

Brazil nut

0.74

  • The patient was then referred to an allergologist, who repeated the in vitro tests (January 2019) with the same outcome.
  • Skin prick tests were performed and showed positive results for grass pollen and house dust mites. Prick to Prick tests with fresh nuts – almond, brazil nut, cashew, hazelnut, macadamia, pecan nut, peanut and pistachio – showed negative results.
  • Provocation testing with peanut (open oral food challenge) also showed a negative result.
  • An ALEX test was requested to re-evaluate the specific IgE tests from December 2018 and January 2019

Eva's ALEX results with and without CCD blocking

Allergen source Allergen

Bahia grass

Extract

Timothy grass

Phl p 1

Bermuda grass

Cyn d 1

Common reed

Extract

Cultivated rye pollen

Extract

Maize pollen

Zea m 1

Allergen source ALEX without CCD blocking (kUA/L)

Bahia grass

11.33

Timothy grass

9.03

Bermuda grass

7.67

Common reed

9.57

Cultivated rye pollen

17.79

Maize pollen

11.73

Allergen source ALEX with CCD blocking (kUA/L)

Bahia grass

≤ 0.10

Timothy grass

9.02

Bermuda grass

7.71

Common reed

≤ 0.10

Cultivated rye pollen

0.51

Maize pollen

≤ 0.10

Allergen source Allergen

Oat

Extract

Quinoa

Extract

Buckwheat

Extract

Barley

Extract

Lupine seed

Extract

Millet

Extract

Cultivated rye, flour

Extract

Spelt

Extract

Corn, cereal

Extract

Allergen source ALEX without CCD blocking (kUA/L)

Oat

1.43

Quinoa

8.22

Buckwheat

9.93

Barley

5.06

Lupine seed

2.09

Millet

10.32

Cultivated rye, flour

3.64

Spelt

0.61

Corn, cereal

0.40

Allergen source ALEX with CCD blocking (kUA/L)

Oat

≤ 0.10

Quinoa

≤ 0.10

Buckwheat

≤ 0.10

Barley

≤ 0.10

Lupine seed

≤ 0.10

Millet

≤ 0.10

Cultivated rye, flour

≤ 0.10

Spelt

≤ 0.10

Corn, cereal

≤ 0.10

Allergen source Allergen

Cashew

Ana o 1

Cashew

Ana o 3

Pecan

Extrakt

Pecan

Car i 1

Hazelnut

Cor a 9

Hazelnut

Cor a 11

Walnut

Extract

Walnut

Jug r 4

Allergen source ALEX without CCD blocking (kUA/L)

Cashew

0.78

Cashew

1.32

Pecan

6.04

Pecan

4.87

Hazelnut

3.27

Hazelnut

3.54

Walnut

2.41

Walnut

9.83

Allergen source ALEX with CCD blocking (kUA/L)

Cashew

≤ 0.10

Cashew

≤ 0.10

Pecan

≤ 0.10

Pecan

≤ 0.10

Hazelnut

≤ 0.10

Hazelnut

≤ 0.10

Walnut

≤ 0.10

Walnut

≤ 0.10

Allergen source Allergen

Macadamia

Extract

Pistachio

Pis v 2

Pistachio

Pis v 3

Almond

Extract

Hom s LF

CCD marker

Allergen source ALEX without CCD blocking (kUA/L)

Macadamia

1.25

Pistachio

2.09

Pistachio

1.04

Almond

2.36

Hom s LF

17.13

Allergen source ALEX with CCD blocking (kUA/L)

Macadamia

≤ 0.10

Pistachio

≤ 0.10

Pistachio

≤ 0.10

Almond

≤ 0.10

Hom s LF

≤ 0.10

Summary

  • Extract-based IgE tests showed strong reactivity to multiple nuts and legumes, but skin-prick and provocation tests were negative
  • ALEX³ revealed high CCD marker (17.13 kUA/L) and loss of all food-specific signals after CCD blocking, confirming false-positive extract results
  • Only true grass pollen sensitisation (Phl p 1, Phl p 2, Cyn d 1) remained clinically relevant
  • Extracts and purified components (plant based, hymenoptera, mussles) contain CCD epitopes
  • Eva’s gastrointestinal symptoms were non-allergic; dietary restrictions are unnecessary

Novel findings revealed by ALEX³

  • The CCD blocking of the ALEX³ test dramatically reduces the number of falsely elevated results from 110 to 10.
  • The interpretative burden for the physician has been substantially decreased by blocking CCD specific antibodies.
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