Secondary soy allergy in children with birch pollen allergy may cause both chronic and acute symptoms.

Pediatr Allergy Immunol. 2012 Mar;23(2):117-23.


De Swert LF, Gadisseur R, Sjölander S, Raes M, Leus J, Van Hoeyveld E.

Pediatric Allergy, Department of Pediatrics, University Hospital Gasthuisberg, Leuven, Belgium.




Secondary soy allergy occurring in tree pollen allergic patients may cause acute symptoms.


We selected children with birch pollen allergy suspected of also being soy allergic (SA). Soy allergy was proven based on one of the following: (i) a clear-cut clinical history; (ii) a positive provocation test; and (iii) elimination and reintroduction of soy. Skin prick tests (SPT) were performed with a commercial soy extract and with soy flour. Specific IgE to Gly m 4, Gly m 5, and Gly m 6 was determined by means of ImmunoCAP and ISAC. Eight soy-tolerant atopic children being CAP rGly m 4-negative served as a control group for skin testing.


Of 15 subjects with birch pollen allergy and being suspected of soy allergy, eight of them proved to be SA; 7/15 subjects proved to be soy tolerant (ST). Besides acute symptoms in 8/8 SA subjects, 3/8 subjects also had been suffering from severe chronic complaints because of soy allergy. SPT with commercial soy extract was negative in all SA and ST subjects tested. SPT with soy flour was positive in 8/8 SA and in 5/6 ST subjects, but negative in all 8 controls (p < 0.0001); the median weal diameter was 7.7 mm in SA subjects, compared to 3 mm in ST subjects (p < 0.01). The median IgE level to rGly m 4 using CAP and ISAC was, respectively, 32.4 kU/l and 4.0 ISU in SA subjects, compared to 6.2 kU/l and 0.4 ISU in ST subjects (p < 0.05). Analysis of IgE to nGly m 5 and nGly m 6, using CAP or ISAC, showed no significant differences between SA and ST subjects.


Secondary soy allergy may cause severe chronic besides acute symptoms. SPT with soy flour is a sensitive and specific tool in detecting soy sensitization. SPT with soy flour, CAP rGly m 4, and ISAC rGLY m 4 are valuable tools in the diagnosis of birch-pollen-associated secondary soy allergy.

© 2011 John Wiley & Sons A/S.

PMID: 22017341



Birch pollen allergic patients may develop secondary food allergy, as a consequence of specific IgE cross-reactivity with Bet v 1, the major birch pollen allergen, and its homologues in fruits/vegetables (1,2). The allergens involved in this cross-reactivity belong to the PR-10 family, which are heat and digestion labile proteins. The symptoms experienced by birch pollen allergic patients on ingestion of Bet v 1 homologues in plant food typically occur within minutes after ingestion and mostly are restricted to complaints of oral allergy syndrome (OAS). Secondary soy allergy may develop in birch pollen allergic patients and has been shown to elicit acute symptoms, which may vary from mild to severe (3,4). Gly m 4 is the soy allergen involved in those cases.

Secondary plant food allergy is mainly a diagnosis based on history taking and clinical examination, for mainly 2 reasons: 1) the typical clinical picture with acute onset of symptoms within minutes after ingestion of the culprit food; 2) the fact that a substantial proportion of birch pollen allergic patients shows IgE-responses to PR-10 allergens of plant food without having clinical reactions to those foods (= sensitisation). Also among birch pollen allergic patients with positive IgE-responses to Gly m 4, only 10 % of those patients report clinical soy allergy (4).

We have studied 15 birch pollen allergic children and we documented secondary soy allergy in eight of them (5).  We have shown that secondary soy allergy may be the cause of severe chronic symptoms, besides acute symptoms (Fig 1). Indeed, three out of eight subjects had been suffering from severe generalized itching and recurrent urticaria, generalized atopic dermatitis and/or chronic diarrhea.  All these symptoms subsided on the sole withdrawal of soy from the diet.

This study documents that PR-10 proteins, involved in IgE cross-reactivity with pollen and plant food, can cause more than just OAS.

We also showed that skin prick test (SPT) with soy flour, CAP rGly m 4 and ISAC rGly m 4 are valuable tools in the diagnosis of birch-pollen-associated secondary soy allergy. SPT with soy flour at cut-off 7 mm weal diameter and CAP rGly m 4 at cut-off 17.6 kU/L both provided a specificity of 100 % for the diagnosis of secondary soy allergy, while the sensitivity was 75 % (5).

Impact of this study: in birch pollen allergic patients we should be aware of the possibility of secondary soy allergy as a cause of both, chronic and acute symptoms. SPT with soy flour and CAP rGly m 4 at specific cut-off are valuable tools in discriminating between soy sensitisation and clinical allergy to soy.


  1. Ebner C, Hirschwehr R, Radauer L,      Breiteneder H, Valenta R, Ebner H et al. Identification of allergens in      fruits and vegetables: IgE-cross-reactivities with the important birch      pollen allergens Bet v 1 and Bet v 2 (birch profilin). J Allergy Clin lmmunol 1995;95:962-9
  2. Fernandez-Rivas M, Bolhaar S, Gonzalez-Mancebo E, Asero R, van Leeuwen A, Bohle B et al. Apple allergy across Europe: how allergen sensitization profiles determine the clinical expression of allergies to plant foods. J Allergy Clin lmmunol 2006;118: 481-8
  3. Kleine-Tebbe J, Wangorsch A, Vogel L, Crowell DN, Haustein UF, Vieths S. Severe oral allergy syndrome and anaphylactic reactions caused by a Bet v 1-related PR-10 protein in soybean, SAM22. J Allergy Clin Immunol 2002: 110: 797–804.
  4. Mittag D, Vieths S, Vogel L et al. Soybean allergy in patients allergic to birch pollen: clinical investigation and molecular characterization of allergens. J Allergy Clin Immunol 2004: 113: 148–54.
  5. De Swert LFA. Gadisseur R. Sjölander S, Raes M, Leus J, Van Hoeyveld E. Secondary soy allergy in children with birch pollen allergy may cause both chronic and acute symptoms. Pediatric Allergy Immunol 2012;23:117-23.