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Possible anaphylaxis to blueberry: potential cross-reactivity with other berries

Question:

Reviewed 2/14/2018

8/29/2012
Is there any known cross reactivity amongst true berries (blueberries, blackberries, raspberries as opposed to strawberries)? I have not read such (not much data either way). Recently I saw a new patient with a history plausible for blackberry allergy (10 yrs ago, avoiding) and now blueberries. (serum testing pending, patient on a betablocker as well as antihistamines, so I did not skin test). Thanks for any advice.

Answer:

Thank you for your inquiry.

First of all, you are correct in that there is very little, if any, information available regarding potential allergenic cross-reactivity between "berries." You mentioned blueberries, blackberries, raspberries, and strawberries, with special reference to blackberries and blueberries. Therefore I will try and answer your question by discussing each separately.

First of all, blackberries:
The blackberry is a member of the Rosaceae family. There have been two reports of anaphylaxis to blackberry (1, 2; Reference 2 is in the form of a full abstract). Both reports were from the same group. Of note is that the suspected allergen in each report was neither lipid transfer proteins nor proteins from the Bet v 1 family. As you will see later, this distinguishes the allergen putatively responsible for anaphylaxis to blackberry from that which has been reported to blueberry. Thus there is, to the best of my knowledge, no known cross-reactivity between these two berries.

It would be expected for blackberry to cross-react with other members of the Rosaceae family (apple, almond, apricot, cloudberry, dewberry, raspberry, et cetera). However, no such cross-reactivity, to the best of my knowledge, has been demonstrated to date. In addition, in Scott Sicherer's superb article on food cross-reactions (3), there is no mention of any cross-reactivity between any form of berries.

Next, blueberries:
Blueberries are members of the Ericaceae family. There is, to my knowledge, only one reported case of allergy to blueberries (4). In this instance, the allergen putatively responsible was a 10 kDa lipid transfer protein similar to those that have been previously identified as major fruit allergens, especially in the Mediterranean area. Thus, as noted above, the allergen in blueberry was distinct from that reported in the case of anaphylaxis to blackberry.

Raspberries:
Raspberry is also a member of the Rosaceae family. Raspberries contain several known allergens. They do contain both a Bet v 1 homologue (RUB i 1) and a lipid transfer protein (RUB i 3). The potential cross-reactivity between raspberry, blackberry, and strawberry is complex. Cross reactivity probably does exist (5 - in form of a complete abstract copied below).

Strawberries:
Strawberries are also members of the Rosaceae family. Strawberries do contain a Bet v 1 homologue, a lipid transfer protein, and profilin.

There is potential cross-reactivity between strawberries and other members of the Rosaceae family, but no clear-cut cross-reactivity has been demonstrated with blueberry to my knowledge.

As you know, there are several reports of allergic reactions to strawberries.

In summary, speaking more directly to your case, to the best of my knowledge, there is no known cross-reactivity between blackberry and blueberry, and there are very few cases of anaphylaxis reported to either of these berries. More extensive cross-reactivity has been reported for raspberry with other berries.

However, in terms of blueberries and blackberries, as mentioned earlier, these data have to be interpreted with caution because there are very few studies of the cross-reactivity between these berries, probably because of the few case reports.

Thank you again for your inquiry and we hope this response is helpful to you.

References:

Armentia A, Lombardero M, Barber D, Callejo A, Vega J, Martínez C, Rebollo S. Blackberry (Morus nigra) anaphylaxis. Alergol Inmunol Clin 1999;14(6):398-401.

Ann Allergy Asthma Immunol. 2001 Jul;87(1):54-9.
Anaphylaxis associated with antiphospholipid syndrome
Armentia A, Barber D, Lombardero M, Martín Santos JM, Martin Gil FJ, Arranz Peña ML, Callejo A, Salcedo G, Sánchez-Monge R.
Source
Allergy Section, Hospital Universitario Rio Hortega, Valladolid, Spain.
Abstract
Background: To our knowledge, no previously published reports have described food-induced anaphylaxis associated with the antiphospholipid syndrome.
Objective: We undertook a study of four patients with thrombosis associated with the antiphospholipid syndrome after each patient experienced anaphylaxis attributable to ingestion of vegetal foods.
Methods: IgE antibody levels to various foods were determined in serum specimens from the study patients, and skin prick tests with the same allergens were conducted to determine their in vivo responses. Hematologic, cardiopulmonary, vascular, and rheumatologic studies were also performed. IgG anticardiolipin antibody levels were determined by ELISA.
Results: All four patients fulfilled the criteria for antiphospholipid syndrome and had high levels of specific IgE antibodies for certain food allergens. By immunoblot analysis, the presence of serum IgE specific for a 45-kD protein band in an almond extract was detected in these four patients who experienced food-related anaphylaxis. No specific IgE was detected in sera from normal subjects. No IgE antibodies specific for the food panallergen lipid transfer proteins were detected.
Conclusions: This is the first report of severe food-precipitated anaphylaxis associated with the antiphospholipid syndrome and the first description of a patient with allergy to blackberry. The possible involvement of food panallergens distinct from lipid transfer proteins is also discussed

Sicherer S: Clinical implications of cross-reactive food allergens
Journal of Allergy and Clinical Immunology Vol. 108, Issue 6, Pages 881-890, 2001.
Gebhardt C, Vieths S, Gubesch M, Averbeck M, Simon JC, Treudler R. Allergy. 2009 Mar;64(3):498-9. Epub 2009 Feb 12. Allergy. 2009 Mar;64(3):498-9. Epub 2009 Feb 12. 10 kDa lipid transfer protein: the main allergenic structure in a German patient with anaphylaxis to blueberry.
Biofactors. 2008;34(1):37-46.
Screening and identification of putative allergens in berry fruits of the Rosaceae family: technical challenges.

Marzban G, Maghuly F, Herndl A, Katinger H, Laimer M.
Source
Plant Biotechnology Unit, Institute of Applied Microbiology, Department of Biotechnology, BOKU, Vienna, Austria.
Abstract
Cross-reactive proteins in small fruits of the Rosaceae family like strawberry, raspberry and blackberry revealed an unexpected complex IgE-reactivity pattern. Several copies of PR-10 and PR-14 proteins were detected by Southern blots in strawberry, raspberry and blackberry. In raspberry, the highest similarity at the DNA level for PR-10 and PR-14 (Rub i 1 and Rub i 3) was detected to strawberry sequences of Fra a 1 and Fra a 3. At the protein level, Rub i 1 and Rub i 3 showed more than 70% identity with homologous proteins of rosaceous fruits. Furthermore, raspberries contained additional putative allergens, e.g. class III acidic chitinases and cyclophilins. Blackberries were shown to share at least two well-known major fruit allergens with other rosaceous fruits, namely PR-10s and PR-14s homologous proteins. However the IgE-reactive proteins of small fruits are still not extensively investigated. The main challenges in studying small fruit allergens are the complexity of the fruit matrix, the diversity of physico-chemical properties of fruit proteins, the lack of appropriate protein extraction procedures and the missing information about the influence of processing treatments on food components.

Sincerely,
Phil Lieberman, M.D.