Ask The Expert
May 11, 2015
Allergen-component Diagnostics Food-pollen Allergy
Question
We are encouraged to utilize allergen-component diagnostics for food-pollen allergy in order to guide advice. But these tests are expensive in our country. What is the minimum test profile you would recommend to identify PR-10, profilin, and LTP components. For example, would Pru p 1,3 and 4 be sufficient?
Answer
By Professor Anna Pomes
Patterns of sensitization to PR--‐10, profiling and lipid transfer protein (LTP) allergens show a wide geographical variability, depending on the exposure to pollens and ingested foods in each particular area. The minimum test profile to identify sensitivities to these three groups of proteins in component--‐resolved diagnosis (CRD) should be selected according to the patterns of sensitization to these allergens in that specific country.
Two main patterns of sensitization to PR--‐10, profilins and LTPs have been well described in Europe (1, 2). In northern and central areas, allergies to Rosaceae fruits, Apiaceae vegetables and hazelnut are associated with birch pollinosis, and patients present with mild oropharyngeal symptoms known as oral allergy syndrome (OAS). The allergens responsible for this pollen--‐food cross--‐reactivity are Bet v 1 and pollen profilins, whose sensitivity to pepsin digestion explains the restriction of symptoms to the oral cavity. In contrast, in areas of southern Europe free of birch pollen exposure, peach (Pru p allergens) and certain pollens, such as those from mugwort and plane tree, might contribute to sensitization to LTPs. These are very stable proteins, resistant to digestion, and associated with consequent systemic reactions, that are often severe. One might anticipate that testing for IgE reactivity to only birch and peach allergens would allow distinguishing between both patterns of sensitization. A strong reactivity to Bet v 1 (PR--‐10) could indicate the possibility of mostly mild reactions to cross--‐reacting foods (i.e. apple), but also serious reactions to cross--‐reacting allergens from peanut, hazelnut, celery and soybean (3). On the contrary, a confirmed sensitization to the LTP Pru p 3, considered a primary sensitizer and marker of reactivity to LTPs from the Rosaceae family, combined with a lack of IgE to Bet v 1, would be an indicator of a possible development of systemic reactions to LTPs.
Unfortunately, polysensitization to additional allergens from plants and pollens, even from distantly related botanical species, occurs, and can influence the IgE reactivity to these three groups of allergens in specific areas. Even within the same country, several patterns of sensitization have been described (i.e. to LTPs, profilins) (4, 5). There is a low positive predictive value of skin prick test in diagnosis of fruit and pollen allergies, precisely due to the cross--‐reactivity among allergens from different species. Ideally, allergens should be classified in groups or clusters of cross--‐reactive molecules. A minimum set of at least one representative allergen from each cluster, relevant to the patients from the country in question, should be selected for CRD. This strategy would assure that most relevant cross--‐reactivities for that area would be covered in the test. A multicenter study illustrated this approach by classifying LTPs into cross--‐reactive groups, depending on their IgE reactivities in microarrays (6). This analysis confirmed several non--‐cross--‐reactive LTPs (such as Pha v 3, Par j 1, Ole e 7, Tri a 14 and Lac s 1), in agreement with known routine clinical observations (4, 6). The addition of these allergens to the test would increase the diagnostic potential of CRD, especially for patients showing a clinical history of reactivity to any of them, or if those allergens are important sensitizers in that specific area (i.e. allergens associated with olive pollinosis in southern Spain). Even minor allergens should be 2 included in certain cases, such as Ole e 7, which is a clinically relevant marker of olive allergy due to its associated risk of asthma (4). In Iran, a poor predictive value of sequence homology for profilins cross--‐ reactivity has been observed, illustrated by a lack of clinical reactivity to watermelon among most melon allergic patients (7). In this case, the addition of profilins from both sources in CRD would be advised. Although the symptoms induced by profilins tend to be mild, strong reactions have been described against profilins from melon, banana, tomato and/or citrus fruits (3). The use of these fruits as markers of profiling sensitization would be recommended in certain areas. Profilins have also been described as markers of severity for grass allergy sensitization (4).
Yet not all the reactivities detected by in vitro CRD are clinically relevant. CRD is meant to complement in vivo assays, hopefully by increasing their sensitivity and/or specificity, and by informing about the molecule/s causing sensitization and the patient--‐specific IgE reactivity profiles (2, 3). Algorithms have been suggested to correctly diagnose these complex allergies, by combining in vivo and in vitro tests (3, 5). Representative molecules from cross--‐reactive groups of allergens, which will differ with the geographical areas, should be selected for CRD analysis. The use of arrays or multiplex technologies, instead of individual allergen tests, may also contribute to cost reduction in the long term, using small amounts of sera. The selection of the minimum set of allergens to be used for component resolved diagnosis should result from a careful analysis of sensitization patterns in that particular country.
- Fernandez--‐Rivas M1, Bolhaar S, Gonzalez--‐Mancebo E, Asero R, van Leeuwen A, Bohle B, Ma Y, Ebner C, Rigby N, Sancho AI, Miles S, Zuidmeer L, Knulst A, Breiteneder H, Mills C, Hoffmann--‐Sommergruber K, van Ree R. Apple allergy across Europe: how allergen sensitization profiles determine the clinical expression of allergies to plant foods. J Allergy Clin Immunol. 2006; 118(2):481--‐8.
- 2- Ballmer--‐Weber BK, SkamstrupnHansen K, Sastre J, Andersson K, Bätscher I, Ostling J, Dahl L, Hanschmann KM, Holzhauser T, Poulsen LK, Lidholm J, Vieths S. Component--‐resolved in vitro diagnosis of carrot allergy in three different regions of Europe. Allergy. 2012; 67(6):758--‐66.
- 3- Asero R. Plant food allergies: a suggested approach to allergen--‐resolved diagnosis in the clinical practice by identifying easily available sensitization markers. Int Arch Allergy Immunol. 2005; 138(1):1--‐11.
- Barber D, de la Torre F, Feo F, Florido F, Guardia P, Moreno C, Quiralte J, Lombardero M, Villalba M, Salcedo G, Rodríguez R. Understanding patient sensitization profiles in complex pollen areas: a molecular epidemiological study. Allergy. 2008; 63(11):1550--‐8.
- Barber D, de la Torre F, Lombardero M, Antépara I, Colas C, Dávila I, Tabar AI, Vidal C, Villalba M, Salcedo G, Rodríguez R. Component--‐resolved diagnosis of pollen Allergy based on skin testing with profilin, polcalcin and lipid transfer protein pan--‐allergens. Clin Exp Allergy. 2009; 39(11):1764--‐73.
- Palacín A, Gomez--‐Casado C, Rivas LA, Aguirre J, Tordesillas L, Bartra J, Blanco C, Carrillo T, Cuesta--‐ Herranz J, de Frutos C, Alvarez--‐Eire GG, Fernández FJ, Gamboa P, Muñoz R, Sanchez--‐Monge R, Sirvent S, Torres MJ, Varela--‐Losada S, Rodríguez R, Parro V, Blanca M, Salcedo G, Diaz--‐Perales A. Graph based study of allergen cross--‐reactivity of plant lipid transfer proteins (LTPs) using microarray in a multicenter study. PLoS One. 2012; 7(12):e50799.
- Sankian M, Varasteh A, Pazouki N, Mahmoudi M. Sequence homology: a poor predictive value for profilins cross--‐reactivity. Clin Mol Allergy. 2005; 10; 3:13.
Anna Pomes, PhD, FAAAAI
Research Director
INDOOR Biotechnologies, Inc.
Charlottesville, VA, USA
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