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Background Mechanisms that govern priming and degranulation of human mast cells (MCs) remain elusive. Besides, most of our knowledge is based on experiments from which data only reflect an average of all stimulated cells. This study aims at investigating the effects of proinflammatory cytokines IL-6, IL-33, and TNF-α on IgE-dependent and IgE-independent activation of individual MCs. Methods MCs were derived from CD34+ progenitors isolated from 50 mL whole blood from 4 healthy controls and 5 birch pollen allergic patients. Passively sensitized MCs were preincubated with IL-6, IL-33, or TNF-α and stimulated with anti-IgE/birch pollen allergen or substance P, the latter being a ligand for the G-protein-coupled MRGPRX2-receptor. Activationi.e., upregulation of CD203cand anaphylactic degranulationi.e., appearance of CD63were measured using flow cytometry. Results Preincubation with IL-33 demonstrated upregulated CD203c density without degranulation. Subsequent IgE-dependent stimulation (anti-IgE/birch pollen allergen) resulted in higher appearance of CD63 as compared to cells without preincubation, indicating IL-33 to exert a priming effect (P = 0.04). IL-6 only increased allergen-specific responses but to a lesser extent than IL-33. Combination of IL-33/IL-6 had a synergistic effect, demonstrating more degranulation in response to allergen. TNF-α had no effect on IgE-mediated activation, nor synergistic effects with IL-33. Stimulation with substance P resulted in degranulation that could not be enhanced by preincubation. Conclusions In conclusion, IL-33, and in a lesser extent IL-6, prime individual MCs for subsequent IgE-mediated activation. Moreover, this priming effect is synergistic. In contrast, none of the cytokines had a priming effect on MRGPRX2-mediated activation of MCs.

Background Mast cell progenitor cells, derived from CD34+ hematopoietic stem cells, enter the circulation and subsequently mucosal or connective tissues where they mature to mast cells. Upon activation, mast cells increase the expression of activation markers, e.g. CD63, and release histamine amongst other mediators. Traditionally, release of these mediators is quantified using assays measuring their extracellular concentration in the supernatant of stimulated cells. Methods Human mast cells (HuMC) were cultured from peripheral blood, phenotypically characterized, passively sensitized with allogenic IgE antibodies and finally stimulated by anti-IgE that crosslinks IgE/FcεRI complexes. Alterations in the number of cells positive for CD63 and release of histamine were quantified simultaneously by flow cytometry. Results In culture, two distinct CD45+ cell populations were identified: CD117+CD203c+hi and CD117-CD203c+low cells. Both populations showed positivity for FcεRI, tryptase and chymase, and contained histamine. Activation resulted in a significant increase of cells positive for CD63+ up to 21% (range: 1139) for CD117+CD203c+hi cells (P = 0.005), and 27% (1855) CD63+ for CD117-CD203c+low cells (P = 0.02). Baseline histamine content was higher for CD117+CD203c+hi cells than for CD117-CD203c+low cells, respectively 994 (6956815) Molecules of Equivalent Specific Fluorochrome V500 per cell (MESF-V500/cell) and 797 (6294978) MESF-V500/cell (P = 0.02). After activation, CD117+CD203c+hi cells showed significant histamine release of 578 (3661521) MESF-V500/cell, whilst CD117-CD203c+low cells resulted in 310 (217366) MESF-V500/cell histamine release. Conclusion This study discloses that culturing HuMC from CD34+ progenitors yields 2 phenotypically distinct cell populations that display a greatly similar response upon cross-linking of IgE/FcεRI complexes.

Marihuana allergy seems on the rise and has been attributed to a sensitization to Can s 3, a non-specific lipid protein (ns-LTP) from Cannabis sativa. Sensitization and elicitation of allergic symptoms seem to occur mainly through direct exposure. We report two patients in whom allergy could have resulted from passive exposure to cannabis. History was taken and skin prick tests with cannabis extracts rich in ns-LTP were performed. Total and specific IgE´s were quantified for industrial hemp and recombinant (r), or native (n) components: rCan s 3 (Cannabis sativa), rPru p 3 (Prunus persica), bromelain, rBet v 1 and rBet v 2 (Betula verrucosa), rPhl p 1 and rPhl p 5b (Phleum pratensis), nArt v 1 and nArt v 3 (Artemisia vulgaris). Finally, basophil activation tests were performed with rCan s 3. Both patients, denying any previous active exposure to cannabis and presenting with respiratory and/or cutaneous allergic symptoms upon passive cannabis exposure, also reported severe allergic symptoms to plant-foods. All patients showed positive SPT results for cannabis, sIgE reactivity to rCan s 3 and basophil activation upon stimulation with rCan s 3. Although it is difficult to demonstrate with certainty, we believe that our case histories suggest that cannabis-related allergies might result from passive exposure.

Histamine and its release can be studied by multicolor flow cytometry on a single cell level by an enzyme affinity method (HistaFlow®). However, for the time-being, the clinical and scientific application of the HistaFlow® technique remains limited. This study aims at verifying the reliability of the HistaFlow® as an instrument to quantify IgE-mediated basophil responses to drugs, i.e. rocuronium, which are believed to be less potent basophil activators than large proteinaceous allergens. Ten patients and three exposed control individuals were included in this study. Each subject underwent in vitro basophil activation tests (HistaFlow®) with 0.16 and 1.6 mmol/L rocuronium. Patients showed an activation of basophils ranging from 11 to 86% of CD63 positive basophils and a median histamine release per cell from 68 to 100% after stimulation with an optimal concentration of 1.6 mmol/L rocuronium. For the control individuals no activation was demonstrable. This study confirms that the HistaFlow® technique is a reliable tool to study histamine release by individual cells in response to drugs. Although the HistaFlow® technique will probably not add to the diagnostic management of rocuronium allergy, our findings suggest that the technique could constitute an important asset for future studies on the pathomechanism(s) of immediate drug hypersensitivity reactions.

Oralemijtenanafylaxie (OMA), ook het pancake syndrome genoemd, is een aandoening die gekenmerkt wordt door (ernstige) allergische reacties ten gevolge van de inname van voedsel waarin bloem zit gecontamineerd met mijten. De kliniek van OMA is zeer verscheiden en wordt bepaald door de plaats en de mate van mastcellen/basofielendegranulatie en treedt doorgaans op binnen het uur na de ingestie. De meest voorkomende symptomen zijn kortademigheid, angio-oedeem, wheezing en neusloop. Vooralsnog blijven de allergenen verantwoordelijk voor OMA niet geïdentificeerd. De diagnose van OMA berust op een suggestieve anamnese verenigbaar met een allergische reactie naar aanleiding van de inname van voedsel dat meel bevat, aangevuld met het aantonen van een sensibilisatie ten opzichte van mijten, het aantonen van mijten in de verdachte bloem, positieve huidtesten met de verdachte bloem en negatieve huidtesten met niet-gecontamineerde bloem. Niet zelden, zoals bij de in deze tekst besproken patiënten, is de gecontamineerde bloem niet meer beschikbaar, waardoor de correcte diagnose bemoeilijkt wordt. In dit manuscript wordt er voor het eerst simultane OMA beschreven bij een vader en zijn dochter, waarschijnlijk toe te schrijven aan beignetbloem gecontamineerd met mijten. Een literatuuroverzicht leert dat de diagnose van OMA gemakkelijk gemist wordt en overwogen moet worden in geval van anafylaxie sine causa apparente.

Immediate drug hypersensitivity reactions (DHR) constitute an important health condition, with serious consequences of inadequate diagnosis. In this article, some of the most important issues related to in vitro diagnosis of IgE-mediated allergies are discussed. In vitro diagnostics will benefit from expanded and novel insights and understandings in drug chemical reactivity, protein binding, biotransformation, degradation, identification of (cross-reactive) drug antigenic determinants, and deeper understanding of sensitization routes. Collective efforts should be undertaken to activate fundamental and clinical investigations.

Introduction Anaesthesia-related allergy is a rare but potentially life-threatening condition with serious consequences of diagnostic error. The authors report their experience of a 10-year survey in a Flemish referral centre. Methods Between January 2001 and December 2011, a total of 344 patients who experienced perioperative anaphylaxis were referred to our allergy centre. Allergy was documented on the basis of clinical history, skin tests, measurement of specific immunoglobulin E (sIgE) antibodies and/or basophil activation tests. Results A total of 344 patients were studied (111 male, 233 female; age ranging from 21 months to 86 years (median 47 years)). Mild reactions, mostly cutaneous, were reported in 110 patients and severe potentially life-threatening reactions in 176 patients. In the remainder 58 patients severity of the reaction was not reported. An IgE-mediated pathomechanism was documented in 246 cases (72%). Importantly, an IgE-mediated mechanism was not restricted to the severe reactions but also observed in 57% of the mild reactions. The most common offenders were neuromuscular blocking agents (NMBA) (40%), latex (25%), β-lactam antibiotics (12%) and chlorhexidine (9%). In 18 patients (7%) with an IgE-mediated allergy more than 1 causative agent was identified. In 7 patients, an indolent mastocytosis was diagnosed. Conclusion In our region, the most frequent causes of anaphylaxis during general anaesthesia are NMBA, particularly rocuronium, latex, antibiotics and chlorhexidine. Given the prevalence of double sensitization it is advocated to test all potential causative agents. Indolent mastocytosis should not be overlooked. Confirmatory testing should not be restricted to patients with severe anaesthesia-related anaphylaxis but also offered to patients with mild (cutaneous) reactions.

De ziektegeschiedenis van een patiënte met een aardbeienallergie wordt beschreven. Na een grondige anamnese aangevuld met in-vitro- en in-vivodiagnostiek wordt er achterhaald dat de aardbeienallergie geen alleenstaand fenomeen is, maar dat de patiënte ondertussen verschillende gevoeligheden voor fruit en groenten vertoont die hoogstwaarschijnlijk berusten op een kruisallergie voor Cannabis sativa. Zoals in dit tijdschrift reeds werd beschreven, lijkt deze kruisallergie tussen cannabis en fruit/groenten geassocieerd met een gevoeligheid voor een non-specific lipid transfer protein (ns-LTP). De identificatie van deze kruisallergie werd daarbij verricht aan de hand van componentgeoriënteerde diagnostiek. Het strikt vermijden van enig gebruik van en passieve blootstelling aan cannabis werd aangeraden, evenals het vermijden van vruchten en groenten die ondertussen verantwoordelijk gebleken zijn voor min of meer ernstige allergische reacties.

Allergieën voor genotsmiddelen zoals drugs en alcohol worden zelden gemeld. Vermoedelijk betreft het een onderrapportering mede door het illegale karakter van sommige ervan. Toch is er een toenemend aantal meldingen betreffende allergieën voor cannabis, opioïden, cocaïne, kava, amfetaminen, ketamine, efedra, khat en nootmuskaat.

The example reported here illustrates the frequent belief that innocent products such as central venous catheters do not produce allergic reactions. However, they might be impregnated with chlorhexidine and elicit serious life-threatening anaphylaxis in patients with allergy to this antiseptic agent.

Basophils are key effector cells in allergic inflammatory reactions. However, the mechanisms of FcεRI-induced degranulation are complex and remain to be disentangled. Signal transducer and activator of transcription (STAT) molecules modulate various cell functions. STAT5 appears to be essential for IgE-mediated mast cell function, but its role in human basophils after cross-linking FcεRI is unknown. In this study, STAT5 phosphorylation was investigated by flow cytometry, and combined with analyses of the degranulation marker CD63 at single cell level. Kinetics of STAT5 phosphorylation were studied in basophils of birch pollen allergic patients and showed a fast phosphorylation induced by interleukin (IL)-3, but not with antigen alone. Stimulating basophils with a mixture of allergen and IL-3 resulted in a two to three fold higher phosphorylation of STAT5 than induced by IL-3 alone. In the presence of IL-3, antigen elicited a dose-dependent STAT5 response. In conclusion, this study demonstrates that STAT5 in human basophils is activated through both the IL-3 and the FcεRI signaling pathway.

Background: Allergy to rocuronium can be life-threatening. Correct diagnosis is a prerequisite because of serious consequences of diagnostic error. Objective: To assess skin testing, quantification of specific IgE (sIgE) and flowassisted activation of basophils [basophil activation test (BAT)] in the diagnosis of rocuronium allergy. Methods: This study comprises 104 curarized patients with a history of profound hypotension and severe bronchospasm immediately after induction of anaesthesia. All patients had skin tests, quantification of sIgE and BAT to rocuronium, together with investigations for all relevant compounds administered during anaesthesia that could have evoked the reaction. Diagnosis of rocuronium allergy was considered definite when the patient demonstrated a positive outcome for at least two of the three aforementioned tests. Results: The positive predictive value for skin testing, BAT and sIgE was 98% (CI 95%: 9299%), 97% (CI 95%: 88100%) and 83% (CI 95%: 7489%), respectively. The negative predictive value for skin testing, BAT and sIgE was 96% (CI 95%: 8699%), 75% (CI 95%: 6775%) and 72% (CI 95%: 5883%), respectively. Cross-reactivity with vecuronium was documented in 69% of the patients. Conclusion: Skin testing merits the status of primary diagnostic investigation to document rocuronium allergy and cannot be substituted by quantification of sIgE or BAT. SIgE can offer a diagnostic advantage in cases where skin tests yield negative results. However, additional tests (e.g. BAT) are of capital importance in patients with negative skin tests and positive sIgE results to help in interpreting the clinical significance of a positive sIgE result.

Introduction: The impact of processing on the allergenicity of peanut (Arachis hypogaea) proteins has traditionally been studied using immunoglobulin (Ig) E binding assay. However, as this technique does not assess the potential of an allergen to trigger basophils and mast cells, studies based on it can hardly be considered complete. We evaluated the effect of processing on peanut allergenicity using fl ow-cytometric quantifi cation of in vitro basophil activation (basophil activation test [BAT]). Patients and Methods: Basophils from 10 patients with severe peanut allergy and 3 peanut-tolerant individuals were stimulated with extracts from 5 raw and thermally processed peanut varieties. Data were compared using protein staining (sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]) and IgE immunoblotting. Results: Stimulation with different extracts resulted in patient-dependent and variety-dependent effects on basophil activation. SDS-PAGE revealed a considerable loss of identifi able bands, especially for the South Africa Common Natal, Argentina Runner, and US Virginia varieties. The results of IgE immunoblotting in patients were similar, irrespective of the responses observed in the BAT. Conclusions: The impact of thermal processing on the capacity of peanuts to trigger basophils seems highly divergent between patients and cannot be predicted using SDS-PAGE or IgE binding. BAT can be considered a complementary tool for the evaluation of food allergenicity.

Hereditary angioedema (HAE) is an inherited disorder characterized by recurrent, circumscribed, nonpitting, non-pruritic, and rather painful subepithelial swelling of sudden onset, which fades during the course of 4872 hours, but can persist for up to 1 week. Lesions can be solitary or multiple, and primarily involve the extremities, larynx, face, esophagus, and bowel wall. Patients withHAEexperience angioedema because of a defective control of the plasma kinin-forming cascade that is activated through contact with negatively charged endothelial macromolecules leading to binding and auto-activation of coagulation factor XII, activation of prekallikrein to kallikrein by factor XIIa, and cleavage of high-molecular-weight kininogen by kallikrein to release the highly potent vasodilator bradykinin. Three forms of HAE have currently been described. Type I and type II HAE are rare autosomal dominant diseases due to mutations in the C1-inhibitor gene (SERPING1). C1-inhibitor mutations that cause type I HAE occur throughout the gene and result in truncated or misfolded proteins with a deficiency in the levels of antigenic and functional C1-inhibitor. Mutations that cause type II HAE generally involve exon 8 at or adjacent to the active site, resulting in an antigenically intact but dysfunctional mutant protein. In contrast, type III HAE (also called estrogen-dependent HAE) is characterized by normal C1-inhibitor activity. The diagnosis of HAE is suggested by a positive family history, the absence of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colic, and episodes of laryngeal edema. Estrogens may exacerbate attacks, and in some patients attacks are precipitated by trauma, inflammation, or psychological stress. For type I and type II HAE, diminished C4 concentrations are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-inhibitor antigen (type I) in most kindreds, but some kindreds have an antigenically intact but dysfunctional protein (type II) and require a functional assay to establish the diagnosis. There are no particular laboratory findings in type III HAE. Prophylactic administration of either 17a-alkylated androgens or synthetic antifibrinolytic agents has proven useful in reducing the frequency or severity of attacks. Plasma-derived C1-inhibitor concentrate, recombinant C1-inhibitor, ecallantide (DX88; a plasma kallikrein inhibitor) and icatibant (a bradykinin B2 receptor antagonist) have demonstrated significant efficacy in the treatment of acute attacks, whereas the C1-inhibitor concentrate has also provided a significant benefit as long-term prophylaxis. However, these drugs are not licensed in all countries and are not always readily available.

Background Little data are available on the relationship between indirect antibiotic exposure of the child in utero or during lactation and allergic diseases. On the other hand, several studies have been conducted on the association with direct post-natal antibiotic exposure, but the results are conflicting. Objective The aim of this study was to investigate pre- and post-natal antibiotic exposure and the subsequent development of eczema, recurrent wheeze and atopic sensitization in children up to the age of 4 years. MethodsWe conducted an aetiologic study in 773 children based on a prospective birth cohort project in which environmental and health information were collected using questionnaires. Antibiotic exposure was assessed as maternal antibiotic intake during pregnancy and during lactation and as medication intake of the child. The chronology of exposures and outcomes was taken into account during the data processing. At the age of 1 and 4 years, a blood sample was taken for the quantification of specific IgE. Results Prenatal antibiotic exposure was significantly positively associated with eczema, whereas no association was found with recurrent wheeze and atopic sensitization.We found a positive, although statistically not significant, association between antibiotic exposure through breastfeeding and recurrent wheeze. Neither eczema nor atopic sensitization was significantly associated with antibiotic exposure through breastfeeding. Finally, we observed a negative association between the use of antibiotics in the first year of life and eczema and atopic sensitization, and also between antibiotic use after the first year of life and recurrent wheeze, eczema and atopic sensitization. Conclusion Indirect exposure to antibiotics (in utero and during lactation) increases the risk for allergic symptoms in children, while direct exposure to antibiotics appears to be protective. The biological mechanisms underlying these findings still need to be elucidated.

Diagnosis of IgE-mediated allergies is not always straightforward, as traditional tests can yield equivocal or negative results and provocation tests are hampered by several practical and ethical limitations. During the last decades two new in vitro techniques have entered the field of allergy diagnosis, that is, flow-assisted analysis of allergen-specific activated basophils and component-resolved diagnosis (CRD). This review focuses on component-resolved allergy diagnosis by microarray that has evolved from recent advances in molecular allergology and biochip technology. The technique allows a comprehensive analysis of individual sensitization profiles with multiplexed purified and recombinant allergens within a single run using only a minute amount of serum, providing information that largely exceeds the output from current sIgE capturing tools. Actually, multiplexing allows identification of diagnostic patterns that may facilitate the formulation of diagnostic algorithms. Although CRD by microarray sounds promising, the diagnostic performance requires further intensive assessment before it can enter mainstream application. In our opinion, the technique should currently be considered a complementary diagnostic tool rather than a first-line choice.

OBJECTIVES: TNF-α inhibition therapy affects the systemic immune response in rheumatoid arthritis by influencing T cell subtypes (Th1, Th2, Treg), but its effect on the intracellular signal transduction in T cells remains largely unexplored. Here we studied the activation of Th1-associated signalling molecule STAT4 and Th2-associated STAT6 in CD4+ T cells. METHODS: Eight rheumatoid arthritis patients were studied before and after 12 weeks of adalimumab therapy and compared to 8 healthy individuals. Peripheral blood mononuclear cells (PBMC) were analysed flow cytometrically either directly after isolation or after 24 hours of anti-CD3/anti-CD28 stimulation, to determine spontaneous and IL-4/IL-12-induced STAT4 and STAT6 phosphorylation in CD4+ T cells. Cytokine production by stimulated PBMC was measured in the supernatant using a cytometric bead array. Non-parametric statistical tests were applied. RESULTS: After adalimumab therapy, phospho-STAT6 increased, both in freshly isolated and anti-CD3/anti-CD28-stimulated CD4+ T cells. The STAT6 response to brief IL-4 stimulation did not change. In healthy individuals and adalimumab-treated patients, anti-CD3/anti-CD28 induced the phosphorylation of STAT4, but not in untreated patients. IFN-γ production in untreated patients was significantly lower than in healthy individuals or adalimumab-treated patients. In contrast, the production of IL-4, IL-6 and IL-12 was not influenced. CONCLUSIONS: Adalimumab therapy increases Th2-associated STAT6 phosphorylation and restores the activation-induced STAT4 phosphorylation to the levels in healthy individuals. This advocates against a pro-inflammatory effect of Th1-associated STAT4 and might provide an explanation for the influence of TNF inhibition therapy on the systemic T cell response in rheumatoid arthritis.

Background: Symptoms of hazelnut allergy seem related to geographic and possibly agevariations in allergen recognition. Objective: To investigate sensitization profiles of hazelnut allergy in different age-groups in a birch-endemic region using component resolved diagnosis by microarray. Methods: Sixty-five hazelnut allergic patients, 27 healthy control individuals tolerant to hazelnut and 34 birch pollen allergic but hazelnut tolerant individuals were included. All blood samples were analysed using ISAC microarray. Results: Twenty-nine hazelnut allergic patients suffered from a systemic reaction (17 preschool children with a median age of 2 years, 6 school children and 6 adults) whereas 36 patients reported an oral allergy syndrome (OAS; 3 preschool- and 9 school children and 24 adults). In the hazelnut allergic preschool children with systemic reactions, 65% were sensitized to Cor a 9, 12% to Cor a 8, 18% to Cor a 1.04, 6% to Cor a 1.0101 and 29% to Bet v 1. Of the school aged systemic reactors, 50% were sensitized to Cor a 9, 17% to Cor a 8, 50% to Cor a 1.04 and Cor a 1.0101 and 67% to Bet v 1. In adults with hazelnut allergy, 3.3% was sensitized to Cor a 9, 6.7% to Cor a 8, 90% to Cor a 1.04 and Bet v 1 and 87% to Cor a 1.0101. In regard to systemic reactors in this group, 17% was sensitized to Cor a 9, 33% to Cor a 8 and Cor a 1.0101 and 50% to Cor a 1.04 and Bet v 1. In the OAS patients, irrespective the age group, all were sensitized to Bet v 1 and over 97% to Cor a 1.04 and Cor a 1.0101. No Page 2 of 32 Scholarone, Inc. Support (434) 964 4100 Pediatric Allergy and Immunology For Peer Review sensitization to Cor a 9 or Cor a 8 was found in patients with only an OAS. Of the birch pollen allergic patients, tolerant to hazelnut, none were sensitized to Cor a 9 or Cor a 8, 56% to Cor a 1.0101, 82% were sensitized to Cor a 1.04 and 92% to Bet v 1. In healthy controls, no sensitization to components of hazelnut, hazel- or birch pollen was demonstrable. Conclusion: Hazelnut allergy in a birch-endemic region exhibits age-related sensitization profiles with distinct clinical outcomes that can be identified using component resolved diagnosis. The majority of hazelnut allergic preschool- and school children in a birch-endemic region show systemic reactions on consumption of processed hazelnut, mostly being sensitized to the hazelnut legumin-like allergen Cor a 9 but unrelated to birch pollen allergy. In contrast, adults generally suffer from an OAS apparently as a result of cross-reactivity between Cor a 1.04 from hazelnut and Bet v 1 from birch pollen.

De correcte identificatie van het (de) verantwoordelijke allerge(e)n(en) en mogelijk kruisreactieve structuren is een absolute voorwaarde voor het instellen van de juiste saneringsmaatregelen en het opstarten van behandelingen zoals allergeenspecifieke immunotherapie (hyposensibilisatie). Een gerichte grondige anamnese en klinisch onderzoek zijn hierbij van vitaal belang en moeten leiden tot een klinisch vermoeden dat aan de hand van betrouwbare in-vitro- en/of in-vivoallergietesten dient te worden geobjectiveerd. Dit artikel heeft tot doel de beschikbare in-vitro- en in-vivoallergietesten te schetsen en spitst zich daarbij vooral toe op de mogelijkheden en beperkingen van de verschillende technieken. Tevens worden enkele nieuwe ontwikkelingen toegelicht. Hieruit mag blijken dat er enkele beloftevolle doorbraken zijn, maar dat een behoorlijke kennis van de belangrijkste allergenen en hun onderlinge kruisreactiviteit onontbeerlijk wordt voor een correcte interpretatie van de bekomen resultaten. Tot slot wordt gewaarschuwd voor enkele onorthodoxe diagnosemethoden.

Secundaire voedselallergieën ontstaan doorgaans als gevolg van een voorafgaande allergie voor pollen of natuurrubberlatex. Kruisreactiviteit is daarbij het onderliggende mechanisme. Allergenen aanwezig in pollen en natuurlijke latex kunnen de productie van IgE-antistoffen uitlokken die kunnen reageren met structuurhomologen aanwezig in groenten en fruit. De diagnose van een secundaire voedselallergie wordt vooral bemoeilijkt door de lage specificiteit van de traditionele IgE-testen die geen onderscheid maken tussen sensibilisate en echte allergie. Nieuwe technologieën zoals asofielenactivatietesten en gezuiverde evenals recombinante allergenen vormen ongetwijfeld een diagnostische aanwinst.