[The improvement of the transfer into daily life of progressive relaxation after an inpatient psychosomatic rehabilitation]. / Verbesserung des Transfers von Progressiver Relaxation in den Alltag der Patienten nach stationärer psychosomatischer Rehabilitation.

AIM OF THE STUDY: The aim of the current study was the identification of predictors for a successful transfer of progressive relaxation (PR) into clinical and daily life. Furthermore the development of tension-related symptoms dependening of the frequency of continuous practise was detected. METHODS: 411 patients of a psychosomatic rehabilitation clinic attended a 6-h-course of progressive relaxation and were interviewed at 3 different times by a modified version of the "diagnostisches und evaluatives Instrumentarium für Entspannungstraining und Entspannungstherapie (ET-EVA)": at the beginning of therapy (T1), at discharge (T2) and 3 months after discharge by postal service (T3). After 3 months 274 patients (78.3%) sent the completed questionnaires back. The frequency of exercising by at least once a week was defined as successful. To detect the extent of symptom improvement, difference values between the different measuring times and effect sizes were calculated. To identify predictors of the frequency of daily practise, bivariate correlations and linear regression were used. RESULTS: 69.4% of the patients continued the exercises successfully beyond the course. The improved experience of relaxation directly after the program (r=-0.184; p<0.01) had a positive influence on the frequency of practising during hospital stay. 3 months after discharge 50.4% of the participants were practising at least once a week. The frequency of practise during hospital stay (r=0.558; p<0.01) and the experience of relaxation at T3 (r=-0.356; p<0.01) could be identified as predictors of a successful transfer into daily life of progressive relaxation. In the context of the linear regression the effect of the frequency of practise during hospital stay (Beta=0.506; p<0.01) and the experience of relaxation after 3 months (Beta=-0.275; p<0.01) remained significant predictors and explaines 40.9% of the variance. The items of all 6 symptom scales decreased significantly from T1 to T2 (p<0.01) and the feeling of discomfort after 3 months was significantly below the base level of T1 (p<0.01). The patients who practised at least once a week - compared to the not-practising patients - declared significantly less tension-related symptoms at T3 (p<0.01) and could achieve a significantly stronger change of wellbeing and relaxation experience at T2 and T3 (p<0.01). CONCLUSION: 50.4% of the patient implemented the relaxation training in their daily routine. The experienced alteration in terms of self-efficacy plays a meaningful role concerning the frequency of practise in hospital stay and daily routine. In future courses attention should be paid to the initial experience of relaxation. The frequency of practise once a week turned out to be the most effective.

Molecular characterization of a human immunoglobulin G4 antibody specific for the major birch pollen allergen, Bet v 1.

BACKGROUND: Allergen-specific IgG4 antibodies induced by specific immunotherapy are thought to represent a protective immune response. Objective Our aim was the molecular characterization of a human IgG4 antibody (BAB5) specific for the major birch pollen allergen Bet v 1 that was derived from an immunotherapy-treated patient. METHODS: The cDNA coding for BAB5 was obtained by reverse transcriptase-PCR from the BAB5-producing cell line, compared with the germ line sequences and was expressed as a soluble antibody fragment in Escherichia coli. The epitope specificity and cross-reactivity of BAB5 were investigated with recombinant and synthetic Bet v 1 fragments and Bet v 1 homologous allergens from pollen. The ability of BAB5 to block allergic patients IgE was determined by competition experiments and sandwich ELISA. RESULTS: BAB5 is an affinity-matured Bet v 1-specific IgG4 antibody that reacts exclusively with Bet v 1 but not with Bet v 1-related allergens. Unlike an earlier-described monoclonal IgG1-blocking antibody, BAB1, which had been isolated from the same patient, BAB5 did not block allergic patients' IgE reactivity to Bet v 1. CONCLUSION: Our study demonstrates that not all allergen-specific IgG antibodies inhibit IgE recognition of allergens and can contribute to the success of immunotherapy. The epitope specificity and affinity of IgG antibodies but not their isotype are decisive for their protective activity.

Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination.

BACKGROUND: Almost 100 million allergic patients are sensitized to the major birch pollen allergen, Bet v 1, a 17 kDa protein containing most of the IgE epitopes present in pollens of trees belonging to the Fagales order and plant-derived food. OBJECTIVE: Our aim was to develop an approach for the rational design of B cell epitope-derived, non-allergenic peptide allergy vaccines. METHODS: According to the three-dimensional (3-D) structure of birch pollen allergen, Bet v 1, six peptides comprising 25-32 preferably solvent-exposed amino acids were synthesized. RESULTS: Because of lack of secondary structure, the peptides showed no allergenic activity in allergic patients. In a mouse model of birch pollen allergy, peptide vaccination induced Bet v 1-specific IgG and prevented IgE-mediated allergic sensitization to Bet v 1. The protective role of peptide-induced blocking antibodies is demonstrated by inhibition of allergic patients IgE binding to the allergen and by blocking of allergen-induced basophil degranulation. CONCLUSION: Our results indicate the mechanistic importance of blocking antibodies for allergy vaccination and present a B cell epitope-based approach for the rational design of safe peptide allergy vaccines whenever the structure of the disease-eliciting allergen is known.

Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies.

BACKGROUND: Allergen-specific immunotherapy represents a causal form of treatment for IgE-mediated allergies. The allergen extract-based analyses of immunotherapy-induced effects yielded highly controversial results regarding a beneficial role of therapy-induced IgG antibodies. OBJECTIVE: We analysed allergen-specific IgE, IgG subclass, and IgM responses in patients treated with a grass pollen allergy vaccine adjuvanted with monophosphoryl lipid A (MPL), a Th1-inducing agent, and in a placebo group using recombinant timothy grass pollen allergen molecules (rPhl p 1, rPhl p 2, rPhl p 5). RESULTS: The strong induction of allergen-specific IgG1 and IgG4 antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy-induced allergen-specific IgM and IgG2 responses were also noted in several actively treated patients. An inhibition of allergen-dependent basophil histamine release was only obtained with sera containing therapy-induced allergen-specific IgG, but not with sera obtained before therapy or from placebo-treated patients. Moreover, patients with therapy-induced allergen-specific IgG antibodies showed a reduced induction of allergen-specific IgE responses during seasonal grass pollen exposure. CONCLUSION: Successful immunotherapy with the MPL-adjuvanted grass pollen allergy vaccine is associated with the production of allergen-specific IgG antibodies. These blocking antibodies may have protective effects by inhibiting immediate-type reactions and systemic increases of IgE responses caused by seasonal allergen exposure.

Analysis of the sensitization profile towards allergens in central Africa.

BACKGROUND: Almost no information is available regarding the prevalence of IgE-mediated allergies and the disease-eliciting allergens in tropical Africa. OBJECTIVE: To study IgE-mediated allergies and the allergen profile in allergic patients from Zimbabwe. METHODS: The frequency of sensitization to common environmental allergen sources was determined by skin prick testing in 650 allergic patients from Zimbabwe. Fifty representative sera were analysed for IgE reactivity to 20 respiratory and 20 food allergen extracts by multiallergen extract testing. The IgE reactivity profiles to recombinant pollen and mite allergens were compared between grass pollen- and mite-sensitized patients from Zimbabwe and central Europe. Sera from grass pollen-allergic patients were also analysed for IgE reactivity to nitrocellulose-blotted natural timothy grass and Bermuda grass pollen allergens. RESULTS: IgE-mediated allergies were found to be common in Zimbabwe. Similar to the situation in central Europe, mites and grass pollens represented the most prevalent allergen sources. However, the IgE reactivity profiles determined with single recombinant pollen and mite allergens revealed interesting differences between the European and African patients, which most likely reflect the local allergen exposure. CONCLUSIONS: The striking differences regarding sensitization to grass pollen and mite allergens between African and European patients revealed by recombinant allergen-based testing emphasize the need for component-resolved allergy testing to optimize allergy prevention and therapy in different populations.

Mucosal tolerance as therapy of type I allergy: intranasal application of recombinant Bet v 1, the major birch pollen allergen, leads to the suppression of allergic immune responses and airway inflammation in sensitized mice.

BACKGROUND: Several studies have demonstrated that mucosal administration of soluble antigens can prevent the onset or reduce the severity of certain autoimmune diseases or allergies. Few studies exist showing the efficacy of mucosal tolerance for therapy of such diseases. OBJECTIVE: The aim of the present study was to modulate an allergic immune response by intranasal antigen administration in an already sensitized organism. METHODS: A murine model of allergic asthma to birch pollen (BP) and its major allergen Bet v 1 was utilized. Sensitized mice were intranasally treated with recombinant (r)Bet v 1 in different concentrations and at different intervals. On the day the mice were killed, blood and bronchoalveolar lavage fluids were taken and immediate type I skin tests were performed. T cell proliferation and cytokine production (interleukin (IL)-5, interferon (IFN)-gamma) were measured in spleen and lung cell cultures. RESULTS: Mucosal treatment with rBet v 1 (3 x 50 microg in 4 day intervals) led to a reduction of type I skin reactions, suppressed immunoglobulin (Ig)G1/IgE antibody levels and markedly decreased IL-5 and IFN-gamma production in vitro in spleen and lung cell cultures. Moreover, lung inflammation (i.e. eosinophilia and IL-5 levels in bronchoalveolar lavage fluids) was significantly suppressed by the treatment. CONCLUSION: Our results demonstrate that intranasal treatment with rBet v 1 reduced systemic allergic immune responses as well as airway inflammation in BP-sensitized mice. We therefore suggest that mucosal tolerance induction with recombinant allergens could be a promising concept for the therapy of allergic diseases.

Intranasal treatment with a recombinant hypoallergenic derivative of the major birch pollen allergen Bet v 1 prevents allergic sensitization and airway inflammation in mice.

BACKGROUND: The major birch pollen allergen Bet v 1 represents one of the most prevalent environmental allergens responsible for allergic airway inflammation. OBJECTIVE: In the present study we sought to compare the complete recombinant Bet v 1 allergen molecule with genetically produced hypoallergenic fragments of Bet v 1 regarding mucosal tolerance induction in a mouse model of allergic asthma. METHODS: BALB/c mice were intranasally treated with recombinant Bet v 1 or with two recombinant Bet v 1 fragments (F I: aa 1-74; F II: aa 75-160) prior to aerosol sensitization with birch pollen and Bet v 1. RESULTS: Intranasal application of F II, containing the major T cell epitope, led to significant reduction of IgE/IgG1 antibody responses, in vitro cytokine production (IL-5, IFN-gamma, IL-10) and negative immediate cutaneous hypersensitivity reactions comparable to the pretreatment with the complete rBet v 1 allergen. Moreover, airway inflammation (eosinophilia, IL-5) was inhibited by the pretreatment with either the complete Bet v 1 or F II. However, for prevention of airway hyperresponsiveness the complete molecule was required. The mechanisms leading to immunosuppression seemed to differ in their dependence on the conformation of the molecules, since tolerance induced with the complete Bet v 1, but not with F II, was transferable with spleen cells and associated with increased TGF-beta mRNA levels. CONCLUSION: We conclude that mucosal tolerance induction with recombinant allergens and genetically engineered hypoallergenic derivatives thereof could provide a convenient and safe intervention strategy against type I allergy.

Evaluation of the allergenic potential of Ginkgo biloba extracts.

Ginkgo biloba extracts are used for the treatment of central and peripheral malperfusion, cerebral insufficiency and dementia. Between 1996 and 1998, several patients in Austria who had received parenteral Ginkgo extracts were reported to have developed allergy-like symptoms. The aim of the present study was to determine whether Ginkgo biloba extracts contain type I allergens. The protein content of Ginkgo biloba extracts was determined by BCA protein determination and SDS-PAGE. We used sera from 95 polysensitized plant-allergic patients (the sera contained IgE antibodies against most plant allergens), and rabbit antisera raised against defined recombinant plant allergens. The presence of allergens in Ginkgo extracts was determined by dot-blotting and Wester blot. Neither rabbit antisera nor IgE antibodies of patients reacted to the Ginkgo extracts. In addition, it was shown that prick testing of the skin could be conveniently used to study Gingko extracts for allergenic activity. In conclusion, no evidence for the presence of type I allergens in Ginkgo extracts was found. We recommend serological and/or skin testing to exclude sensitisation to components of Ginkgo biloba extracts.

Nonanaphylactic synthetic peptides derived from B cell epitopes of the major grass pollen allergen, Phl p 1, for allergy vaccination.

Worldwide more than 200 million individuals are allergic to group 1 grass pollen allergens. We have used the major timothy grass pollen allergen Phl p 1, which cross-reacts with most grass-, corn-, and monocot-derived group 1 allergens to develop a generally applicable strategy for the production of hypoallergenic allergy vaccines. On the basis of the experimentally determined B cell epitopes of Phl p 1, we have synthesized five synthetic peptides. These peptides are derived from the major Phl p 1 IgE epitopes and were between 28-32 amino acids long. We demonstrate by nuclear magnetic resonance that the peptides exhibit no secondary and tertiary structure and accordingly failed to bind IgE antibodies from grass pollen allergic patients. The five peptides, as well as an equimolar mixture thereof, lacked allergenic activity as demonstrated by basophil histamine release and skin test experiments in grass pollen allergic patients. When used as immunogens in mice and rabbits, the peptides induced protective IgG antibodies, which recognized the complete Phl p 1 wild-type allergen and group 1 allergens from other grass species. Moreover, peptide-induced antibodies inhibited the binding of grass pollen allergic patients IgE antibodies to the wild-type allergen. We thus demonstrate that synthetic hypoallergenic peptides derived from B cell epitopes of major allergens represent safe vaccine candidates for the treatment of IgE- mediated allergies.

Mucosal tolerance induction with hypoallergenic molecules in a murine model of allergic asthma.

Type I allergy, frequently elicited by airborne allergens, has constantly increased within recent years. Birch pollen and its major allergen Bet v 1 represent a major source of type I allergens. By genetic engineering hypoallergenic Bet v 1 fragments were produced, which lost the IgE binding capacity but retained the T cell epitopes. We have established a murine model of aerosol sensitization to birch pollen and its major allergen Bet v 1, leading to type I allergic immune responses and airway hyperresponsiveness. In the present study we demonstrate that mucosal administration of recombinant Bet v 1 prior to sensitization led to allergen-specific suppression of B and T cell responses in vivo and in vitro, reduction of eosinophilic infiltration in the lungs and inhibition of airway hyperresponsiveness. Intranasal pretreatment with the nonanaphylactic fragments of Bet v 1 prevented allergic immune responses and airway inflammation to the same degree as the pretreatment with the complete molecule. We conclude from our studies that mucosal tolerance induction with hypoallergenic molecules could provide a safe and convenient treatment strategy against type I allergies.

Recombinant allergen molecules: tools to study effector cell activation.

The IgE antibody-mediated activation of allergic effector cells is the key pathomechanism underlying the immediate symptoms of Type I allergy, a genetically determined hypersensitivity disease affecting 25% of the population. In recent years important environmental allergens and their epitopes have become available as structurally defined recombinant molecules. In addition, corresponding human monoclonal IgE and IgG antibodies have been isolated. This review summarizes data obtained regarding the three-dimensional structure of allergens, their IgE epitopes and the recognition of allergens by IgE and IgG antibodies. In particular, we discuss results of recent in vitro and in vivo studies with defined allergen molecules, their epitopes and the corresponding antibodies which support the hypothesis that the density and geometrical arrangement of IgE epitopes on a particular allergen molecule may profoundly affect effector cell activation. If the structural requirements for effector cell activation can be delineated, it may be envisaged that, based on this knowledge, allergens can be converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such allergen derivatives may be used for allergen-specific immunotherapy with reduced risk of inducing anaphylactic side effects.

T cell epitope-containing hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1, induce blocking antibodies.

Allergen-specific immunotherapy represents one of the few curative approaches toward type I allergy. Up to 25% of allergic patients are sensitized against the major birch pollen allergen, Bet v 1. By genetic engineering we produced two recombinant (r) Bet v 1 fragments comprising aa 1-74 and aa 75-160 of Bet v 1, which, due to a loss of their native-like fold, failed to bind IgE Abs and had reduced allergenic activity. Here we show that both fragments covering the full Bet v 1 sequence induced human lymphoproliferative responses similar to rBet v 1 wild type. The C-terminal rBet v 1 fragment induced higher lymphoproliferative responses than the N-terminal fragment and represented a Th1-stimulating segment with high IFN-gamma production, whereas the N-terminal fragment induced higher IL-4, IL-5, and IL-13 secretion. Immunization of mice and rabbits with rBet v 1 fragments induced IgG Abs, which cross-reacted with complete Bet v 1 and Bet v 1-related plant allergens and strongly inhibited the IgE binding of allergic patients to these allergens. Thus, our results demonstrate that hypoallergenic T cell epitope-containing rBet v 1 fragments, despite lacking IgE epitopes, can induce Abs in vivo that prevent the IgE binding of allergic patients to the wild-type allergen. The overall demonstration of the immunogenic features of the hypoallergenic rBet v 1 fragments will now enable clinical studies for safer and more efficient specific immunotherapy.

A human monoclonal IgE antibody defines a highly allergenic fragment of the major timothy grass pollen allergen, Phl p 5: molecular, immunological, and structural characterization of the epitope-containing domain.

Almost 90% of grass pollen-allergic patients are sensitized against group 5 grass pollen allergens. We isolated a monoclonal human IgE Fab out of a combinatorial library prepared from lymphocytes of a grass pollen-allergic patient and studied its interaction with group 5 allergens. The IgE Fab cross-reacted with group 5A isoallergens from several grass and corn species. By allergen gene fragmentation we mapped the binding site of the IgE Fab to a 11.2-kDa N-terminal fragment of the major timothy grass pollen allergen Phl p 5A. The IgE Fab-defined Phl p 5A fragment was expressed in Escherichia coli and purified to homogeneity. Circular dichroism analysis revealed that the rPhl p 5A domain, as well as complete rPhl p 5A, assumed a folded conformation consisting predominantly of an alpha helical secondary structure, and exhibited a remarkable refolding capacity. It reacted with serum IgE from 76% of grass pollen-allergic patients and revealed an extremely high allergenic activity in basophil histamine release as well as skin test experiments. Thus, the rPhl p 5A domain represents an important allergen domain containing several IgE epitopes in a configuration optimal for efficient effector cell activation. We suggest the rPhl p 5A fragment and the corresponding IgE Fab as paradigmatic tools to explore the structural requirements for highly efficient effector cell activation and, perhaps later, for the development of generally applicable allergen-specific therapy strategies.

Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with rBet v 1 wild-type by skin prick and intradermal testing: results obtained in a French population.

BACKGROUND: Bet v 1, the major allergen in birch pollen, is recognized by more than 90% of patients allergic to birch in northern and central Europe. Immunotherapy is commonly performed with birch pollen extracts. Recently, hypoallergenic derivatives of Bet v 1 (rBet v 1 fragments, rBet v 1 dimer and trimer) were constructed and purified. OBJECTIVE: Our aim was to compare the allergenic activity of wild-type rBet v 1 with recombinant Bet v 1 derivatives (rBet v 1 fragments, dimer and trimer) with potentially reduced anaphylactic activity by skin testing in a French population. METHODS: Among the 36 birch pollen allergic patients included in the study, 29 were tested by skin prick testing and 30 by intradermal injections with purified monosubstances: rBet v 1 fragments (F1: aa1-74 and F2: aa75-160), Bet v 1 dimer and trimer. Intradermal tests were performed by the end-point intradermal titration method. Eight of the intradermally-tested patients were previously hyposensitized. Tests were performed over a period of 6 months (before, during and after birch pollen season); Bet v 1-specific IgE and IgG4 subclass responses were measured by immunoblotting and ELISA. RESULTS: All patients showed lower reactivity with the modified rBet v 1 allergens, both in skin prick and intradermal tests. In 25 and 23 out of 29 patients the lowest concentration of fragment 1 and 2, respectively, resulting in a positive prick test was 100-fold higher than the lowest concentration of monomer resulting in a positive prick test. For dimer it was 100-fold or more in 25 out of 29 patients, and for trimer it was 100-fold or superior in 26 out of 29 patients. By intradermal testing, the end-point concentration was 160-fold higher for trimer than for monomer in 24 patients and 40-fold higher in five patients. For the two fragments the end-point concentration was 160-fold higher in 20 out of 22 patients. CONCLUSION: Genetically modified hypoallergenic derivatives of the major birch pollen allergen, Bet v 1 showed reduced capacity to induce immediate type skin reactions. They may represent candidate molecules for immunotherapy of birch pollen allergy with reduced risk of anaphylactic side-effects.

Mutual boosting effects of sensitization with timothy grass pollen and latex glove extract on IgE antibody responses in a mouse model.

Type I allergy to natural rubber latex can be an important health problem for latex-exposed individuals (e.g., health care workers, spina bifida children). Also beyond these risk groups, a high sensitization rate of varying and partly unknown clinical relevance has been reported. Atopy represents a risk factor for latex allergy and recent studies indicate that patients suffering from pollen allergies may have pollen allergen-specific IgE antibodies which cross-react with latex allergens. In order to investigate whether sensitization to pollen allergens can have priming effects on the production of IgE antibodies against latex in vivo, a mouse model was established. Groups of 10 BALB/C mice were immunized with Al(OH)3-adsorbed pollen extracts from timothy grass, ragweed, mugwort, or birch. For control purposes, one additional group received adjuvant only and another group was not immunized. Half of the mice of each group were subsequently immunized with Al(OH)3-adsorbed latex glove extract, the other half with adjuvant only. Pollen and latex-specific IgE- and IgG1-antibody responses were analyzed by enzyme-linked immunosorbent assay and statistically evaluated by analysis of variance. Antibody responses to cross-reactive antigens were investigated by immunoblotting. We found significantly increased IgE reactivities to latex after pollen sensitization and vice versa. Moreover, mice immunized with timothy grass pollen extract alone - without subsequent latex immunization - displayed IgE reactivity to latex. Cross-reactive antibodies were directed against pollen antigens of approximately 60 kDa molecular weight. Our results thus demonstrate a mutual boosting effect of pollen and latex sensitization in vivo which may be also operative in polysensitized plant allergic patients.

Dissociation of allergen-specific IgE and IgA responses in sera and tears of pollen-allergic patients: a study performed with purified recombinant pollen allergens.

BACKGROUND: Trees and grass pollen allergens represent potent elicitors of allergic rhinoconjunctivitis and asthma. Little is known regarding the presence of allergen-specific IgA antibodies in sera and tears and their association with IgE responses in patients with allergic conjunctivitis. OBJECTIVE: The purpose of this study was to compare the specificities of IgE and IgA antibodies in sera and tears of pollen-allergic patients with conjunctivitis by using purified recombinant pollen allergens. METHODS: Sera and tears collected from 23 pollen-allergic and from 23 nonatopic individuals were analyzed for IgE and IgA reactivity to nitrocellulose-blotted birch and timothy grass pollen extracts. In addition, we determined the specificities of IgE, IgG(1-4), and IgA antibodies with use of a panel of purified recombinant pollen allergens (timothy grass: rPhl p 1, rPhl p 2, rPhl p 5; birch: rBet v 1, rBet v 2) in serum and tear samples by immunoblotting and ELISA. Statistical analyses of data were performed by t test and Mann Whitney U test. RESULTS: Serum and tears of many of the pollen-allergic individuals with conjunctivitis exhibited specificity for the very same pollen allergens. No allergen-specific IgE antibodies were detected in tears of nonatopic individuals. IgA antibodies in sera and tears of patients with allergic conjunctivitis were mainly directed against nonallergenic moieties and showed specificities that were significantly different from those of IgE antibodies. CONCLUSION: The dissociation of IgE and IgA responses and the lack of allergen-specific IgA antibodies in mucosal secretions (eg, tears) may contribute to allergic manifestations in target organs of atopy. Induction of allergen-specific IgA antibodies may hence be considered as a promising strategy for the treatment of mucosal forms of atopy.

Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy.

BACKGROUND: Type I allergic symptoms in the oropharyngeal mucosa upon contact with plant-derived food in patients with pollen allergies have been termed oral allergy syndrome (OAS). IgE cross-reactivity between pollen and food allergens represents the molecular basis for this phenomenon. The sensitizing allergen source (pollen or plant food) in OAS is a controversial issue. OBJECTIVE: We sought to determine the primary sensitizing molecules in patients with OAS. METHODS: We used recombinant birch pollen (rBet v 1 and rBet v 2) and plant food allergens (apple, rMal d 1; celery, rApi g 1; and carrot, rDau c 1), as well as natural pollen (birch and timothy grass) and plant food (apple, peach, kiwi, hazelnut, celery, and carrot) allergens, to identify cross-reactive allergens by using qualitative immunoblot inhibitions. In addition, we determined the percentage of plant food-specific IgE that can be preadsorbed with recombinant and natural pollen allergens by quantitative RAST inhibitions by using sera from 71 patients with OAS. RESULTS: Preincubation of sera with recombinant and natural pollen allergens led to an almost complete inhibition of IgE binding to plant food allergens in Western blots, as well as in RAST inhibition experiments. In contrast, recombinant plant food allergens poorly inhibited IgE binding to Bet v 1. CONCLUSION: Most IgE epitopes in plant food recognized by patients with OAS are resembled by pollen allergens. Thus pollen allergens may be responsible for the elicitation and maintenance of OAS.