Simplified AIT for allergy to several tree pollens-Arguments from the immune outcome analyses following treatment with SQ tree SLIT-tablet.

BACKGROUND: The SQ tree SLIT-tablet (containing birch extract) proved clinically significant effects during the pollen season for birch as well as alder/hazel. Immune outcomes of this treatment for allergens from multiple birch homologous trees need further investigation. We hypothesize that birch pollen extract AIT modulates a highly cross-reactive immune response and that this may be the basis for the observed clinical cross-protection. METHODS: Blood samples were collected from 397 birch allergic patients during SQ tree SLIT-tablet or placebo treatment (1:1) for up to 40 weeks. Serum IgE and IgG4 specific to birch, and birch homologous tree pollens from alder, hazel, hornbeam, beech and chestnut were measured by ImmunoCAP. IgE-Blocking Factor (IgE-BF) for alder, birch and hazel during treatment was measured by Advia Centaur and blocking effects for birch and all these birch homologous tree pollens were further investigated by basophil activation (BAT). Antibody readouts were investigated in patient subsets. T-cell responses (proliferation) to allergen extracts and peptide pools (group 1 allergens) were investigated in T-cell lines from 29 untreated birch pollen-allergic individuals. RESULTS: Significant Pearson correlations between serum IgE towards birch, alder, hazel, hornbeam and beech were observed (r-values > .86). T-cell reactivity was observed throughout the birch homologous group. Almost identical kinetics for changes in IgE towards birch, alder and hazel were observed during treatment and similar species-specific changes were seen for serum-IgG4 . IgG4 reactivity towards birch and alder, hazel, hornbeam and beech correlated significantly at end-of-treatment (r-values > .72). Treatment resulted in similar IgE-BF kinetics for alder, birch, and hazel and blocking of BAT for multiple trees in most actively treated patients investigated. CONCLUSIONS: Systematic analyses of T-cell and antibody cross-reactivities before and during birch pollen extract AIT provide the immunological basis for the observed clinical effect of SQ tree SLIT-tablet treatment of tree pollen allergy induced by multiple trees in the birch homologous group.

Effects of atmospheric pollutants (CO, O3, SO2) on the allergenicity of Betula pendula, Ostrya carpinifolia, and Carpinus betulus pollen.

Pollen of Betula pendula, Ostrya carpinifolia, and Carpinus betulus was exposed in vitro to relatively low levels of the air pollutants, namely carbon monoxide, ozone, and sulfur dioxide. The allergenicity of the exposed pollen was compared with that of non-exposed pollen samples to assess if air pollution exposition affects the allergenicity potential of pollen. The immunodetection assays indicated higher IgE recognition by all sera of allergic patients to the pollen protein extracts in all exposed samples in comparison to the non-exposed samples. These results show that the pollen exposition to low pollutants' levels induces increased allergic reaction to sensitized individuals.

Effects of traffic air pollution and hornbeam pollen on adult asthma hospitalizations in Zagreb.

BACKGROUND: Environmental factors play an important role in asthma morbidity, although the contribution of individual pollutants or pollens in exacerbating asthma is not completely elucidated. Despite the evidence of importance of the hornbeam pollen in inducing allergic sensitization, its role in provoking asthma exacerbation has not been evaluated. The aim of the present study was to investigate effects of traffic pollutants on adult asthma hospitalization adjusting for pollens including hornbeam. METHODS: During a 3-year period, health and environmental data were collected and analyzed. Daily asthma hospitalizations were regressed on pollutants and potential confounding variables using an autoregressive Poisson model. RESULTS: The risk of asthma hospitalization was associated significantly with the 95th to 99th percentile increase in levels of nitrogen dioxide (RR = 1.22; 95% CI: 1.05-1.40), carbon monoxide (RR = 1.25; 95% CI: 1.01-1.55) and hornbeam pollen (RR = 1.21; 95% CI: 1.11-1.30). The effect of nitrogen dioxide was delayed by 5 days. No statistically significant increase in the risk of asthma hospitalization was found for PM(10) particles. A comparison among the standardized regression coefficients and their respective p values indicates that the most important risk factor for asthma hospitalization is associated with hornbeam pollen levels. No statistically significant interactions between pollutants and pollens were detected. CONCLUSIONS: The current results suggest that traffic-related air pollution is associated with increased risk of adult asthma hospitalization. Nonetheless, the most significant risk for asthma hospitalization is associated with hornbeam pollen levels in the city of Zagreb.

Immunologic characterization of isoforms of Car b 1 and Que a 1, the major hornbeam and oak pollen allergens.

BACKGROUND: Birch pollen allergy is one of the most common causes of spring pollinosis often associated with hypersensitivity reactions to pollen of other Fagales species. Yet, only the major disease eliciting allergens of alder and hazel have been fully characterized. Therefore, the aim of this study was to perform cloning, expression and immunologic characterization of the Bet v 1 homologues from oak (Que a 1) and hornbeam (Car b 1). METHODS: The isoform pattern of Car b 1 and Que a 1 was analyzed by proteomics using 2D gel electrophoresis and LC ESI-QTOF MS. Isoallergens showing high IgE-binding were cloned and expressed in Escherichia coli. IgE-binding activity of the recombinant proteins was determined by enzyme-linked immunosorbent assay (ELISA) and basophil mediator release assays using serum samples from patients mainly exposed either to oak and hornbeam or to birch pollen. Cross-reactivity of the allergens was further investigated at the T-cell level. RESULTS: Dominant isoforms of Car b 1 and Que a 1, identified by mass spectrometry, showed different IgE-binding properties when testing Fagales pollen-allergic patients living in birch-free areas as compared to birch-sensitized individuals. CONCLUSION: Tree pollen-allergic patients who are primarily exposed to Fagales pollen other than birch reacted stronger with rCar b 1 and rQue a 1 than with rBet v 1, as determined by inhibition ELISA and basophil mediator release assays. Thus, rCar b 1 and rQue a 1 allergens should be considered for improving molecule-based diagnosis and therapy of tree pollen allergies manifesting in birch-free areas.

Associations among pollen sensitizations from different botanical species in patients living in the northern area of Madrid.

OBJECTIVE: To determinate the existence of associations among sensitizations to antigens produced by pollen grains of different botanical species as assessed by skin prick tests in patients with respiratory disorders. METHODS: Six hundred twenty nine consecutive patients living in the northern area of Madrid who underwent clinical evaluation because of rhinoconjunctivitis, and/or asthma were studied. All patients were tested with a skin prick test using a battery of inhalants including pollens, dust mites, molds and danders. The exploratory multivariate technique of Multiple Correspondence Analysis was used to compare the homogeneity of sensitizations between groups. Of the 629 patients, 459 (73.0%) had positive skin prick tests to pollen and were selected as the study group. RESULTS: The most prevalent pollen sensitization was to Gramineae pollen (83.7%) followed by Oleaceae sensitisation (75.8%). Multiple Correspondence Analysis revealed the existence of an association among pollen sensitizations, showing that they clustered two groups: sensitizations to Gramineae, Oleaceae, Cupressaceae, Chenopodiaceae, Plantaginaceae (group I), and sensitizations to Betulaceae, Platanaceae, Compositae (group II). Sensitization to Parietaria was not included in any of the sensitization groups and showed an independent behaviour. CONCLUSION: Pollen sensitizations in our area cluster into two association groups which have not previously been reported.

Incidence of Betulaceae pollen and pollinosis in Zagreb, Croatia, 2002-2005.

Pollen allergy is characterized by seasonal allergic manifestations affecting patients during the plant pollen season. The aim of this study was to analyze the Betulaceae pollen pattern in Zagreb (2002-2005) and to determine the incidence of sensitization to these pollen types in patients with seasonal respiratory allergy. Twenty-four-hour pollen counts were carried out using volumetric procedure. Skin prick test were performed on a total of 864 patients aged 18-80< in Zagreb between 2 January-31 December 2004. Pollen of the representatives of the family Betulaceae accounted for a significant proportion of total pollen (34% on an average), predominated by Betula pollen and considerably lower proportion of Alnus sp. and Corylus sp. pollen. Alder and hazel pollen first occurred in the air in February throughout the study period. The highest airborne pollen concentration of these taxa was recorded in February and March. The birch pollen season generally peaked in April. Only 2.67% of patients showed birch pollen monosensitization. The proportion of patients with polysensitization to Betulaceae pollen was considerably greater (12.88%), whereas polysensitization to Betulaceae, Poaceae and Ambrosia pollen was recorded in the highest proportion of patients (26.23%). According to age, the highest and lowest rate of allergy was recorded in the 31-50 and >51 age groups, respectively (46.22% vs 23.12%). Female predominance was observed across all age groups. The patients with monosensitization to birch pollen had the most severe symptoms in April. In the patients with poylsensitization to alder, hazel and birch pollen who developed cross-reaction, initial symptoms occurred as early as February, with abrupt exacerbation in March and April. The most severe condition was observed in the patients allergic to birch, hazel, alder, grass and ragweed pollen, with symptoms present throughout the year and exacerbation in spring and late summer months.

Correlation of oral allergy syndrome due to plant-derived foods with pollen sensitization in Japan.

BACKGROUND: The clinical features of patients with oral allergy syndrome (OAS) due to plant-derived foods related to pollen allergy have been rarely reported in Japan. OBJECTIVES: To evaluate the characteristics of OAS and to investigate whether pollen sensitizations are correlated with the prevalence of OAS in Japan. METHODS: We measured specific IgE antibodies against 5 pollens in 622 outpatients (277 males and 345 females; mean age, 37 years) with atopic dermatitis, urticaria, angioedema, and food allergy during a 2-year period. Furthermore, OAS is diagnosed based on anamnesis and positive skin prick test reactions to suspected foods. RESULTS: Eighteen of the 436 patients (4.1%) sensitized to pollens were diagnosed as having OAS. Rates of specific IgE antibody-positive responses against Japanese cedar, ragweed, orchard grass, mugwort, and alder pollen were 69.8%, 35.3%, 29.1%, 24.1%, and 19.6%, respectively. The prevalence of OAS showed a significant positive correlation with sensitization to alder (P < .001). In addition, the most frequent causative foods were found to be apple, peach, and melon. The prevalence of OAS due to apple showed a significant positive correlation with sensitization to alder (P < .001) pollen, due to peach showed a significant positive correlation with sensitization to alder (P < .001) and orchard grass (P < .05) pollen, and due to melon showed a significant positive correlation with sensitization to alder (P < .005), orchard grass (P < .05), and ragweed (P < .05) pollen. CONCLUSION: Sensitization to pollens from species in the Betulaceae family is most strongly implicated in causing OAS in Japan.

Immunological characteristics of subjects with asymptomatic skin sensitization to birch and grass pollen.

BACKGROUND: Asymptomatic skin sensitization (AS) has been shown to be a risk factor for respiratory allergic disease. OBJECTIVE: We investigated allergen and recall antigen-driven T cell proliferation, cytokine production and T cell expression of the chemokine receptor CCR4, in cultures derived from symptomatic atopics (SA), subjects with AS and healthy controls (HC). Numbers of allergen-specific precursor T cells in all three groups were also estimated. METHODS: Peripheral blood mononuclear cells from the three groups were isolated and stimulated with allergen and tetanus toxoid. Proliferation, cytokine production and CCR4 expression were measured by flow cytometry. RESULTS: A significantly increased proportion of CD4(+) memory T cells proliferated in response to allergen in SA as compared with subjects with AS (P<0.001) and HC (P<0.001). Only in SA was expansion of CD4(+)CCR4(+) T cells, after allergen stimulation observed. SA had higher frequencies of allergen-specific T cells than subjects with AS and HC (P=0.02, for both). With regard to allergen-induced production of T-helper type 1 (Th1) and Th2 cytokines, subjects with AS and HC resembled each other, while differing significantly from SA. CONCLUSION: We conclude, that subjects with AS, although clearly IgE sensitized, have significant diminished numbers of allergen-specific T cells as well as decreased allergen-induced CD4(+) memory T cell proliferation as compared with SA. To a large extent, our findings are capable of explaining the immunological characteristics associated with AS. Our findings may serve as better prognostic markers for subsequent allergic progression, than previously described clinical and paraclinical characteristics.

Fagales pollen sensitization in a birch-free area: a respiratory cohort survey using Fagales pollen extracts and birch recombinant allergens (rBet v 1, rBet v 2, rBet v 4).

BACKGROUND: Birch allergy is one of the most common pollinosis in areas where exposure to high levels of birch pollen is common. Little is known about birch sensitivity in areas without birch pollen exposure and reactivity to birch-related species within the Fagales order. OBJECTIVE: the aim was to evaluate Fagales reactivity within a population not exposed to birch pollen using epidemiological, diagnostic, and laboratory approaches by means of extracts and allergenic molecules. METHODS: A cohort of 5335 respiratory allergic patients was screened by means of skin testing birch, hazel, and oak pollen extracts. Patients were from a birch-free area, but exposed to other Fagales pollen species. A subset of patients was from an intensively cultivated hazel area. A sample of the Fagales allergic population was tested with other Fagales pollen extract (alder, hornbeam, beech, chestnut) and with apple and hazelnut. IgE detection was performed with birch, hazel, oak, apple, and hazelnut extracts, and with Bet v 1, Bet v 2, Bet v 4, and bromelain. IgE immunoblots were performed using birch and hazel extracts. Epidemiological, clinical, and laboratory data were analysed by stratifying the allergic population. RESULTS: Twenty-five percent of the pollen allergic cohort was skin test positive to at least one of the three Fagales species. Combined reactivity to the three species was recorded in 80% of this cohort. Isolated hazel pollen reactivity was recorded in 13.5% of the Fagales allergic patients. Sixty-six percent of these subjects were from the intensively cultivated hazel area. Reactivity to apple and hazelnut was detected by skin test (40%) and IgE reactivity (60%), but only 19% of the positive patients reported symptoms related to at least one of the two foods. Reactivity to Bet v 1 was recorded in 84% of the birch/hazel/oak co-reactivity group, and in 28% of the subjects with the same co-reactivity, but associating a multiple pollen sensitization. IgE to Bet v 2 (50%) and Bet v 4 (23%) panallergens were recorded positive in the latter subset. Bet v 1 prevalence ranged between 48% and 21% among subgroups of patients coming from different areas. Furthermore, an IgE reactivity to hazel-restricted allergenic components was detected among subjects coming from the same area and having a hazel isolated reactivity. CONCLUSION: Fagales allergy can be found in birch-free areas caused by the exposure to other Fagales species. Birch allergens can be useful for mimicking the allergenic extract, but are also the exclusive tools for a fine diagnostic and epidemiological approach to Fagales pollen allergy. Allergenic molecules from the hazel family will increase the panel of available reagents for the molecule-based approach to allergy diagnosis and therapy.