Therapeutic potential of peptides from Ole e 1 in olive-pollen allergy.

Olive-pollen allergy is one of the leading causes of respiratory allergy in Mediterranean countries and some areas of North America. Currently, allergen-specific immunotherapy is the only etiophatogenic treatment. However, this approach is not fully optimal, safe, or effective. Thus, efforts continue in the search for novel immunotherapy strategies, being one of the most promising the use of peptides derived from major allergens. This work tries to determine the therapeutic potential and safety of 5 dodecapeptides derived from the main allergen of olive-pollen allergy, Ole e 1. The immunomodulatory capacity of these peptides was studied using peripheral blood mononuclear cells (PBMCs) obtained from 19 olive-pollen-allergic patients and 10 healthy controls. We determined the capacity of these peptides to inhibit the proliferative response toward olive-pollen allergenic extract and to induce the regulatory cytokines, IL-10 and IL-35. To test the safety and absence of allergenicity of the peptides, the basophil activation was analyzed by flow-cytometry, using peripheral blood. The results showed that two of five peptides inhibited near to 30% the proliferative response against the total olive-pollen allergenic extract in olive-pollen-allergic patients. Inhibition increased to nearly 35% when the 5 peptides were used in combination. In both cases, a statistically significant induction of IL-10 and IL-35 secretion was observed in the supernatants of allergic patients PBMCs cultures. None of the 5 peptides induced basophil activation and cross-link inflammatory cell-bound IgE. In conclusion, these results open up new possibilities in the treatment of olive-pollen allergy, which could solve some of the problems facing current therapy approaches.

Delineation of the Olive Pollen Proteome and Its Allergenome Unmasks Cyclophilin as a Relevant Cross-Reactive Allergen.

Olive pollen is a major allergenic source worldwide due to its extensive cultivation. We have combined available genomics data with a comprehensive proteomics approach to get the annotated olive tree (Olea europaea L.) pollen proteome and define its complex allergenome. A total of 1907 proteins were identified by LC-MS/MS using predicted protein sequences from its genome. Most proteins (60%) were predicted to possess catalytic activity and be involved in metabolic processes. In total, 203 proteins belonging to 47 allergen families were found in olive pollen. A peptidyl-prolyl cis-trans isomerase, cyclophilin, produced in Escherichia coli, was found as a new olive pollen allergen (Ole e 15). Most Ole e 15-sensitized patients were children (63%) and showed strong IgE recognition to the allergen. Ole e 15 shared high sequence identity with other plant, animal, and fungal cyclophilins and presented high IgE cross-reactivity with pollen, plant food, and animal extracts.

Molecular sensitization patterns and influence of molecular diagnosis in immunotherapy prescription in children sensitized to both grass and olive pollen.

BACKGROUND: The overlapping grass and olive pollen seasons in Spain and the phenomenon of cross-reactivity can make it difficult to determine the true causative agent of seasonal allergic rhinitis when only skin prick tests with whole extracts are used. The aim of the GRAMOLE study was to determine sensitization patterns to the major grass and olive pollen allergens detected using specific recombinant IgE and to explore how this knowledge affected physicians' choice of allergen-specific immunotherapy. METHODS: Epidemiological, observational, multicenter, cross-sectional study. Results from children under 18 years of age diagnosed with seasonal allergic rhinitis by positive skin prick tests to olive and grass pollen were analyzed. Specific IgE to Phl p 1+5, Ole e 1, and Phl p 7+12 was determined. Investigators specified the optimal composition of allergen immunotherapy before and after knowing the results of the molecular diagnosis. RESULTS: A total of 281 patients with a mean age of 13.4 years were included. Double sensitization to both major allergens was found in vitro in 76% of children for an IgE cutoff point of 0.35 kU/L. When the molecular diagnosis results were known, specialists changed the composition of the prescribed immunotherapy in 52.87% of cases. CONCLUSIONS: Double sensitization to grass and olive pollen is common in Spain and also occurs in the pediatric population. Molecular diagnosis using specific IgE may help improve immunotherapy selection in polysensitized patients.

A red yeast rice-olive extract supplement reduces biomarkers of oxidative stress, OxLDL and Lp-PLA2, in subjects with metabolic syndrome: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Metabolic syndrome (MetS) refers to clustered cardiovascular risk factors (abdominal obesity, pre-diabetes, high blood pressure, dyslipidaemia). Therapies targeting oxidative stress may delay progression to atherosclerosis and diabetes. We investigated the anti-oxidative effect of a supplement combining red yeast rice and olive extract in patients with MetS. METHODS: A double-blind, placebo-controlled, randomised trial was conducted with 50 patients with MetS as defined by National Cholesterol Education Program Adult Treatment Panel III criteria. Forty-nine subjects randomly assigned to red yeast rice-olive extract (RYR-olive extract; 10.82 mg of monacolins and 9.32 mg of hydroxytyrosol per Cholesfytolplus capsule) or placebo completed the 8-week trial. Whereas effects on cardiovascular risk parameters of MetS have been reported recently, the observed significant 20% increase in oxidised low-density lipoprotein (OxLDL) prompted us to investigate other oxidative stress-related parameters: malondialdehyde (MDA), lipoprotein-associated phospholipase A2 (Lp-PLA2) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Statistical calculations included univariate quantitative analysis, multivariate linear regression and correlation analysis. RESULTS: The updated results indicate that an RYR-olive extract supplement significantly reduced Lp-PLA2 by 7% (p < 0.001), but it failed to show a significant decrease in plasma MDA and 8-OHdG (p > 0.05). Reductions in OxLDL (20%) and Lp-PLA2 (7%) were associated with each other (r = 0.740, p < 0.001). CONCLUSIONS: RYR-olive extract significantly reduced Lp-PLA2 in correlation with the marked reduction in plasma OxLDL, which may lead to a reduced risk for cardiovascular disease in patients with MetS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02065180 . Registered on 13 February 2014.

Hibiscus Sabdariffa L. Flowers and Olea Europea L. Leaves Extract-Based Formulation for Hypertension Care: In Vitro Efficacy and Toxicological Profile.

Olea europaea L. leaves extract (Oe) and Hybiscus sabdariffa L. flowers extract (Hs) have calcium antagonistic properties. Aim of this work was to study the cardiovascular effects of Pres Phytum(®), a nutraceutical formulation containing a mixture of the two extracts and the excipients, and investigate its possible off-target effects, using in vitro biological assays on guinea pig isolated organs. Cardiovascular effects were assessed using guinea pig atria and aorta. The effects of Pres Phytum on spontaneous gastrointestinal, urinary, and respiratory tracts smooth muscle contractility were evaluated. Pres Phytum exerted a vasorelaxant effect (IC50 = 2.38 mg/mL) and a negative chronotropic effect (IC50 = 1.04 mg/mL) at concentrations lower than those producing smooth muscle spontaneous contractility alterations in the other organs. Compared to Pres Phytum, the mixture did not exert negative inotropic activity, while it maintained a negative chronotropic efficacy (IC50 = 1.04 mg/mL). These experimental data suggest a possible nutraceutical use of this food supplement for the management of preclinical hypertension.

Immunologic responses to the major allergen of Olea europaea in local and systemic allergic rhinitis subjects.

OBJECTIVE: To evaluate the in vivo and in vitro responses to nOle e 1 in allergic rhinitis (AR) and local allergic rhinitis (LAR) patients sensitized to olive tree pollen (OL) confirmed by nasal allergen provocation test (NAPT). METHODS: Twelve subjects with AR, 12 with LAR and 12 subjects as control group (CG) were selected. Skin testing and NAPT with nOle e 1 were performed. Eosinophilic cationic protein (ECP) and tryptase were measured in nasal lavages before and after NAPT. Serum IgE to OL allergens was measured by ELISA. Basophil activation tests (BAT) with OL and nOle e 1 and dendritic cell maturation/proliferation studies were carried out. RESULTS: All AR (12/12) and 10/12 (83%) of LAR had a +NAPT to nOle e 1. ECP levels in nasal lavages were significantly increased after NAPT in both AR and LAR compared with CG at 15 min (P < 0.05). Serum IgE was positive only in AR. All AR had +BAT responses to OL and 10/12 to nOle e 1 (83%); 8/12 LAR (66.6%) had a +BAT to OL and 4/12 (33%) to nOle e 1, with only one subject of the CG with a +BAT to both OL and nOle e 1 (8%). Dendritic cell proliferation to nOle e 1 was increased in AR compared to LAR and CG (P = 0.019 and P = 0.001, respectively). CONCLUSION: Both AR and LAR had a similar in vivo response to nOle e 1 with release of inflammatory mediators. Specific basophil activation with OL and nOle e 1 was observed in LAR confirming previous data obtained with dust mites.

Epigenetic regulation analyses of FOXP3 in olive pollen allergy

No disponible

Olea europaea pollen lipids activate invariant natural killer T cells by upregulating CD1d expression on dendritic cells.

BACKGROUND: Invariant natural killer T (iNKT) cells recognize lipids presented by CD1d and have been implicated in the pathogenesis of allergic asthma. Recognition of plant pollen lipids by iNKT cells and their role in allergic responses are poorly defined. OBJECTIVE: Our goal was to investigate whether iNKT cells can be activated by monocyte-derived dendritic cells (DCs) exposed to lipid antigens from Olea europaea. METHODS: DCs generated in vitro were exposed to O europaea pollen grains or lipids isolated from them. Expression of lipid-presenting molecules (CD1), as well as maturation markers (HLA-DR, HLA-I, CD86, and CD80 molecules), on DCs was analyzed. iNKT cell activation after coculture with DCs was evaluated based on expansion, cytokine production, and cytotoxicity tests. RESULTS: DCs upregulated CD1d and CD86 expression and downregulated CD1a expression after exposure to a whole extract of olive pollen lipids. CD1d and CD1a were regulated at the transcriptional level in a peroxisome proliferator-activated receptor γ activation-dependent manner. Polar lipids, diacylglycerols, free fatty acids, and triacylglycerols isolated from pollen grains upregulate CD1d. The increase in CD1d expression on the DC cell surface induced by polar lipids was not regulated at the RNA level. iNKT cells efficiently recognize DCs treated with the different lipids isolated from olive pollen grains. CONCLUSIONS: Lipids from O europaea pollen upregulate CD1d and CD86 molecules on DCs, which are then able to activate iNKT cells through a CD1d-dependent pathway.

Lower respiratory tract complications during nasal provocation: nonspecific stimulant or specific allergen?

BACKGROUND: Allergic rhinitis (AR) is an allergic inflammatory disease in which allergen exposure leads to the appearance of symptoms in sensitized individuals because of histamine liberation from nasal mucosal mast cells. Comorbidity of this disease with allergic asthma is common. Therefore, the one airway one disease theory has been put forward. Lower respiratory tract provocation tests with both nonspecific (methacholine) and specific stimulants (allergen) have yielded positive results in nonasthmatic patients with AR. However, not enough research is available to demonstrate whether there is a response in the lower respiratory tract during nasal provocation tests (NPTs) performed to evaluate only nasal airway in these patients. OBJECTIVES: To determine if the lower respiratory tract was affected as a result of NPTs with nonspecific and specific stimulants in nonasthmatic patients with AR and to determine the frequency of lower respiratory tract obstruction due to NPT with nonspecific and specific stimulants. METHODS: Thirty-six participants were enrolled in the study between November 2005 and January 2006 (18 AR patients and 18 healthy control subjects). Patients underwent 2 sessions of NPT. The first session was performed with nasal methacholine as a nonspecific stimulant, and the second session was performed with nasal Olea europaea extract as a specific stimulant. The control group underwent only nonspecific nasal provocation with methacholine. Basal nasal opening and nasal pressures were evaluated spirometrically by rhinomanometric measurements and basal respiratory function tests in both groups before methacholine nasal provocation. Whether or not nasal provocation was achieved, spirometric measurements were performed in all patients and controls after NPTs. RESULTS: NPTs with methacholine resulted in a similar frequency of nasal provocation in the patient and control groups (P = .63). However, the mean methacholine dose was lower in patients with AR (P = .049). There was a decrease in parameters of asthma, including the ratio of forced expiratory volume in 1 second to forced vital capacity (P = .04), peak expiratory flow (P = .01), and forced expiratory flow between 25% and 75% (P = .004), as a result of NPTs with methacholine in the patient group. However, NPTs with allergen did not cause a change in lower respiratory tract obstruction criteria. CONCLUSIONS: Lower respiratory tract obstruction can occur after NPTs with nonspecific stimulants; therefore, tests performed with specific allergens can be regarded as safer.

Age, gender and reactivity to allergens independently influence skin reactivity to histamine.

BACKGROUND: The ability to mount an IgE response to allergens is a prerequisite for the development of positive allergen skin tests. Histamine is commonly used as a positive control in skin prick testing and provides a measure of nonspecific skin reactivity, similar to bronchial hyper-responsiveness. METHODS: To determine whether allergen responsiveness, age, gender and season of the year contribute to histamine sensitivity, 620 subjects (502 of them with at least one known sensitizing allergen and the remaining 118 non-allergic controls) were prick-tested with a panel of allergens common in the Northern Italy semi-rural area where the patients lived, and with 10 mg/ml histamine dihydrochloride. RESULTS: We found higher histamine reactivity in allergic versus control individuals (median value 23.7 versus 19.8 mm2; p=0.0497). Likewise, we found in allergic subjects a correlation between allergen responsiveness in terms of number of positive allergens at skin prick test and sensitivity to histamine (mono- sensitized versus poly-sensitized subjects: p=0.0015). Moreover older age and male sex were associated with a higher response to histamine, also when separately considering allergic subjects (p<0.0001 in both cases: correlation coefficient for age versus histamine reactivity: r=0.3408). The correlation between allergen responsiveness and sensitivity to histamine was maintained also when statistically balanced for age and sex. CONCLUSION: Allergen responsiveness, gender and age allow more accurate prediction of histamine sensitivity than either parameter alone.

Sensibilización al polen de Olea europaea en las diferentes comarcas de la provincia de Zamora / Pollen sensitization to Olea europaea in the different regions of Zamora province

La sensibilización al polen de olivo en la provincia de Zamora debería ser mínima debido a que el olivo, por sus características, no se adapta bien a las condiciones climáticas y a que se ha introducido recientemente en la mayoría de las zonas de la provincia como árbol ornamental. Hemos realizado un estudio retrospectivo descriptivo que ha observado una sensibilización llamativa al polen del olivo, que aumenta en las zonas urbanas

Sensitization to olive pollen should not be important in Zamora city and province because, due to its characteristics, this tree doesn´t adapt to weather conditions in the city and because it has been recently introduced in most of the province’s areas as an ornamental tree. We have performed a retrospective descriptive study observing a significant level of sensitization to olive pollen, which is growing in urban zones

Dynamic changes in sensitization to specific aeroallergens in children raised in a desert environment.

BACKGROUND: Allergen skin test reactivity and total serum IgE are objective measures used to characterize and help diagnose allergic diseases. Cross-sectional studies have shown that overall aeroallergen skin test reactivity increases throughout childhood. However, little attention has been paid to whether individual aeroallergen remittance occurs, which could distort or mask relationships to disease. OBJECTIVE: To access the incidence and remittance of skin test reactions to individual allergens in children aged 6-11 years. METHODS: Longitudinal sensitization to six aeroallergens and total IgE were assessed in 828 children raised in the semi-arid US southwest at ages 6 and 11 years. RESULTS: New sensitization (to any allergen) between 6 and 11 years occurred in 30.2% of children compared with 39.7% before age 6 years. The rate of complete remittance from positive to negative between ages 6 and 11 years was 8.2%, and total IgE at age 6 years was not predictive. Remittance rates for individual allergens were high and variable (19-49%). The perennial allergens Bermuda and Alternaria were early sensitizers and had low remittance rates. Early sensitization to the four seasonal allergens was less common and more subject to remittance with the bulk of sensitization occurring between 6 and 11 years. CONCLUSION: This study shows that sensitization to individual aeroallergens in childhood is dynamic and indicates the limitation of single point assessment of skin test reactivity.