Phl P5 Research Articles

Molecular sensitization profile to grass and olive pollens in Portugal.

Background. Grass and olive pollens have overlapping pollination periods and are common allergens in the Iberian Peninsula. The objective is to determine the sensitization pattern to major Phleum pratense and Olea europaea pollens in the Portuguese population with pollen allergic rhinitis (AR) using molecular allergen diagnosis (MAD). Methods. Seasonal AR patients (≥ 12 years), with positive skin prick tests (SPT) to Phleum and Olea were recruited from 16 centers. Using ALEX2, specific IgE to Phl p1, Phl p2, Phl p5, Phl p6, Phl p7, Phl p 12, Ole e1, Ole e7 and Ole e9 were determined. Immunoblotting of Olea allergic patients was performed. Results. Included 175 patients (55.4% female; mean age 31.6 ± 13.3 years; 85.7% adults; 40% asthmatic, Coast 28%/Inland 72% and North 29.1%/Centre 20.6%/South 50.3%). Considering Phleum MAD, 85.7% were sensitized to Phl p1, 45.7% to Phl p2, 50.3% to Phl p5, 45.7%, to Phl p6, 10.9% to Phl p7 and 22.9% to Phl p12. Sensitization to Ole e1 was found in 56.6%, to Ole e7 in 1.7% and Ole e9 in 3.4% patients. Sensitization to Phl p7 was more frequent in asthmatics (17.4% vs 6.6%; p = 0.044). Sensitization to Phl p5, Phl p6, Phl p12 and Ole e1 was more frequent in inland. Regarding sensitization patterns: 53.1% patients were sensitized to both species genuine´ sIgE, 38.3% to Phleum and 3.4% only to Olea species' sIgE. Immunoblotting of Olea allergic patients showed a high intensity band that may correspond to Ole e12. Conclusions. MAD showed "genuine" Grass and Olea sensitization in approximately 50% of our patients.

Sensitization to genuine markers of timothy grass pollen (Phleum pratense) in the North-Central region of Portugal.

Background. Pollen is the main cause of respiratory allergy and its prevalence is increasing. Timothy grass (Phleum pratense) is one of the most common pollen sources, and one of the best characterized allergenic grasses. The major allergens Phl p1, Phl p2, Phl p5 and Phl p6 are considered markers of genuine grass pollen sensitization. Methods. Retrospective study. IgE levels of Phl p1 and Phl p5 in patients living in the North-Central region of Portugal were analyzed, considering age and area of residence (inland or costal). Results. Among the 188 patients with IgE results for Phl p1 and Phl p5, sensitization to Phl p1 and Phl p5b was observed in 97.87% and 63.83%, respectively. The majority demonstrated co-sensitization to both Phl p1 and Phl p5b, while 68 patients were monosensitized to Phl p1 and 4 patients were monosensitized to Phl p5b. Either patients living in costal or inland areas showed IgE levels of Phl p1 higher than Phl p5b. Conclusions. Regarding genuine grass pollen sensitization, Phl p1 sensitization is more prevalent than Phl p5b in the North-Central region of Portugal.

PREVALENCE OF SENSITIZATION TO AIRBORNE ALLERGENS IN PATIENTS WITH ALLERGIC RHINITIS AND ASTHMA IN UKRAINE

Background. The distribution of sensitization among children and adolescence with allergic rhinitis (AR) and asthma and their impact on various allergic symptoms have been analyzed.
 Aim: investigate the distribution of sensitization among children with AR and asthma of the Ukrainian population.
 Material and methods. The study involved 280 children with AR and asthma aged 2–18 years. They were tested for sIgE on the most common allergens among Ukrainians - Dermatophagoides pteronyssinus, Dermatophagoides farinae, dog, cat, cockroach, birch (t03, Bet v1, Bet v2, Bet v4), plane tree, timothy (g06, Phl p1, Phl , Phl p6, Phl p7, Phl p12), ragweed, mugwort and Alternaria. Measurements of sIgE were performed by Western blotting according to the manufacturer's protocol (Simesta-Medivis, Ukraine-Germany).
 Results. Among the sensitized subjects, 165 were sensitive to pollen allergens, sIgE was positive to birch in 64 subjects (22.5%), to mugwort ‒ 65 subjects (25.4%), ragweed ‒ 110 subjects (42.5%), timothy ‒ 69 subjects (24.6%), plane tree ‒ 12 subjects (5%). Positive sIgE to feline allergen was found in 114 (43.3%), dogs ‒ 77 (32.1%), Dermatophagoides pteronyssinus ‒ 66 (24.6%), Dermatophagoides farinae ‒ 32 (12%), Alternaria ‒ 38 (15 %), cockroaches ‒ 25 (10%).
 Conclusions. Sensitization to airborne allergens is significantly associated with asthma and AR. The most important inhalant allergens consist of pollens (trees, grasses, and weeds), house dust mites, molds and animal dander. Among sensitive subjects to pollen allergens, allergy to ragweed was most spread.

Причинно-значимые аллергены и спектр сенсибилизации детей, перенесших пищевую анафилаксию

Aim: to assess the spectrum of sensitization and reveal causative allergens in Ekaterinburg children with the clinical history of food-induced anaphylaxis (FIA) for reducing the number of life-threatening food allergy (FA) episodes in these children. Patients and Methods: the study included 60 children — 36 (60.0%) boys and 24 (40.0%) girls aged from 4 months to 16 years who lived in Yekaterinburg. All children had (FIA) episodes in their clinical histories. The children underwent physical examination, and their allergy- focused clinical history was taken. Also, the ISAC-112 ImmunoCAP assay, a multiplex test with allergen components, was used. Results: the sensitization was assessed, and the causative allergens were identified in 100% of cases. In 31 children (51.67%) FIA was initiated by milk proteins (Bos d4, Bos d5, Bos d8); in 10 (16.67%) – chicken egg (Gal d2, Gal d1); in 10 (16.67%) – walnut (Jug r1, Jug r2, Jug r3); in 9 (15.00%) – fish (Gad c1); in 7 (11.67%) – kiwi (Act d1); in 7 (11.67%) – peanut (Ara h1, Ara h2, Ara h3, Ara h6); and in 20 (33%) – by different nuts (Ber e1, Ana o2, Cora 9, Cora 8). Elevated specific immunoglobulin E (sIgE) levels for birch tree allergens (Bet v1) were found in 39 (65.00%) patients, cat allergens (Fel d1, Fel d2, Fel d4) – in 41 (68.33%), dog allergens (Can f1, Can f2, Can f3, Can f5) – in 24 (40.0%), timothy allergens (Phl p1, Phl p4, Phl p5) – in 10 (16.6%), artemisia allergens (Art v1) – in 8 (13.3%), and house dust mites in 2 (3.33%). Respiratory symptoms in sensitized children with FIA developed in 4 of 5 cases. Conclusion: to reduce the number of life-threatening FA episodes in children with FIA it is necessary to reveal and assess the entire spectrum of sensitization, identify the causative allergens and triggers of potential anaphylactic reaction for the further development of an elimination diet and individualized patient management plan. KEYWORDS: food allergy, food-induced anaphylaxis, children, allergens, sensitization. FOR CITATION: Lepeshkova T.S. Causative allergens and sensitization spectrum in children with the history of food-induced anaphylaxis. Russian Medical Inquiry. 2023;7(2):75–80 (in Russ.). DOI: 10.32364/2587-6821-2023-7-2-75-80.

Профіль сенсибілізації до алергенних компонентів у пацієнтів з респіраторною алергічною патологією

Abstract. Respiratory allergic diseases, which include allergic rhinitis and bronchial asthma, are a serious medical and social problem worldwide due to their high prevalence and negative impact on the quality of life of the relevant category of patients. The development of respiratory allergy pathology is usually caused by inhaled allergens, which are divided into seasonal: tree, grass or weed pollen, as well as year-round — house dust mites, mold, pet epithelium. But at the same time, respiratory manifestations of allergic pathology are often combined with its non-respiratory manifestations, which affects the profile of sensitization of patients to various allergens and requires a personalized approach to specific allergy diagnostics and immunotherapy. The aim of this study was to study the profile of sensitization to the components of various allergens in patients with respiratory allergic pathology. Materials and methods. The results of a multiplex study (determination of specific IgE to 112 allergenic proteins using the ImmunoCap ISAC test system) in 291 patients who applied to the Clinic of Allergology and Immunology “Forpost” with signs of respiratory allergic pathology were analyzed. Results. Among the seasonal allergens, the most frequent causes of sensitization were spring tree proteins (PR10) — Bet v1, timothy and meadow grasses Phl p1, and ragweed Amb a1. Among year-round allergens, sensitization to the major allergenic component of cats — uteroglobin Fel d1, major components of house dust mites and mold fungi Alternaria alternata was most often detected. Among the allergenic proteins of dogs, sensitization to urinary kallikrein Can f5 was most common. The vast majority of examined patients also had sensitization to food allergens of three main groups of proteins — thermolabile proteins (PR10), lipid transport proteins (LTP), or tropomyosin. Conclusions. In the structure of sensitization among adult patients, the main components of pollen allergens of spring trees (Bet v1), meadow grasses (Phl p1) and ragweed (Amb a1) play an important role. Year-round allergens include cat allergens (Fel d1), house dust mites (Der р1, Der f1, Der p2, Der f2) and Alternaria alternata mold (Alt a1). In patients with hypersensitivity to dog and house dust mite allergens, it is necessary to determine the presence of antibodies to such important components as Can f5 and Der p23. Sensitization to minor components of allergens was detected much less often, however, the appropriate determination of antibodies to them is also important, as it affects the choice of patient treatment tactics. Sensitization to food products in persons with respiratory allergic diseases is due to cross-properties of inhaled and food allergens due to PR10, LTP and tropomyosin molecules.

Component-Resolved Diagnosis for Endotyping Patients with Chronic Rhinosinusitis with Nasal Polyps

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammation-mediated disease of the nasal mucosa and paranasal sinuses that often coexists with asthma. The role of atopy in the development and severity of CRSwNP is still a controversial issue. Objective: The aim of our study was to propose a systematic allergy workup to identify atopic patients in the context of CRSwNP and to characterize their allergen sensitization profile (sources/molecules). Methods: Patients with a diagnosis of CRSwNP (n = 97) were studied in the otorhinolaryngologist and allergy settings. Demographic and clinical data were collected for each patient. Different allergen sensitization profiles (sources/molecules) were evaluated in atopic CRSwNP patients by using component-resolved diagnosis (CRD). Results: In our cohort of patients, the CRSwNP was frequently diagnosed during adulthood with significant impact on health-related quality of life. Asthma and atopy were the most common comorbidities with a prevalence of asthma in the atopic group. In CRSwNP patients sensitized to grass pollens and/or to house dust mites, the CRD analysis revealed a prevalence of sensitization to species-specific allergens of Phleum pratense (Phl p1, Phl p2, and Phl p5) or Dermatophagoides pteronyssinus (Der p1 and Der p2) rather than to cross-reactive ones. Conclusion: To define the allergen sensitization profile in atopic CRSwNP patients by CRD, it may be useful to better characterize type 2 inflammation, thus providing a personalized endotype-driven treatment.

Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy

There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT). We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial. Nasal fluid and serum were obtained yearly (per-protocol population, n= 84). TGP-specific IgA1, IgA2, IgG4, IgG, and IgE were measured in nasal fluids by ELISA. TGP-specific IgA1, IgA2, and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively. At years 2 and 3, TGP-IgA1/2 levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA1, 2.0- and 1.8-fold for IgA2, respectively; all P< .01). TGP-IgA1 level in serum was elevated in SLIT compared with SCIT at years 1, 2, and 3 (4.6-, 5.1-, and 4.7-fold, respectively; all P<.001). Serum TGP-IgG level was higher in SCIT compared with SLIT (2.8-fold) at year 2. Serum TGP-IgG4 level was higher in SCIT compared with SLIT at years 1, 2, and 3 (10.4-, 27.4-, and 5.1-fold, respectively; all P< .01). Serum IgG4 levels to Phl p1, 2, 5b, and 6 were increased at years 1, 2, and 3 in SCIT and SLIT compared with placebo (Phl p1: 11.8- and 3.9-fold; Phl p2: 31.6- and 4.4-fold; Phl p5b: 135.5- and 5.3-fold; Phl p6: 145.4- and 14.7-fold, respectively, all at year 2 when levels peaked; P< .05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not at year 3 compared with SCIT (2.8-fold; P= .04) and placebo (3.1-fold; P= .02). IgA to TGP and IgE and IgG4 to TGP components stratified participants according to treatment group and clinical response. The observed induction of IgA1/2 in SLIT and IgG4in SCIT suggest key differences in the mechanisms of action.

Nasal reactivity evaluation in children with allergic rhinitis receiving grass pollen sublingual immunotherapy.

Background: The European Academy of Allergy and Clinical Immunology guidelines, strongly recommended allergen immunotherapy (AIT) as an effective treatment to achieve long-term clinical benefits and to modify the natural history of allergic diseases. Sublingual immunotherapy (SLIT) offers the possibility of home administration, which improves patient comfort and compliance. Objective: The primary outcome of this study was to assess the change in nasal reactivity after grass-pollen AIT treatment. Methods: This was a monocentric, prospective, observational study conducted in Rome from September 2016 to June 2018, in the Pediatric Department of Policlinico Umberto I. We enrolled children, ages between 6 and 12 years, with persistent allergic rhinitis (AR), sensitized to grass pollen. At the first visit (V0, September 2016), one group received the first dose of oral immunotherapy for grass-pollen spray buccal and the other group continued only standard therapy. All the patients had nasal specific immunoglobulin I (IgE) assay (Phl p1, Phl p5), active anterior rhinomanometry with a nasal provocation test (NPT), and spirometry. The patients attended two follow-up visits, in May 2017 (V1) and May 2018 (V2), with the same examinations as at V0. Results: During the treatment, we observed, in the treated group, a significant increase in the mean nasal flow compared with untreated children (p < 0.001). In the AIT group, we found an improvement of nasal function and only 21.05% of all the children in the active group with a positive NPT result at V2. In the control group, we found, at V2, a worsening of nasal function, with 89.47% of the children with a positive NPT result. Furthermore, we found a significant reduction of nasal specific IgE levels at the end of the observation period in the treated group. Conclusion: Analysis of our data provided evidence for a clinical effect of SLIT in inducing clinical changes and allergen tolerance in children with AR.

Long-term efficacy of injected allergen immunotherapy for treatment of grass pollen allergy in elderly patients with allergic rhinitis.

Background: The effect of prolonged allergen immunotherapy is still insufficiently known, especially in elderly patients. Objective: The effect after a 3-year course of injected allergen-specific immunotherapy (AIT) for grass pollen allergy in elderly patients with allergic rhinitis was observed. Methods: Thirty-eight elderly patients (mean ± standard deviation, 66.2 ± 2.7 years old) who received preseasonal injected AIT or placebo for grass pollen allergy were monitored for 3 years and compared with a placebo group. The combined symptom medication score (CSMS), serum level of immunoglobulin G4 (IgG4) to phleum pratense 5 (Phl p5) and quality of life were assessed immediately after AIT and 3 years later. Results: After AIT, the CSMS was significantly decreased from 2.15 (range, 1.27-3.00) to 1.13 (range, 0.79-1.36) (p = 0.03) and remained lower (1.41 ± 0.72 versus 2.41 ± 1.11) than that in the placebo group during the 3 years after AIT. Serum-specific IgG4 against increased during the course of AIT and remained at a high level during further observation. Quality of life, based on the Rhinoconjunctivitis Quality of Life Questionnaire, was significantly decreased in the patients who received AIT from 1.51 (95% confidence interval [CI], 1.21-1.84) to 1.01 (95% CI, 0.93-1.87) (p < 0.05) and was decreased to 0.97-1.26 (95% CI, 0.88-1.82) during the 3 years after discontinuation of AIT. Conclusion: A prolonged positive effect after AIT for grass pollen allergy was observed in elderly patients with allergic rhinitis. Further trials are needed to confirm this effect.Clinical trial MC56871/12, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>.

Component resolved diagnosis by recombinant allergens in patients with allergies to inhalants.

Molecular characterization of IgE reactivity of specific individual components of allergenic extracts is now possible due to the technology of recombinant allergens derived from studies of molecular biology of allergic pathology. The identification of the immunoreactivity to single allergenic components in allergic subjects allows to specifically define her/his allergic profile and obtain the so-termed Component Resolved Diagnosis (CRD). Molecular allergens can be classified into those that induce the respiratory allergic reactivity and those that identify the food-related allergic pathology. It is also essential to identify those molecular allergens whose immunoreactivity is able to connect the two clinical conditions: respiratory symptoms and food allergy symptoms. The present study was conducted on 50 patients with a clinical history of hypersensitivity to pollen and/or allergy and positivity to Skin Prick Test. The sera were analyzed in our laboratories and the panel of recombinant allergens was applied in the case of positivity of the specific IgE. Of the 50 patients enrolled, 31 were selected as positive to 4 main pan-allergen Bet v1, Par j2, Art v1 and Phl p1; among these, 14 subjects showed one allergen-specific IgE towards natural extracts of tested foods even in absence of clinical history. CRD allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in: a) resolving genuine vs cross-reactive sensitization in poly-sensitized patients, b) assessing, in selected cases, the risk of severe, systemic vs mild, local reactions in food allergy, and c) identifying patients and triggering allergens for specific immunotherapy (ITS). In light of our results, we believe that the transition from a diagnostic based on the use of allergenic extracts to another one based on the use of single allergenic molecules that is able to define the specific allergenic profile of each patient, seems to be able to revolutionize the allergy diagnosis.

Sensitization to grass allergens: Phl p1, Phl p5 and Phl p7 Phl p12 in adult and children patients in Beja (Southern Portugal)

BackgroundIn Portugal, the pollen types most implicated in respiratory allergy are grasses, olive and parietaria. The knowledge of sensitizations to molecular allergens in children and adults can contribute to better diagnosis and treatment of this pathology. MethodsImmunoCAP singleplex technology was used for molecular allergens and Phadia 250® automatic equipment. g205 (Phl p1); g215 (Phl p5b); g210 (Phl p7); and g212 (Phl p12) allergen determinations were made in 45 patients with positive grass sensitization tests. ResultsThe majority of patients are sensitized to Phl p1 (91%) and Phl p1+/Phl p5−/Phl p7−/Phl p12− was the most dominant profile (40%). In the adult group, the IgE averages for Phl p1 were approximately 10.46, while they were 8.43 for Phl p5, 0.69 for Phl p7, and 0.06 for Phl p12. In the child group, these values were higher: 22.49, 20.23, 3.89, and 0.35, respectively. For allergens Phl p1, Phl p5, and Phl p7, these differences between the child and adult population were not statistically significant (p=0.754, p=0.806 and p=0.102, respectively), but for Phl p12, a statistically significant difference (p=0.018) was observed. ConclusionsIgE antibodies Phl p1 is the most important allergic marker and sensitivities caused by Phl p12 give rise to higher IgE values in children.

Prolonged effect of allergen sublingual immunotherapy to grass pollen

ABSTRACTBackground: The prolonged effect of allergen immunotherapy is unknown, especially in older patients. Objective: The three-year effect of sublingual allergen-specific immunotherapy (AIT) to grass pollen on elderly patients with allergic rhinitis was analyzed.Methods: Thirty-eight elderly patients (63.18 ± 3.12 yrs.) underwent AIT to grass pollen, were monitored for three years and were compared to a placebo group. AIT was performed with the use of an oral Staloral 300 SR grass extract (Stallergens Greer, London, UK) or a placebo. Symptoms and medication scores, represented by the average adjusted symptom score (AAdSS), the serum level of IgG4 to Phl p5 and the quality of life were assessed immediately after AIT and three years later. Results: After AIT, the AAdSS was significantly decreased and remained lower than in the placebo group during the three years after AIT. Serum-specific IgG4 against Phl p5 increased during the AIT trial in the study group. For the three years of observation after AIT, there were no significant changes in specific IgG4 levels against the analyzed allergens in comparison to the results immediately after AIT. The quality of life, based on the Rhinoconjunctivitis Quality of Life Questionnaire, was significantly decreased in patients who received AIT, from 1.83 (95%CI: 1.45–1.96) to 0.74 (95%CI: 0.39–1.92) (p < 0.05) to 0.82 (95%CI: 0.45– 1.04) three years after AIT.Conclusion: A prolonged positive effect after AIT to grass pollen was observed in elderly patients with allergic rhinitis. Further trials are needed to confirm this effect.

Effects of a ceramide-containing water-in-oil ointment on skin barrier function and allergen penetration in an IL-31 treated 3D model of the disrupted skin barrier.

Atopic dermatitis (AD) is a chronically relapsing, pruritic inflammation of the skin with dryness and disturbed skin barrier function. Recently, we established that IL-31 treatment of human 3D skin models resulted in a disrupted skin barrier phenotype resembling AD. In this model, we found that IL-31 interferes with the differentiation of keratinocytes and inhibits the expression of terminal differentiation markers. In the present study, we investigated the effects of a ceramide-containing water-in-oil skin care ointment on the physical skin barrier structure and function in disrupted skin barrier models, generated either by using primary normal human epidermal keratinocytes (NHEK) or HaCaT cells. We observed that the physical skin barrier of the models recovered after daily topical treatment with the ceramide-containing ointment. Topical application of the ointment prevented downregulation of filaggrin and disorganization of other differentiation markers, such as keratin 10 and β4-integrin, as demonstrated by immunohistological analysis. The expression of Ki67 was also upregulated in response to the ointment. Furthermore, functional studies revealed that local application of the ointment diminished the increased uptake of fluorescently labelled recombinant allergens of timothy grass (phl p1) in our model. In conclusion, our data revealed that topical application of a ceramide-containing skin care ointment reduced IL-31 induced impairments of the physical skin barrier and skin barrier function in an in vitro model of the disrupted skin barrier. This standardized model can be utilized in the future to monitor ex vivo effects of various topical therapies on skin morphology, physiology, and gene expression.

Grass pollen production and group V allergen content of agriculturally relevant species and cultivars.

Grass pollen is the main cause of hay fever and allergic asthma in warm temperate climates during summer. The aim of this study was to determine the content of group 5 major allergens in pollen grains of agriculturally important grass species/cultivars. For each cultivar flowering dates and pollen production of cut anthers were observed in the field and in a climate chamber, respectively. An ELISA was used to quantify the group 5 allergens (Phl p5) in pollen extracts which were gained from the grass species Kentucky bluegrass, perennial rye grass, timothy, cocksfoot, annual / Italian rye grass, hybrid rye grass and festulolium. The group 5 allergen content of species varied between 0.01 ng (Kentucky bluegrass) and 0.06 ng (timothy) per pollen grain. On cultivar level the pollen allergenic content differed up to 74-times within the selected grass species. Results from this study might be helpful for the reduction of allergen exposure coming from agriculture grass production e.g. by an adapted grass selection or by the cultivation of grasses with low allergenic content in plant breeding.

The impact of age on serum allergen-specific IgE to inhaled molecular components

BackgroundRespiratory allergy is characterised by an IgE-mediated reaction. The immune system functions, including IgE production, progressively decline over time, such as growing up and ageing. Molecular-based allergy diagnostic defines sensitisation profile. This study aimed to evaluate the impact of age on serum allergen-specific IgE to molecular component levels in a large sample of subjects. MethodsSerum IgE to: Phl p1, Bet v1, Ole e1, Cup a1, Par j2, Can f1, Der p2, and Fel d1 were assessed by ISAC method. Sera from 2788 patients, 1230 males (44.1%) and 1558 females (55.9%), median age 23 years (1st and 3rd quartiles: 9.7–49.7 years; age range: 1 month–103 years) were analysed. ResultsThe number of positive tests (i.e. sensitisation) tended to increase between birth and school-age till young adulthood and then decreased (p<0.0001) with the exception of Fel d 1 (p=0.14). A similar age-dependent trend was observed considering the levels of each allergen components: the levels of each allergen component, with the exception of Fel d 1, tended to increase till early adulthood and then to decrease reaching the lowest levels in the elderly. ConclusionsAllergen-specific IgE production to inhaled molecular components trend to reduce with ageing, but with differences between allergens. This phenomenon should be adequately evaluated managing allergic patients.

Anaphylaxis caused by flaxseed

Methods and results Prick-prick carried out with flaxseed showed a strong positivity. Skin prick test to inhaled allergens were positive to mites, dog and cat danders, plain tree and grasses. Skin prick test to food allergens were positive to almond, hazelnut, peanut, chestnut, walnut, mustard, lentils, soybeans, rice, oat, corn and lupine. Total IgE was: 291 UI/ml. Specific IgE (CAP, ThermoFisher Scientific) to flaxseed was 2.68 kU peach 7.65 kU/L, peanut 2.01 kU / L , lettuce 0.92 kU / L , lupin 3.76 kU / L. Corn IgE 2.71 kU / L , Pru p3 7.62 kU / L , Cor a8 0.68 kU / L. ISAC, ImmunoCAP was positive to Fel d1, Phl p1, Der f1, Der f2, Der p1, Der p2, Pla a3, Ara h9, Cor a8, Jug r3, Pru p3 and Art v3. ISAC performed after inhibit patients’s serum (ISAC inhibition) with a complete flaxseed extract (f233:Linum usitatissium from ImmunoCAP, ThermoFisher Scientific) did not reduced the positivity to non-specific lipid transfer proteins (nsLTP). ISAC inhibition with a complete mite extract (d1: D. pteronyssinus from ImmunoCAP, ThermoFisher Scientific) reduces exclusively the signal of mites (Der f1, Der f2, Der p1, Der p2) in >83%.An immunoblot performed with flaxseed extracts (soluble and liposoluble), showed the presence of an IgE-binding band of about 18 kDa in the liposoluble fraction and a 20 kDa band in the soluble one.

Increased allergen-specific IgG4 levels are linked to suppressed IgE titers when analysed by ISAC but not by immunocap

Allergen specific immunotherapy (ASIT) is the only disease modifying treatment of allergic diseases. A key element in the protective effect is thought to be induction of a specific IgG4 response leading to a decrease in the IgE-mediated allergic symptoms. The effect of ASIT can be ascertained by provocation or skin prick testing. IgE measurement by ImmunoCAP is a sensitive standard procedure for allergy diagnosis and this has recently been supplemented by a single allergen array (ISAC), which employs significantly lower amounts of allergen and may have different assay dynamics. 24 subjects suffering from allergic rhinitis due to grass pollen allergy were stratified on basis of sensitivity in a basophil activation test, to receive standard subcutaneous immunotherapy (n=18) or to an open control group (n=6). Allergen specific IgE and IgG4 was measured at baseline and when reaching maintenance dose by using both the quantitative ImmunoCAP for Phl p1 and Phl p5 and the chip-based semi-quantitative ISAC method (Phl p 1, 2, 4, 5, 6, 7, 11 and 12). Data are presented as mean and 95% CI. ASIT treatment reduced self-reported symptoms from 10,7 to 5,5 (p=0,0001). ASIT increased allergen specific IgG4 levels, both by ISAC (from 0,3 to 5,0 ISAC specific units (ISU) (∆ 4,7 ISU; 2,7-6,7 ISU; p=0,0001) and ImmunoCAP (from 0,1 to 5,2 mg/l, ∆ 5,1 mg/l; 2,3-7,9 mg/ml; p=0,0006). Specific IgE increased from 23,0 to 48,8 kU/l when measured by ImmunoCAP (∆ 25,8 kU/l; 4,4-47,2; p=0,01). Surprisingly, ISAC measurement of specific IgE decreased from 21,4 to 2,5 ISU (∆ 18,9 ISU; -10,0;-27,8; p=0,0002) during updosing. No significant changes in IgG4 or IgE measurements were found in the control group during the treatment period. ImmunoCAP measurements indicate that IgG4 and IgE increase during ASIT updosing as previously reported. In contrast, when IgE in the same serum samples was measured by ISAC a decrease in IgE seems to be the result of successful ASIT. This may be the result of inhibition of IgE-binding in vitro in the ISAC assay, possibly reflecting functional IgE inhibition in vivo in the treated patients. ISAC measurements before and after ASIT may thus be useful in monitoring the clinical effect of allergen specific immunotherapy.

Peptide-induced immune regulation by a promiscuous and immunodominant CD4T-cell epitope of Timothy grass pollen: a role of Cbl-b and Itch in regulation

BackgroundT-cell targeted peptide epitope tolerogens from grass pollen allergens may be useful in treating seasonal allergic rhinitis, but there is urgent need for optimisation of approaches from improved understanding of...

Efficacy of Timothy grass allergy immunotherapy tablet (AIT) treatment in Canadian children and adults with grass pollen-induced allergic rhinoconjunctivitis (ARC)

Methods Subjects 5 years and older with ARC with/without asthma received once-daily 2800 BAU sublingual grass AIT (oral lyophilisate, Phleum pratense, 75,000 SQ-T, ~15μg Phl p5) or placebo starting approximately 16 weeks before and continuing throughout the 2009 grass pollen season (GPS). Subjects used daily e-diaries to record ARC symptoms and use of symptomatic medications from randomization through study end (approximately 24 weeks). The primary efficacy endpoint comprised the average total combined daily symptom and medication score (TCS) during the entire GPS. Secondary endpoints included average daily symptom score (DSS) and average daily medication score (DMS). Safety was assessed by monitoring adverse events (AEs).

Allergen immunotherapy

Specific immunotherapy (SIT) involves the administration of allergen extracts to achieve clinical tolerance of those allergens that cause symptoms in patients with allergic conditions. Immunotherapy is effective in patients with mild forms of allergic disease and also in those who do not respond well to standard drug therapy. Most SIT is given by means of injection, but there is increasing interest in performing SIT through the sublingual route. SIT remains the treatment of choice for patients with systemic allergic reactions to wasp and bee stings and should be considered as an option in patients with allergic rhinitis, asthma, or both. SIT can modify the course of allergic disease by reducing the risk of new allergic sensitizations and inhibiting the development of clinical asthma in children treated for allergic rhinitis. The precise mechanisms responsible for the beneficial effects of SIT remain a matter of research and debate. An effect on regulatory T cells seems most probable and is associated with switching of allergen-specific B cells toward IgG4 production. Few direct comparisons of SIT and drug therapy have been made. Existing data suggest that the effects of SIT take longer to develop, but once established, SIT achieves long-lasting relief of allergic symptoms, whereas the benefits of drugs only last as long as they are continued.