RESUMEN
BACKGROUND: Ragweed (Ambrosia elatior) has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest. OBJECTIVE: This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen. METHODS: We retrospectively reviewed the clinical records of 57 patients during the 2015 and 2016 ragweed pollen seasons. Patients were divided into two groups: Group 1 (n = 29), who had not received immunotherapy, and Group 2 (n = 28), who had previously undergone immunotherapy with another sublingual preparation. All patients were treated with Oraltek® ragweed for 4-6 months, initiating 2-4 months before the pollen season and rest of the period was 2 months of the 2016 pollen season. Symptom score (SS), medication score (MS), and combined symptom and medication score (CSMS) were evaluated intra- and intergroup. RESULTS: Pollen counts were consistent between 2015 and 2016. All patients showed significant improvement in SS, MS, and CSMS, with a large effect size (>0.8). Group 2 had significantly lower SS and CSMS in 2015 because of prior immunotherapy. By 2016, both groups exhibited marked improvements, with Group 1 showing a 75% improvement in CSMS. No local or systemic reactions were recorded, indicating a high safety profile. CONCLUSIONS: Ragweed SLIT significantly improved symptoms and reduced use of medication in patients allergic to ragweed pollen. The treatment was effective even in patients with previous immunotherapy, with a high benefit-risk ratio demonstrated by the absence of adverse reactions. These findings support the use of Oraltek SLIT for managing ragweed pollen allergy.
Asunto(s)
Alérgenos , Ambrosia , Antígenos de Plantas , Rinitis Alérgica Estacional , Inmunoterapia Sublingual , Humanos , Inmunoterapia Sublingual/métodos , Masculino , Femenino , Estudios Retrospectivos , Rinitis Alérgica Estacional/terapia , Rinitis Alérgica Estacional/inmunología , Adulto , Ambrosia/inmunología , Alérgenos/inmunología , Alérgenos/administración & dosificación , Hungría , Antígenos de Plantas/inmunología , Antígenos de Plantas/administración & dosificación , Persona de Mediana Edad , Adulto Joven , Extractos Vegetales/administración & dosificación , Resultado del Tratamiento , Adolescente , Polen/inmunologíaRESUMEN
Ragweed pollen allergy is the most common seasonal allergy in western Romania. Prolonged exposure to ragweed pollen may induce sensitization to pan-allergens such as calcium-binding proteins (polcalcins) and progression to more severe symptoms. We aimed to detect IgE sensitization to recombinant Amb a 9 and Amb a 10 in a Romanian population, to assess their potential clinical relevance and cross-reactivity, as well as to investigate the relation with clinical symptoms. rAmb a 9 and rAmb a 10 produced in Escherichia coli were used to detect specific IgE in sera from 87 clinically characterized ragweed-allergic patients in ELISA, for basophil activation experiments and rabbit immunization. Rabbit rAmb a 9- and rAmb a 10-specific sera were used to detect possible cross-reactivity with rArt v 5 and reactivity towards ragweed and mugwort pollen extracts. The results showed an IgE reactivity of 25% to rAmb a 9 and 35% to rAmb a 10. rAmb a 10 induced basophil degranulation in three out of four patients tested. Moreover, polcalcin-negative patients reported significantly more skin symptoms, whereas polcalcin-positive patients tended to report more respiratory symptoms. Furthermore, both rabbit antisera showed low reactivity towards extracts and showed high reactivity to rArt v 5, suggesting strong cross-reactivity. Our study indicated that recombinant ragweed polcalcins might be considered for molecular diagnosis.
Asunto(s)
Proteínas de Unión al Calcio , Reacciones Cruzadas , Inmunoglobulina E , Rinitis Alérgica Estacional , Adulto , Femenino , Humanos , Masculino , Alérgenos/inmunología , Ambrosia/inmunología , Antígenos de Plantas/inmunología , Proteínas de Unión al Calcio/inmunología , Reacciones Cruzadas/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Extractos Vegetales , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica Estacional/sangre , RumaníaRESUMEN
Pollen from common ragweed is an important allergen source worldwide and especially in western and southern Romania. More than 100 million patients suffer from symptoms of respiratory allergy (e.g., rhinitis, asthma) to ragweed pollen. Among the eleven characterized allergens, Amb a 6 is a non-specific lipid transfer protein (nsLTP). nsLTPs are structurally stable proteins in pollen and food from different unrelated plants capable of inducing severe reactions. The goal of this study was to produce Amb a 6 as a recombinant and structurally folded protein (rAmb a 6) and to characterize its physicochemical and immunological features. rAmb a 6 was expressed in Spodoptera frugiperda Sf9 cells as a secreted protein and characterized by mass spectrometry and circular dichroism (CD) spectroscopy regarding molecular mass and fold, respectively. The IgE-binding frequency towards the purified protein was evaluated using sera from 150 clinically well-characterized ragweed-allergic patients. The allergenic activities of rAmb a 6 and the nsLTP from the weed Parietaria judaica (Par j 2) were evaluated in basophil activation assays. rAmb a 6-specific IgE reactivity was associated with clinical features. Pure rAmb a 6 was obtained by insect cell expression. Its deduced molecular weight corresponded to that determined by mass spectrometry (i.e., 10,963 Da). rAmb a 6 formed oligomers as determined by SDS-PAGE under non-reducing conditions. According to multiple sequence comparisons, Amb a 6 was a distinct nsLTP with less than 40% sequence identity to currently known plant nsLTP allergens, except for nsLTP from Helianthus (i.e., 52%). rAmb a 6 is an important ragweed allergen recognized by 30% of ragweed pollen allergic patients. For certain patients, rAmb a 6-specific IgE levels were higher than those specific for the major ragweed allergen Amb a 1 and analysis also showed a higher allergenic activity in the basophil activation test. rAmb a 6-positive patients suffered mainly from respiratory symptoms. The assumption that Amb a 6 is a source-specific ragweed allergen is supported by the finding that none of the patients showing rAmb a 6-induced basophil activation reacted with Par j 2 and only one rAmb a 6-sensitized patient had a history of plant food allergy. Immunization of rabbits with rAmb a 6 induced IgG antibodies which strongly inhibited IgE binding to rAmb a 6. Our results demonstrate that Amb a 6 is an important source-specific ragweed pollen allergen that should be considered for diagnosis and allergen-specific immunotherapy of ragweed pollen allergy.
Asunto(s)
Alérgenos , Antígenos de Plantas , Proteínas Portadoras , Inmunoglobulina E , Humanos , Alérgenos/inmunología , Inmunoglobulina E/inmunología , Antígenos de Plantas/inmunología , Antígenos de Plantas/química , Animales , Proteínas Portadoras/inmunología , Proteínas Portadoras/metabolismo , Proteínas de Plantas/inmunología , Proteínas de Plantas/química , Femenino , Rinitis Alérgica Estacional/inmunología , Masculino , Adulto , Ambrosia/inmunología , Spodoptera/inmunología , Proteínas Recombinantes/inmunología , Secuencia de Aminoácidos , Células Sf9 , Persona de Mediana Edad , Extractos VegetalesRESUMEN
Common ragweed pollen allergy has become a health burden worldwide. One of the major allergens in ragweed allergy is Amb a 1, which is responsible for over 90% of the IgE response in ragweed-allergic patients. The major allergen isoform Amb a 1.01 is the most allergenic isoform in ragweed pollen. So far, no recombinant Amb a 1.01 with similar allergenic properties to its natural counterpart (nAmb a 1.01) has been produced. Hence, this study aimed to produce a recombinant Amb a 1.01 with similar properties to the natural isoform for improved ragweed allergy management. Amb a 1.01 was expressed in insect cells using a codon-optimized DNA construct with a removable N-terminal His-Tag (rAmb a 1.01). The recombinant protein was purified by affinity chromatography and physicochemically characterized. The rAmb a 1.01 was compared to nAmb a 1.01 in terms of the IgE binding (enzyme-linked immunosorbent assay (ELISA), immunoblot) and allergenic activity (mediator release assay) in well-characterized ragweed-allergic patients. The rAmb a 1.01 exhibited similar IgE reactivity to nAmb a 1.01 in different IgE-binding assays (i.e., IgE immunoblot, ELISA, quantitative ImmunoCAP inhibition measurements). Furthermore, the rAmb a 1.01 showed comparable dose-dependent allergenic activity to nAmb a 1.01 regarding basophil activation. Overall, the results showed the successful expression of an rAmb a 1.01 with comparable characteristics to the corresponding natural isoform. Our findings provide the basis for an improvement in ragweed allergy research, diagnosis, and immunotherapy.
Asunto(s)
Alérgenos , Ambrosia , Antígenos de Plantas , Inmunoglobulina E , Proteínas Recombinantes , Humanos , Antígenos de Plantas/inmunología , Antígenos de Plantas/genética , Antígenos de Plantas/química , Inmunoglobulina E/inmunología , Animales , Alérgenos/inmunología , Alérgenos/genética , Ambrosia/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Femenino , Adulto , Proteínas de Plantas/inmunología , Proteínas de Plantas/genética , Proteínas de Plantas/química , Rinitis Alérgica Estacional/inmunología , Masculino , Persona de Mediana Edad , Extractos Vegetales/químicaRESUMEN
BACKGROUND: Allergic rhinitis with or without conjunctivitis can negatively impact many aspects of quality of life (QoL). The efficacy and safety of standardized quality (SQ) sublingual immunotherapy (SLIT) tablets have been confirmed across large clinical trials in adults with grass, tree, ragweed, and house dust mite (HDM) allergic rhinitis with or without conjunctivitis. OBJECTIVE: This pooled analysis investigates whether the reduction in symptom burden found across the clinical trials is supported by improvements in QoL. METHODS: A total of 11 phase II/III randomized placebo-controlled trials across the SQ grass, tree, ragweed, and HDM SLIT tablets (grass: N = 3179; ragweed: N = 767; tree: N = 634; HDM: N = 2221) were included. QoL was assessed using the standardized Rhinitis Quality of Life Questionnaire (RQLQ), with the exception of 3 grass trials, which used the nonstandardized version. The overall RQLQ scores were expressed as a mean of 7 domains. In the pooled analysis, treatment was used as fixed effect; and the trial, and the interaction between region/country and trial as random effects. RESULTS: The pooled analysis showed consistent and statistically significant improvements in overall RQLQ scores across all 4 SQ SLIT tablets versus placebo (pooled estimate [95% CI], P value-grass: -0.20 [-0.28 to -0.12], P < .001; tree: -0.42 [-0.58 to -0.26], P < .001; ragweed: -0.36 [-0.55 to -0.17], P < .001; HDM: -0.28 [-0.39 to -0.17], P < .001). Furthermore, significant improvements versus placebo for all 4 SQ SLIT tablets were seen across the 7 individual domains. CONCLUSIONS: The proven efficacy of SQ SLIT tablets to reduce symptoms across 4 of the most common respiratory allergens is supported by concurrent significant improvements in RQLQ scores overall and for all 7 domains.
Asunto(s)
Alérgenos , Conjuntivitis Alérgica , Inmunoterapia Sublingual , Adulto , Animales , Femenino , Humanos , Masculino , Alérgenos/inmunología , Ambrosia/inmunología , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Conjuntivitis Alérgica/terapia , Conjuntivitis Alérgica/inmunología , Poaceae/inmunología , Pyroglyphidae/inmunología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Rinitis Alérgica/terapia , Inmunoterapia Sublingual/métodos , Comprimidos , Resultado del Tratamiento , Árboles/inmunologíaRESUMEN
Nineteen U.S. allergen extracts were standardized by the U.S. Food and Drug Administration (FDA) between 1987 and 1998, including of two house-dust mites, short ragweed, cat hair and cat pelt, seven temperate and one southern grass, and six Hymenoptera venom preparations. Relevant literature was reviewed. For each allergen, a "representative" extract was established; the potency of each representative extract was determined by measurement of the total protein content (Hymenoptera venom), radial diffusion measurement of the dominant allergen (short ragweed and cat), or, if there was no dominant allergen, then by quantitative skin testing by using the ID50EAL (intradermal dilution for 50 mm sum of erythema determines the bioequivalent allergy units) method. In vitro tests were developed to allow the manufacturer to demonstrate that each lot of its extract was statistically identical, within defined limits, to the FDA reference extract. These tests included radial immunodiffusion, competitive enzyme-linked immunosorbent assay, and isoelectric focusing. The standardized extracts offer the advantage of consistent potency from lot to lot for each manufacturer and also from manufacturer to manufacturer, and assure the presence of recognized significant allergens within the extract. Therefore, standardized extracts offer improved safety and efficacy over their nonstandardized predecessors.
Asunto(s)
Alérgenos , Venenos de Artrópodos , Desensibilización Inmunológica , Extractos Vegetales , Alérgenos/química , Alérgenos/inmunología , Alérgenos/uso terapéutico , Ambrosia/química , Ambrosia/inmunología , Animales , Venenos de Artrópodos/química , Venenos de Artrópodos/inmunología , Gatos/inmunología , Desensibilización Inmunológica/métodos , Desensibilización Inmunológica/normas , Humanos , Extractos Vegetales/química , Extractos Vegetales/inmunología , Extractos Vegetales/normas , Extractos Vegetales/uso terapéutico , Poaceae/química , Poaceae/inmunología , Pyroglyphidae/química , Pyroglyphidae/inmunologíaRESUMEN
OBJECTIVE: Allergic rhinitis (AR) is an immunoglobulin (Ig) E-mediated inflammatory condition that causes sneezing, nasal congestion, rhinorrhea, and nasal itch. Although subcutaneous immunotherapy for the treatment of AR has been in use and well established as a treatment modality, sublingual immunotherapy (SLIT) is increasingly considered to be the safer and more convenient alternative. Thus, the objective of this review is to describe recent findings pertaining to the use of SLIT tablets (SLIT-T) for AR. DATA SOURCES: A database search (PubMed.gov) for articles published between January 1, 2017, and February 9, 2021, was conducted using the following key words: "allergic rhinitis," AND-ed "sublingual immunotherapy." Included were randomized placebo-controlled trials. Other experimental design studies were excluded. STUDY SELECTIONS: A total of 11 randomized placebo-controlled trials were selected for full-text review and included in the analysis. All studies investigated the use of SLIT on patients with seasonal AR (4 tree pollen, 1 grass pollen, and 1 Japanese cedar) or perennial AR (3 house dust mite). RESULTS: Our review of 7 recently published randomized placebo-controlled trials with 2348 subjects receiving SLIT reported increased efficacy, safety, supportive immunologic parameters (IgE and IgG4 pre- and posttreatment levels), and improved quality of life. All studies excluded subjects with overlapping seasonal or perennial allergens, a history of moderate-to-severe uncontrolled asthma, or reduced lung function. CONCLUSION: Our review highlights that SLIT is a safe and effective treatment that considerably reduces symptoms and medication requirements in AR and improves quality of life.
Asunto(s)
Alérgenos/administración & dosificación , Desensibilización Inmunológica/métodos , Polen/inmunología , Rinitis Alérgica/terapia , Inmunoterapia Sublingual/efectos adversos , Inmunoterapia Sublingual/métodos , Adolescente , Adulto , Anciano , Alérgenos/inmunología , Ambrosia/inmunología , Animales , Antígenos de Plantas/inmunología , Niño , Preescolar , Cryptomeria/inmunología , Humanos , Persona de Mediana Edad , Extractos Vegetales/inmunología , Poaceae/inmunología , Pyroglyphidae/inmunología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto JovenRESUMEN
BACKGROUND: Staphylococcus aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in patients with AD is unclear. OBJECTIVE: We sought to identify the S aureus-derived virulence factor(s) that initiates the cutaneous type 2-promoting immune response responsible for AD. METHODS: In vitro human keratinocyte cell culture, ex vivo human skin organ explants, and the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse were used as model systems to assess type 2-promoting immune responses to S aureus. Identification of the bioactive factor was accomplished using fast protein liquid chromatography and mass spectrometry. Bioactivity was confirmed by cloning and expression in an Escherichia coli vector system, and S aureus second immunoglobulin-binding protein (Sbi) mutant strains confirming loss of activity. RESULTS: S aureus was unique among staphylococcal species in its ability to induce the rapid release of constitutive IL-33 from human keratinocytes independent of the Toll-like receptor pathway. Using the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse model, we showed that IL-33 was essential for inducing the immune response to S aureus in vivo. By fractionation and candidate testing, we identified Sbi as the predominant staphylococcus-derived virulence factor that directly drives IL-33 release from human keratinocytes. Immunohistology of skin demonstrated that corneodesmosin, a component of corneodesmosomes that form key intercellular adhesive structures in the stratum corneum, was disrupted, resulting in reduction of skin barrier function. CONCLUSIONS: S aureus-derived Sbi is a unique type 2-promoting virulence factor capable of initiating the type 2-promoting cytokine activity underlying AD.
Asunto(s)
Proteínas Bacterianas/inmunología , Proteínas Portadoras/inmunología , Dermatitis Atópica/inmunología , Interleucina-33/inmunología , Queratinocitos/inmunología , Staphylococcus aureus/inmunología , Factores de Virulencia/inmunología , Adulto , Alérgenos/inmunología , Ambrosia/inmunología , Animales , Células Cultivadas , Humanos , Ratones , Pyroglyphidae/inmunología , Staphylococcus aureus/patogenicidadRESUMEN
BACKGROUND: The so-called "thunderstorm asthma" (TA) is an uncommon but dramatic outbreak of asthma attacks occurring during a thunderstorm in the pollen and moulds season. Mechanisms which make the pollen able to enter the deeper airways and provoke severe asthma symptoms are still unclear. OBJECTIVE: To test the hypothesis that sub-pollen particles (SPPs) originated from the rupture by an osmotic shock of pollen associated with TA contain allergens. METHODS: After hydration, SPPs released from pollen grains of grass, pellitory, olive, cypress, ragweed and birch were isolated and determined by microscopy. Allergens were determined by in vitro ELISA inhibition tests indirectly using the sera from 10 polyreactive patients. An inhibition <50% was considered as negative, 50%-75% moderate and > 75% complete. RESULTS: The inhibition experiments showed that the SPPs from birch and cypress were unable to inhibit serum IgE reactivity to Bet v 1 and Cup a 1, respectively. Ragweed SPPs inhibited ragweed pollen extract and Amb a 1 by 75.8 ± 0.11% and 81.2 ± 0.15%, respectively. Olive and pellitory SPPs retained almost the whole IgE-binding capability in all cases tested. Grass SPPs inhibited 32 ± 0.06% of Lolium perenne Lol p 1 and 65% of Phleum pratense extracts, but results were highly variable for individual allergens (97.5%-0.03% for Phl p 2, 45.3 ± 0.12% for Phl p 5, 24.7 ± 0.22% for Phl p 6, and 38.3 ± 0.2% for Phl p 1). CONCLUSIONS: Inhibition experiments confirm the hypothesis that SSPs obtained after the osmotic shock of pollen involved in TA, namely grass, pellitory and olive tree pollen, contain allergens and therefore they can induce severe asthma attacks during thunderstorms.
Asunto(s)
Alérgenos/inmunología , Asma/inmunología , Humedad , Presión Osmótica/fisiología , Polen/fisiología , Lluvia , Rinitis Alérgica Estacional/inmunología , Alérgenos/química , Alnus/inmunología , Ambrosia/inmunología , Asma/epidemiología , Asma/etiología , Betula/inmunología , Cupressus/inmunología , Brotes de Enfermedades , Ensayo de Inmunoadsorción Enzimática , Humanos , Pruebas Inmunológicas , Olea/inmunología , Parietaria/inmunología , Phleum/inmunología , Poaceae/inmunología , Polen/química , Polen/inmunología , Rinitis Alérgica Estacional/etiologíaRESUMEN
Mouse models of allergic conjunctivitis mimic various aspects of human allergic conjunctivitis. They are useful as acute models of allergic conjunctivitis to study immunological aspects of this condition. In this chapter, we will describe ragweed-pollen-induced experimental allergic conjunctivitis (mostly driven by adaptive immunity), and papain-soaked contact lens-induced experimental allergic conjunctivitis (mostly driven by innate immunity). Giemsa staining of histological sections is used for quantification of the number of infiltrating eosinophils, which is useful to evaluate the severity of the allergic inflammation. Immunohistochemical staining and quantitative PCR are used to clarify spatiotemporal expression of proinflammatory molecules in the conjunctival tissue. Flow cytometric analysis of conjunctival tissue is used for the detection of innate lymphoid cell type 2 (ILC2) in the ocular surface tissues.
Asunto(s)
Ambrosia/inmunología , Conjuntiva/efectos de los fármacos , Conjuntivitis Alérgica/inmunología , Modelos Animales de Enfermedad , Linfocitos/efectos de los fármacos , Papaína/administración & dosificación , Inmunidad Adaptativa/efectos de los fármacos , Adyuvantes Inmunológicos/administración & dosificación , Alérgenos/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Ambrosia/química , Animales , Biomarcadores/metabolismo , Conjuntiva/inmunología , Conjuntiva/patología , Conjuntivitis Alérgica/inducido químicamente , Conjuntivitis Alérgica/genética , Conjuntivitis Alérgica/patología , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Eosinófilos/patología , Femenino , Citometría de Flujo/métodos , Expresión Génica , Inmunidad Innata/efectos de los fármacos , Inmunoglobulina E/genética , Inmunoglobulina E/inmunología , Interleucinas/genética , Interleucinas/inmunología , Linfocitos/inmunología , Linfocitos/patología , Ratones , Ratones Endogámicos C57BL , Polen/efectos adversos , Polen/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
Sunflower pollen was reported to contain respiratory allergens responsible for occupational allergy and pollinosis. The present study describes the comprehensive characterization of a major sunflower allergen Hel a 6. Natural Hel a 6 was purified from sunflower pollen by anion exchange and gel filtration chromatography. Hel a 6 reacted with IgE-antibodies from 57% of 39 sunflower-sensitized patient sera suggesting it to be a major allergen. The patients were of Indian origin and suffering from pollinosis and allergic rhinitis. Hel a 6 exhibited allergenic activity by stimulating mediator release from basophils. Monomeric Hel a 6 displayed pectate lyase activity. The effect of various physicochemical parameters such as temperature, pH, and calcium ion on the functional activity of Hel a 6 revealed a stable nature of the protein. Hel a 6 was folded, and its melting curve showed reversible denaturation in which it refolded back to its native conformation from a denatured state. Hel a 6 displayed a high degree of sequence conservation with the pectate lyase allergens from related taxonomic families such as Amb a 1 (67%) and Art v 6 (57%). The IgE-cross reactivity was observed between Hel a 6 and its ragweed and mugwort homologs. The cross-reactivity was further substantiated by the mediator release when Hel a 6-sensitized effector cells were cross-stimulated with Art v 6 and Amb a 1. Several putative B cell epitopes were predicted and mapped on these 3 allergens. Two antigenic regions were found to be commonly shared by these 3 allergens, which could be crucial for cross-reactivity. In conclusion, Hel a 6 serves as a candidate molecule for diagnosis and immunotherapy for weed allergy.
Asunto(s)
Alérgenos/química , Alérgenos/inmunología , Helianthus/química , Hipersensibilidad/inmunología , Polisacárido Liasas/inmunología , Alérgenos/aislamiento & purificación , Alérgenos/metabolismo , Ambrosia/inmunología , Dicroismo Circular , Reacciones Cruzadas , Epítopos/inmunología , Granjas , Helianthus/inmunología , Histamina/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Sueros Inmunes , Espectrometría de Masas , Proteínas de Plantas/química , Proteínas de Plantas/inmunología , Proteínas de Plantas/aislamiento & purificación , Polen/enzimología , Polen/inmunología , Polisacárido Liasas/química , Polisacárido Liasas/aislamiento & purificación , Polisacárido Liasas/metabolismo , Pliegue de Proteína , Pruebas Cutáneas , TemperaturaRESUMEN
Mast cells (MCs) are central effector cells in allergic reactions that are often mediated by immunoglobulin E (IgE). Allergies commonly start at an early age, and both MCs and IgE are detectable in fetuses. However, the origin of fetal IgE and whether fetal MCs can degranulate in response to IgE-dependent activation are presently unknown. Here, we show that human and mouse fetal MCs phenotypically mature through pregnancy and can be sensitized by maternal IgE. IgE crossed the placenta, dependent on the fetal neonatal Fc receptor (FcRN), and sensitized fetal MCs for allergen-specific degranulation. Both passive and active prenatal sensitization conferred allergen sensitivity, resulting in postnatal skin and airway inflammation after the first allergen encounter. We report a role for MCs within the developing fetus and demonstrate that fetal MCs may contribute to antigen-specific vertical transmission of allergic disease.
Asunto(s)
Feto/inmunología , Hipersensibilidad/inmunología , Inmunoglobulina E/inmunología , Mastocitos/inmunología , Intercambio Materno-Fetal/inmunología , Alérgenos/inmunología , Ambrosia/inmunología , Animales , Degranulación de la Célula/inmunología , Femenino , Antígenos de Histocompatibilidad Clase I/fisiología , Humanos , Ratones , Ratones Endogámicos C57BL , Placenta/inmunología , Embarazo , Receptores Fc/fisiologíaRESUMEN
Background: Multiple immunoglobulin E (IgE) mediated sensitizations and/or allergies often coexist in patients with allergic rhinitis (AR). Several simultaneous allergen exposures in multiple IgE-mediated sensitizations and/or allergies may increase the allergen load and be related to disease severity. No study has verified whether positive allergen serum IgE levels and allergen categories together are associated with AR severity in adults. Objective: To investigate the effects of perennial dust mites (DMs) allergy and multiple serum sIgE-mediated autumn pollen allergy coexistence on symptom severity in adult patients with AR in autumn. Methods: In total, 153 patients with AR and with autumn pollen allergy (Artemisia argyi, ragweed, and hop) with or without DMs allergy were recruited in the autumn pollen season. Symptom severity was assessed by using the Chinese version of the visual analog scale (VAS): four rhinitis symptoms (sneezing, rhinorrhea, nasal pruritus, and nasal congestion) and two ocular symptoms (ocular itching and/or grittiness and/or redness, and ocular tearing) were scored at approximately the same period. We measured allergen serum sIgE levels for the inhaled allergens. The effects of DMs allergy and multiple autumn pollen allergy coexistence on symptom severity were analyzed. Results: Neither the sum of the autumn pollen allergens categories (total number of positive autumn pollen allergens, i.e., Artemisia argyi or ragweed or hop positive: 1; Artemisia argyi and ragweed positive: 2; Artemisia argyi, ragweed, and hop positive: 3) nor serum sIgE levels( total sIgE levels of positive autumn pollen allergens) exerted any influence on the severity of nasal and ocular symptoms (p > 0.05). When the concomitant DMs allergy status was considered, the sum of the positive autumn pollen allergen categories and accumulated positive autumn pollen and DMs serum sIgE levels (total levels of serum sIgE of positive autumn pollen allergens plus the levels of serum sIgE of DMs) had no influence on patients' symptom severity (p > 0.05). Conclusion: The coexistence of perennial DMs allergy and multiple autumn pollen allergy did not affect the severity of symptoms among adult patients with AR and with autumn pollen allergy in autumn.
Asunto(s)
Antígenos Dermatofagoides/inmunología , Antígenos de Plantas/inmunología , Hipersensibilidad/fisiopatología , Inmunoglobulina E/metabolismo , Polen/inmunología , Rinitis Alérgica Estacional/fisiopatología , Adolescente , Adulto , Ambrosia/inmunología , Animales , Artemisia/inmunología , Femenino , Humanos , Humulus/inmunología , Hipersensibilidad/complicaciones , Inmunización , Masculino , Persona de Mediana Edad , Pyroglyphidae/inmunología , Rinitis Alérgica Estacional/complicaciones , Estaciones del Año , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Ragweed frequently causes seasonal allergies in North America and Europe. In the United States, several related ragweed species with diverse geographical distribution cause allergic symptoms. Cross-reactivity towards related ragweed species of IgE and treatment-induced IgG4 has been demonstrated previously. However, less is known about the underlying T-cell cross-reactivity. METHODS: The allergen content of ragweed extracts was determined by mass spectrometry and related to T-cell epitopes of Amb a allergens (group 1, 3, 4, 5, 8 and 11) in 20 American ragweed allergic patients determined by FluoroSpot and proliferation assays. T-cell responses to 50 frequently recognized Amb a-derived T-cell epitopes and homologous peptides from western ragweed (Amb p), giant ragweed (Amb t) and mugwort (Art v) were investigated in an additional 11 American and 14 Slovakian ragweed allergic donors. RESULTS: Ragweed extracts contained all known allergens and isoallergens thereof. Donor T-cell responses were diverse and directed against all Amb a 1 isoallergens and to most minor allergens investigated. Similar response patterns were seen in American and Slovakia donors. Several epitopes were cross-reactive between isoallergens and ragweed species, some even including mugwort. T-cell cross-reactivity generally correlated with allergen sequence homology. CONCLUSION: T-cell epitopes of multiple allergens/isoallergens are involved in the diverse T-cell responses in ragweed allergic individuals. T-cell lines were highly cross-reactive to epitopes of related ragweed species without any apparent geographical response bias. These data support that different ragweed species can be considered an allergen homology group with Amb a as the representative species regarding diagnosis as well as allergy immunotherapy.
Asunto(s)
Alérgenos/inmunología , Ambrosia/inmunología , Epítopos de Linfocito T/inmunología , Hipersensibilidad Inmediata/inmunología , Linfocitos T/inmunología , Adulto , Reacciones Cruzadas , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: In contrast to the 3 major aeroallergens tree pollen, grass pollen, and house dust mites, allergic rhinitis caused by herbal pollen has received comparatively little attention in recent clinical studies. Since various weeds flower during summer until fall, allergic rhinitis to weeds may be underdiagnosed and/or mistakenly diagnosed as grass pollen allergy. OBJECTIVE: To investigate (i) the currently most frequent weed allergy between mugwort, ragweed, plantain, chamomile, nettle, and oilseed rape and (ii) time trends in prevalence of sensitization to weed pollen in the middle of Germany over the last 20 years. METHODS: This study, the largest of its kind to date, monocentrically evaluated the prick test results of a total of 6,220 patients with suspected RCA over a period of 20 years (1998-2017). RESULTS: In the study cohort, sensitization rates to plantain almost doubled from 26.6% in the decade 1998-2007 to 50.5% in 2008-2017. Identical increases were observed for ragweed, while sensitization rates for mugwort stayed largely unchanged. The most prominent increase in positive skin prick tests to plantain and ragweed pollen was mainly observed in younger patients. Further, we identified a trend toward polysensitization, currently dominated by plantain and ragweed. Sensitization to weed pollen was found to be highly associated with additional sensitizations to grass and/or birch pollen. CONCLUSION: Plantain is currently the best choice to screen rhinitis patients for weed allergy which identifies 86% of all weed-sensitized individuals, at least in Germany. Over the last 20 years, we demonstrate a significant rise in the total number of weed pollen sensitization as well as increases in polysensitization, predominantly in younger patients.
Asunto(s)
Alérgenos/inmunología , Ambrosia/inmunología , Plantago/inmunología , Polen/inmunología , Rinitis Alérgica/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Plantas/inmunología , Artemisia/inmunología , Niño , Preescolar , Femenino , Alemania , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Extractos Vegetales/inmunología , Prevalencia , Estudios Retrospectivos , Rinitis Alérgica Estacional/inmunología , Pruebas Cutáneas/métodos , Adulto JovenAsunto(s)
Alérgenos/inmunología , Ambrosia/inmunología , Hipersensibilidad/inmunología , Poaceae/inmunología , Antígenos de Plantas/inmunología , Susceptibilidad a Enfermedades , Humanos , Hipersensibilidad/diagnóstico , Polen/inmunología , Índice de Severidad de la Enfermedad , Evaluación de SíntomasRESUMEN
Pollen allergies are a major source of seasonal allergic rhinitis in North America. This type of rhinitis affects 17% of adults in Quebec, a marked increase in the last 30 years. Ragweed (Ambrosia artemisiifolia L.) pollens are responsible for 50% to 90% of rhinitis cases. Climate change has played a significant role in the increased prevalence of seasonal allergic rhinitis over the last few decades. In 2015, the Quebec government put in place a strategy to tackle this problem, the Stratégie québécoise de réduction de l'herbe à poux et des autres pollens allergènes [Quebec strategy to reduce ragweed and other allergenic pollens]. Based on solid evidence, the Strategy advocates for co-operation between stakeholders and the integration of control measures into the maintenance practices of municipalities and other large public and private landowners. This article presents the scientific data underpinning the Strategy and initial successes of the action taken under the Strategy.
Climate change increases the quantities and allergenic potential of ragweed pollen. Seasonal allergic rhinitis caused by these pollens has increased significantly in North America. Simple environmental control methods can clinically decrease the impact of ragweed pollen. A coordinated policy that incorporates these control measures in municipalities' groundskeeping practices is being implemented in Quebec.
Les changements climatiques augmentent les quantités et le potentiel allergène du pollen de l'herbe à poux (ambroisie). La rhinite allergique saisonnière liée à ces pollens est en augmentation marquée en Amérique du Nord. Des moyens de contrôle environnemental simples peuvent diminuer cliniquement l'impact du pollen de l'herbe à poux. Une politique concertée qui intègre des mesures de contrôle dans les pratiques d'entretien des terrains par les municipalités est en implantation au Québec.
Asunto(s)
Cambio Climático , Exposición a Riesgos Ambientales/efectos adversos , Salud Ambiental , Promoción de la Salud/organización & administración , Hipersensibilidad/etiología , Polen/efectos adversos , Ambrosia/efectos adversos , Ambrosia/inmunología , Canadá/epidemiología , Femenino , Humanos , Hipersensibilidad/epidemiología , Masculino , Polen/inmunología , Prevalencia , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Quebec , Rinitis Alérgica Estacional/epidemiología , Medición de RiesgoRESUMEN
BACKGROUND: Controlled allergen challenge facilities (CACF), in disparate geographic regions with dissimilar engineering and base populations, have historically functioned as single, independent sites in clinical allergy trials. We aimed to demonstrate "between-unit reproducibility" to allow controlled challenge trials of participants using 2 CACFs. OBJECTIVE: To compare and standardize 2 CACFs located in Kingston, Ontario, Canada, and San Antonio, Texas, by examining participant-reported symptom severity during qualifying and treatment visits and evaluating response to treatment, while using the same allergen. METHODS: At 2 different CACFs, participants were enrolled in a double-blind, placebo-controlled, crossover intervention trial with cetirizine 10 mg. Different distribution devices delivered common short ragweed pollen via laminar air flow and maintained an airborne concentration of 3500 ± 700 grains/m3 in both facilities. A 1-hour "sham" run with no pollen release preceded a priming exposure of 3 hours and was followed 3 days later by a qualifying/treatment 5-hour exposure. At least 14 days later, another priming exposure was followed by the crossover exposure and treatment. RESULTS: Forty-eight and 43 subjects completed the study at Kingston and San Antonio, respectively. Demographics were similar. Fewer than 10% exhibited symptoms with sham exposure. No significant differences were found between the 2 facilities in maximal total rhinoconjunctivitis symptom score, total nasal symptom score, and total ocular symptom score, nor in areas under the curve. In both facilities, no significant effects of cetirizine 10 mg over placebo were detected. CONCLUSION: The results were equivalent, demonstrating that the 2 CACFs can be used together in dual-center clinical trials and show the possibility of multicenter trials involving multiple CACFs.