Una plaga citadina peligrosa: los murciélagos / A dangerous urban pest: bats

Los murciélagos son mamíferos vertebrados presentes en la Ciudad de Buenos Aires, estimándose una población de 4 animales por habitante. Son portadores de varias enfermedades importantes y además empeoran las condiciones respiratorias de enfermos crónicos. En el campo cumplen una interesante función, ya que se alimentan de insectos perjudiciales para las siembras. El guano puede ser útil en el abono de la tierra debido al aporte de carbono y nitrógeno. En las ciudades su presencia tiene consecuencias diferentes. Se encuentran en los taparrollos de las habitaciones, así como también en todas las oquedades de muros, árboles, grietas, etc. Se exponen aquí los peligros y los cuidados que deben tenerse en la Ciudad de Buenos Aires ante la invasión de estos quirópteros. (AU)

Bats are vertebrate mammals present in the City of Buenos Aires, with an estimated population of 4 animals per inhabitant. They are carriers of several important diseases and also worsen the respiratory conditions of the chronically ill. In rural areas they fulfill an interesting function, since they feed on insects harmful to crops. Guano can be useful in soil fertilization due to its contribution of carbon and nitrogen. In cities their presence has different consequences. They are found in the roll covers of the rooms as well as in all the hollows of walls, trees, cracks, etc. The dangers and precautions to be taken in the city of Buenos Aires in the face of the invasion of these chiroptera are described here. (AU)

Specific gut microbiome signatures and the associated pro-inflamatory functions are linked to pediatric allergy and acquisition of immune tolerance.

Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.

Cross-reactivity of Can f 1 with Syrian hamster and Fel d 1 in children

Introduction and objectives: With increasing pet allergies among pediatric patients, the need for precise environmental care is increasing. We investigated the clinical, immunological, and environmental characteristics of pediatric patients sensitized to a dog to evaluate the cross-antigenicity of canine lipocalin Can f 1 with feline lipocalin Fel d 1 and Syrian hamster extract. Materials and methods: The protein fractions of the processed and commercial Syrian hamster extracts were compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). An enzyme-linked immunosorbent assay (ELISA) inhibition test was performed on Can f 1, Fel d 1, and processed Syrian hamster extract, and the antigen-specific immunoglobulin E (IgE)-binding capacity for each antigen was analyzed using serum samples from patients. Results: Twelve of 19 patients with a median age of 40.5 months were symptomatic when exposed to dogs. Eleven (91.7%) patients showed a positive IgE response to Can f 1. Two patients were positive for Fel d 1-specific IgE antibody, and one was positive for hamster-specific IgE antibody. SDS-PAGE confirmed the presence of different patterns of protein bands between the commercial and processed hamster extracts. There was no cross-antigenicity among Can f 1, Fel d 1, and processed Syrian hamster extract. Conclusions: Since the standard commercial hamster extract did not contain Syrian hamster antigens that were diverse enough, caution should be taken when using it. In children allergic to cats and dogs, sensitization to isolated Can f 1 or Fel d 1 is unlikely to cause cross-reactivity to Syrian hamster hair and epithelium (AU)

Establishment of Rat Models of Different Pathological Types of Hypersensitivity Pneumonitis Using Pigeon Droppings.

BACKGROUND: The pathogenesis and pulmonary histopathological characteristics of hypersensitivity pneumonitis (HP) are not yet fully understood. Therefore, we established animal models of HP of different stages, aiming to provide support for research on this disease. METHODS: We established rat models of pigeon breeder's lung of different pathological types by creating freeze-dried allergen powder from fresh pigeon feathers, dander, and other droppings. Freeze-dried allergen powder suspensions of pigeon droppings were used to establish 2 rat models of HP, one by aerosol inhalation and one by airway instillation, and the rats were sacrificed after different lengths of time to observe the pathological changes in their lung tissues. RESULTS: By the 40th week after allergen inhalation, granulomas were the main changes in the model, without fibrotic changes. When using airway instillation to establish the model, at the 20th week, group 1 (low dose + twice/week) and group 2 (medium dose + twice/week) showed granuloma changes, but no fibrosis; group 3 (high dose + once/week) and group 4 (high dose + twice/week) both showed obvious pulmonary fibrotic changes, but the death rate of rats in group 4 was greater. CONCLUSIONS: Both aerosol inhalation and airway instillation of freeze-dried pigeon allergen powder can successfully establish an HP model. The airway instillation method can cause pulmonary fibrotic changes in a short time, and the pulmonary pathological changes of animal models manifest with an obvious time-dose effect.

Component-resolved diagnosis using guinea-pig allergens elucidates allergen sensitization profiles in allergy to furry animals.

BACKGROUND: Furry animals are an important source of indoor allergens. Diagnosis of allergy to small pets such as guinea-pigs still relies on animal dander extracts which do not allow to define the primary sensitization source. OBJECTIVE: To identify major guinea-pig allergens and to evaluate their potential as marker allergens for in vitro IgE-diagnosis in comparison with dander extracts. METHODS: A group of patients allergic to guinea-pig (n = 29) and a group of patients allergic to cat and dog (n = 30) were recruited for the study. A panel of four guinea-pig lipocalin allergens was expressed as recombinant proteins in E. coli. Specific IgE were quantified by ImmunoCAP and ELISA. RESULTS: The combination of 4 guinea-pig lipocalin allergens, including 2 new lipocalins, Cav p 1.0201 and Cav p 6.0101, and the previously characterized lipocalins Cav p 2 and Cav p 3, enabled the identification of 90% of all patients allergic to guinea-pig. The vast majority had specific IgE to Cav p 1 (83%). Cav p 6 shares 54% sequence identity with Fel d 4 and Can f 6 and was found to be IgE-cross-reactive with these allergens. In the group of cat- and dog-allergic patients, 73% had also specific IgE to guinea-pig dander. However, only 27% of the cat /dog-allergic patients had specific IgE to any of the non-cross-reactive guinea-pig allergens Cav p 1, Cav p 2 or Cav p 3. The high prevalence of IgE to guinea-pig dander could be explained by IgE-cross-reactivity among serum albumins and certain lipocalins. CONCLUSIONS AND CLINICAL RELEVANCE: The availability of specific allergen markers is essential for the assessment of primary sensitization, especially in polysensitized patients. The proposed panel of guinea-pig allergens Cav p 1, Cav p 2 and Cav p 3 is a first step to component-resolved IgE-diagnosis of allergy to small furry pets.

Childhood asthma: Novel endotyping by cytokines, validated through sensitization profiles and clinical characteristics.

BACKGROUND: Specific allergy sensitization pattern, using "component-resolved diagnosis" (CRD), is a central component of allergy and asthma in childhood. Besides this, allergic asthma has been characterized by a Th2-shifted endotype with elevation of classical Th2 cytokines. Recently, other endotypes with distinct mechanisms focusing on cytokine regulation evolved, yet those pathways are still not well understood. OBJECTIVE: (a) To define reproducible immunological endotypes using cytokine expression in an asthma cohort and (b) to characterize their sensitization profile and clinical phenotype. METHODS: Supernatants from PBMCs of 234 children (median age 10 years) of an asthma cohort were analysed for cytokine expressions. The children were split into a training (n = 49) and validation (n = 185) group. The training group was used to identify immunological endotypes by clustering cytokine expressions, which were then assessed regarding clinical characteristics and specific IgE of recombinant allergen components. Next, our findings were validated in the validation group. RESULTS: We identified novel endotypes based on primarily unstimulated cytokine expression. One endotype showed an IFN-γ/Interleukin (IL)-17/IL-5 predominance, a different sensitization pattern (high in birch/apple; p < .01), and inferior lung function (p < .01). A second endotype grouped young children with food allergy and reduced lung function. Our findings were reproducible in the validation group. CONCLUSION AND CLINICAL RELEVANCE: We identified two novel clinical asthma endotypes via cytokine expression pattern with distinct sensitization patterns. These novel findings are critical for clinical guidance and open avenues for identifying underlying mechanisms and more patient-specific therapies.

Component-resolved diagnostics in pet allergy: Current perspectives and future directions.

Furry mammals kept as pets are important allergen sources. The prevalence of sensitization to dander from various animals appears to be increasing worldwide. Several mammalian allergens from diverse species and distinct protein families have been characterized, and some are available for component-resolved diagnostics (CRD). This review presents an overview of mammalian aeroallergens, with a focus on cat, dog, and horse allergens. The potential of CRD in fine-tuning the diagnostic workup following traditional methods based on whole- allergen extracts and allergen immunotherapy is discussed. The review highlights the clinical utility of CRD, particularly as a marker/predictor of increased asthma risk and disease severity. Finally, several perspectives of the future implications of CRD are offered in the context of furry animal allergens.

Fungal sensitization and positive fungal culture from sputum in children with asthma are associated with reduced lung function and acute asthma attacks respectively.

BACKGROUND: Sensitization to thermotolerant fungi, including filamentous fungi and Candida albicans, is associated with poor lung function in adults with severe asthma. Data in children are lacking. Environmental exposure to fungi is linked with acute severe asthma attacks, but there are few studies reporting the presence of fungi in the airways during asthma attacks. METHODS: We investigated the association between fungal sensitization and/or positive fungal sputum culture and markers of asthma severity in children with chronic and acute asthma. Sensitization was determined using serum-specific IgE and skin prick testing against a panel of five fungi. Fungal culture was focused towards detection of filamentous fungi from sputum samples. RESULTS: We obtained sensitization data and/or sputum from 175 children: 99 with chronic asthma, 39 with acute asthma and 37 controls. 34.1% of children with chronic asthma were sensitized to thermotolerant fungi compared with no children without asthma (p =< 0.001). These children had worse pre-bronchodilator lung function compared with asthmatics without sensitization including a lower FEV1 /FVC ratio (p < .05). The isolation rate of filamentous fungi from sputum was higher in children with acute compared with chronic asthma. CONCLUSIONS: Fungal sensitization is a feature of children with chronic asthma. Children sensitized to thermotolerant fungi have worse lung function, require more courses of systemic corticosteroids and have greater limitation of activities due to asthma. Asthma attacks in children were associated with the presence of filamentous fungi positive sputum culture. Mechanistic studies are required to establish whether fungi contribute directly to the development of acute asthma.

Immunogenicity of a new allergoid from Felis domesticus.

BACKGROUND: The chemical modification of allergens with glutaraldehyde improves safety while maintaining clinical efficacy, which permits the administration of higher doses of immunotherapy, reducing the risk of adverse reactions. The aim of this study is to evaluate the immunogenic capacity of a new cat dander polymer by immunizing mice and quantifying immunoglobulins in serum, in comparison with the non-modified allergen. METHODS: The study consists of the immunization of three mice groups with the polymerized and the native extract, together with a negative control group. The immunoglobulin levels in serum have been measured by indirect ELISA. By means of the non-parametric Mann-Whitney U test, it was determined if there were significant differences in the values of specific antibodies between groups. RESULTS: The group immunized with the allergoid showed significantly higher specific IgG and IgG1 values to dander allergens and specific IgG to the major allergen Fel d 1, while there were no significant changes in IgG2a and IgE values. These results could be due to a higher immunization dose. The vaccine formulation was based on the optimal defined dose for clinical efficacy of allergen immunotherapy. CONCLUSIONS: This preclinical study carried out with the present assay has established that the allergoid of cat dander extract, as designed for its optimal use in allergen immunotherapy, produces a higher specific IgG than the native extract, in addition to showing significantly higher specific IgG1 levels, evidencing a greater effectiveness in immunization.

Allergen-specific immunotherapy for patients with atopic dermatitis sensitized to animal dander.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease, and AD patients are commonly sensitized to house dust mite (HDM). Of the several treatment options available, allergen-specific immunotherapy (AIT) has been recognized as an effective treatment modality that is directed toward the immunoglobulin E (IgE)-mediated nature of AD, and subcutaneous administration using HDM is most commonly used for AIT in AD. For patients sensitized to animal (dog or cat) dander, the treatment may not be easy, especially when avoiding the allergen is not possible. METHODS: This study enrolled patients with AD who were sensitized to cat and/or dog dander and underwent AIT (n = 19). Patients' medical information was obtained, including past treatment history, treatment duration of AIT, and the progress of treatment. Also, the specific IgE levels and IgG4 levels were measured before and after AIT. RESULTS: A total of 19 patients with AD underwent AIT using cat and/or dog dander. The patients consisted of 4 males and 15 females with an average age of 31.74 ± 9.71. Only two patients had AD only, and the other 17 patients had one or more concomitant allergic diseases, such as allergic rhinitis, allergic asthma, or allergic conjunctivitis. Seven patients were not sensitized to HDMs and only sensitized to cat and/or dog dander. The duration of AIT ranged from 2 to 58 months. The symptoms of 17 patients were well-controlled, requiring only topical treatment and/or oral antihistamines. One patient required systemic cyclosporine, but only of low dose (25 mg/day). The specific IgE levels were decreased (P = .005) and IgG4 levels showed the tendency of increasing after AIT. No adverse events were observed in these patients. CONCLUSION: Although a larger number of patients for a longer follow-up period are needed to precisely assess the treatment efficacy, AIT using cat and/or dog dander may be an effective treatment option for AD patients, especially for severe AD patients with other respiratory allergic comorbidities who cannot completely avoid the exposure to animal dander.

The Toxicological Intersection between Allergen and Toxin: A Structural Comparison of the Cat Dander Allergenic Protein Fel d1 and the Slow Loris Brachial Gland Secretion Protein.

Slow lorises are enigmatic animal that represent the only venomous primate lineage. Their defensive secretions have received little attention. In this study we determined the full length sequence of the protein secreted by their unique brachial glands. The full length sequences displayed homology to the main allergenic protein present in cat dander. We thus compared the molecular features of the slow loris brachial gland protein and the cat dander allergen protein, showing remarkable similarities between them. Thus we postulate that allergenic proteins play a role in the slow loris defensive arsenal. These results shed light on these neglected, novel animals.

Nasal Provocation Test with Cat and Dog Extracts: Results according to Molecular Components.

BACKGROUND: IgE sensitization (atopy) to pets is commonly evaluated using pet dander extracts. However, the diagnosis by components seems to be more adequate to evaluate the clinical relevance (allergy) of sIgE sensitization. OBJECTIVE: To study the association between IgE sensitization to pet allergen components and clinical symptoms. Methodology. Dander extracts and sIgE levels to pet components (Can f 1, Can f 2, Can f 3, Can f 5, Fel d 1, Fel 2, and Fel 4) were measured in a rhinitis group (n = 101) and a control group (n = 101) and a control group (. RESULTS: Dog (34.6% vs. 23.5%) and cat dander (26.7% vs. 8.8%, p = 0.05) IgE sensitization was frequent among rhinitis and no-rhinitis subjects, and it was similar to dog (29.7% vs. 20.5%) and cat (18.8% vs. 8.8%) components. Polysensitization for dog (3.1, 95% CI: 1.5 to 6.1, p = 0.05) IgE sensitization was frequent among rhinitis and no-rhinitis subjects, and it was similar to dog (29.7% vs. 20.5%) and cat (18.8% vs. 8.8%) components. Polysensitization for dog (3.1, 95% CI: 1.5 to 6.1, p = 0.05) IgE sensitization was frequent among rhinitis and no-rhinitis subjects, and it was similar to dog (29.7% vs. 20.5%) and cat (18.8% vs. 8.8%) components. Polysensitization for dog (3.1, 95% CI: 1.5 to 6.1. CONCLUSIONS: Sensitization to pet dander extract identifies atopic patients, but its utility to predict clinical relevance is poor. Allergenic components could help to define the clinical relevance of sensitization to furry animals and could reduce the need for provocation test.

Subcutaneous immunotherapy with high-dose cat and dog extracts: a real-life study

BACKGROUND: Data on the efficacy of immunotherapy administered to patients with cat or dog allergy are scarce. OBJECTIVE: We aimed to evaluate the safety and efficacy of subcutaneous immunotherapy (SCIT) in patients with allergy to cat and dog dander. METHODS: Consecutive patients with rhinitis and/or asthma related to sensitization to cat or dog dander were included in a pragmatic, real-life, prospective, observational study. All patients had specific IgE to cat, dog, or both. SCIT was administered using an infusion pump over 3 sessions as part of a rush protocol, followed by monthly administration over 12 months. We recorded adverse events, clinical outcomes, pulmonary function, FeNO, symptoms of rhinitis and asthma, quality of life (QoL), Asthma Control Test (ACT) score, and visual analog scale (VAS) score at baseline, 6 months, and 12 months. RESULTS: The study population comprised 66 patients (38 females, 46 allergic to cat and 20 to dog), with ages ranging from 9 to 59 years. During the up-dosing phase, in which the infusion pump was used, 8.1% of doses elicited a systemic reaction and 5.4% caused a local reaction, while 9.3% of doses administered during the maintenance phase (ie, without an infusion pump) induced a systemic reaction. No local reactions were recorded. A significant improvement in FEV1, symptoms of rhinitis and asthma, QoL, use of medication, VAS score, and ACT score was observed at 6 months and continued at 12 months. Clinical improvement with cat extract was significantly better than with dog extract. CONCLUSIONS: High-dose SCIT has substantial clinical value in many cat- and dog-allergic patients

ANTECEDENTES: Hay pocos estudios sobre la eficacia de la inmunoterapia administrada a pacientes con alergia a perro o gato. OBJETIVO: Evaluar la seguridad y la eficacia de la inmunoterapia subcutánea (SCIT) en pacientes con alergia a estos dos animales. MÉTODOS: Se incluyeron pacientes consecutivos con rinitis y/o asma relacionados con la sensibilización al gato o al perro en un estudio observacional prospectivo, pragmático, en vida real. Todos los pacientes tenían IgE específica para gato y/o perro. La SCIT se administró utilizando una bomba de infusión (IP), en 3 sesiones como parte de un protocolo rápido, seguido de la administración mensual durante 12 meses. Se recopilaron datos sobre efectos adversos y resultados clínicos, función pulmonar, FeNO, síntomas de rinitis y asma, calidad de vida (QoL), prueba de control del asma (ACT) y escala analógica visual (VAS) al inicio, a los 6 y 12 meses. RESULTADOS: Se incluyeron 76 pacientes: 38 mujeres, 46 alérgicos a gato y 20 a perro, con edades comprendidas entre los 9 y los 59 años. Durante la fase de administración ascendente, utilizando una IP, el 8,1% de las dosis provocó una reacción sistémica (SR) y el 5,4% causó una reacción local (LR), mientras que el 9,3% de las dosis administradas durante la fase de mantenimiento (es decir, sin IP) desarrolló una SR, y no se registraron LRs. Se observó una mejoría significativa en el FEV1, en los síntomas de rinitis, de asma y en los cuestionarios de la calidad de vida, uso de medicación, VAS y ACT a los 6 meses y continuó a los 12 meses. La mejoría clínica con el extracto de gato fue significativamente mayor que con el perro. CONCLUSIONES: Las dosis altas de SCIT tienen un valor clínico sustancial en muchos pacientes alérgicos a perros y gatos

Heterogeneity of allergen content in male dog urine and dander

No disponible

Perceived Versus Actual Aeroallergen Sensitization in Urban Children.

BACKGROUND: Individuals often report allergy to specific aeroallergens, but allergy testing can reveal disparate sensitization. OBJECTIVE: To characterize the agreement between perceived and actual sensitization to individual aeroallergens in an urban pediatric population. METHODS: A total of 253 children were enrolled from pediatric clinics in New York, NY. Detailed questionnaires regarding perceived sensitization and serum specific IgE measurements to 10 common aeroallergens were completed. Agreement between perceived and actual sensitization (sIgE ≥ 0.35 kUA/L) to individual aeroallergens was assessed by Cohen's kappa. Multivariable logistic regression models adjusted for potential confounders were used to test for associations between perceived and actual sensitization. RESULTS: A total of 161 (63.6%) of 253 children reported perceived sensitization to 1 or more aeroallergen, and 203 (80.2%) were actually sensitized to 1 or more aeroallergen. Agreement between perceived and actual aeroallergen sensitization was fair for most aeroallergens, with greatest agreement for cat dander (κ, 0.42; 95% CI, 0.32-0.53) and dust (κ, 0.32; 95% CI, 0.20-0.44). Models adjusted for potential confounders showed nearly 6-fold odds of sensitization to cat dander given perceived cat allergy (adjusted odds ratio, 5.82; 95% CI, 2.91-11.64), and over 2-fold odds of sensitization to Dermatophagoides pteronyssinus, Dermatophagoides farinae, dog dander, or grass pollen given perceived sensitization to their respective allergens. Among children with no perceived sensitization, actual sensitization ranged from 5.4% to 30.4%, and was more common for indoor versus outdoor allergens, including cockroach. CONCLUSIONS: Children who perceive allergen sensitization to cat, dog, dust, or grass are likely to demonstrate actual sensitization to these individual allergens. Children with no perceived sensitization to allergens are nonetheless frequently sensitized.

Geographic and demographic variations of inhalant allergen sensitization in Koreans and non-Koreans.

BACKGROUND: To diagnose and treat respiratory allergic diseases, it is important to identify the specific allergens involved. Many differences exist between common inhalant allergens depending on the residential environment and demographic factors. This study aimed to compare common inhalant allergens between Koreans and non-Koreans according to their residential region, age, and sex. METHODS: This study evaluated 15,334 individuals who underwent serum tests for multiple allergen-specific immunoglobulin E at a tertiary academic medical center between January 2010 and December 2016. The individuals included 14,786 Koreans and 548 non-Koreans. The AdvanSure™ Allostation assay (LG Life Science, Korea) was used to test for 33 inhalant allergens. RESULTS: The house dust mite (HDM) was the most common allergen in both Koreans and non-Koreans, although the proportion of individuals with HDM sensitization was greater among Koreans. High sensitization rates for various pollen types were detected among Koreans in Gangwon region, whereas Japanese cedar pollen was unique among Koreans in Jeju region. Grass pollen and animal dander were relatively common among individuals from the Americas, whereas weed and grass pollen accounted for the 10 most common allergens for individuals from Central Asia. The total sensitization rate, sensitization to HDM, and sensitization to animal dander peaked among adolescents and young adults, then subsequently decreased with age. CONCLUSIONS: This large-scale study demonstrates that various regional and age-related differences exist in the allergen sensitization rates of Koreans and non-Koreans. These data could be useful for development of avoidance measures, immunotherapy for causative allergens, and policymaking regarding allergic diseases.

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling.

BACKGROUND: Frequent exacerbations of allergic asthma lead to airway remodeling and a decrease in pulmonary function, producing morbidity. Cat dander is an aeroallergen associated with asthma risk. OBJECTIVE: We sought to elucidate the mechanism of cat dander-induced inflammation-remodeling. METHODS: We identified remodeling in mucosal samples from allergic asthma by using quantitative RT-PCR. We developed a model of aeroallergen-induced experimental asthma using repetitive cat dander extract exposure. We measured airway inflammation using immunofluorescence, leukocyte recruitment, and quantitative RT-PCR. Airway remodeling was measured by using histology, collagen content, myofibroblast numbers, and selected reaction monitoring. Inducible nuclear factor κB (NF-κB)-BRD4 interaction was measured by using a proximity ligation assay in situ. RESULTS: Enhanced mesenchymal signatures are observed in bronchial biopsy specimens from patients with allergic asthma. Cat dander induces innate inflammation through NF-κB signaling, followed by production of a profibrogenic mesenchymal transition in primary human small airway epithelial cells. The IκB kinase-NF-κB signaling pathway is required for mucosal inflammation-coupled airway remodeling and myofibroblast expansion in the mouse model of aeroallergen exposure. Cat dander induces NF-κB/RelA to complex with and activate BRD4, resulting in modifying the chromatin environment of inflammatory and fibrogenic genes through its atypical histone acetyltransferase activity. A novel small-molecule BRD4 inhibitor (ZL0454) disrupts BRD4 binding to the NF-κB-RNA polymerase II complex and inhibits its histone acetyltransferase activity. ZL0454 prevents epithelial mesenchymal transition, myofibroblast expansion, IgE sensitization, and fibrosis in airways of naive mice exposed to cat dander. CONCLUSIONS: NF-κB-inducible BRD4 activity mediates cat dander-induced inflammation and remodeling. Therapeutic modulation of the NF-κB-BRD4 pathway affects allergen-induced inflammation, epithelial cell-state changes, extracellular matrix production, and expansion of the subepithelial myofibroblast population.

Development and characterization of an allergoid of cat dander for immunotherapy

BACKGROUND: Allergy to cats is a frequent cause of sensitization to indoor allergens and currently there are few alternatives to specific immunotherapy with cat native extracts. The objective is to develop and characterize a new allergoid to increase the tools available for use in clinical practice. METHODS: The allergoid cat dander extract (ACD) was developed from a native cat dander extract (NCD) by modification with glutaraldehyde, and the optimal process control was determined by SDS-PAGE, DOT BLOT and determination of free amine groups. The ACD was characterized in protein profile by SDS-PAGE, size exclusion chromatography (SEC) and peptide footprint. The allergenic profile of ACD was determined by immunoblot, IgE CAP inhibition and IgG competition ELISA. The major allergen content in NCD was obtained by the ELISA sandwich protocol and was extrapolated to ACD. RESULTS: The control process determined the optimal development of the allergoid. The ACD obtained contains 182.28μ g/mg of protein and 11.90 mig/mg of Fel d 1. SDS-PAGE and SEC confirmed the presence of high molecular weight proteins in ACD, and the peptide footprint showed the presence of Fel d 1 and Fel d 7. The high degree of polymerization was evidenced with the determination of the reduction of lysine residues in the allergoid, resulting 91.96%. The ACD showed a significant loss of allergenicity respect to NCD, while the IgG-binding capacity was maintained. CONCLUSIONS: The ACD obtained presents a good safety profile, so would be a good alternative for treatment of cat allergy

No disponible

Molecular allergy diagnostics refine characterization of children sensitized to dog dander.

BACKGROUND: Sensitization to dog dander is an important risk factor for rhinoconjunctivitis and asthma but is not sufficient for diagnosing dog allergy. Molecular allergy diagnostics offer new opportunities for refined characterization. OBJECTIVES: We sought to study the association between sensitization to all presently known dog allergen components and clinical symptoms of dog allergy in children evaluated by using nasal provocation tests (NPTs). METHODS: Sixty children (age, 10-18 years) sensitized to dog dander extract underwent NPTs with dog dander extract. Measurement of IgE levels to dog dander and to Can f 1, Can f 2, Can f 3, and Can f 5 was performed with ImmunoCAP, and measurement of IgE levels to Can f 4 and Can f 6 was performed with streptavidin ImmunoCAP. An IgE level of 0.1 kUA/L or greater was considered positive. RESULTS: There was an association between sensitization to an increasing number of dog allergen components and a positive nasal challenge result (P = .01). Sensitization to lipocalins (odds ratio [OR], 6.0; 95% CI, 1.04-34.5), in particular Can f 4 (OR, 6.80; 95% CI 1.84-25.2) and Can f 6 (OR, 5.69; 95% CI, 1.59-20.8), was associated with a positive NPT result. Monosensitization to Can f 5 was related to a negative NPT result (OR, 5.78; 95% CI, 1.01-33.0). CONCLUSION: Sensitization to an increasing number of dog allergen components and to lipocalins is associated with dog allergy. Monosensitization to Can f 5 should not be regarded primarily as a marker for dog allergy.