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Summary: Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals".

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More than 10% of the world's population suffers from an immunoglobulin E (IgE)-mediated allergy to cats which is accompanied mainly by respiratory symptoms such as rhinitis and asthma. Several cat allergen molecules have been identified, but their allergenic activity has not been investigated in depth. Purified cat allergen molecules (Fel d 1, Fel d 2, Fel d 3, Fel d 4, Fel d 6, Fel d 7 and Fel d 8) were characterized via mass spectrometry and circular dichroism spectroscopy regarding their molecular mass and fold, respectively. Cat-allergen-specific IgE levels were quantified via ImmunoCAP measurements in IgE-sensitized subjects with (n = 37) and without (n = 20) respiratory symptoms related to cat exposure. The allergenic activity of the cat allergens was investigated by loading patients' IgE onto rat basophils expressing the human FcεRI receptor and studying the ability of different allergen concentrations to induce ß-hexosaminidase release. Purified and folded cat allergens with correct masses were obtained. Cat-allergen-specific IgE levels were much higher in patients with a respiratory allergy than in patients without a respiratory allergy. Fel d 1, Fel d 2, Fel d 4 and Fel d 7 bound the highest levels of specific IgE and already-induced basophil degranulation at hundred-fold-lower concentrations than the other allergens. Fel d 1, Fel d 4 and Fel d 7 were recognized by more than 65% of patients with a respiratory allergy, whereas Fel d 2 was recognized by only 30%. Therefore, in addition to the major cat allergen Fel d 1, Fel d 4 and Fel d 7 should also be considered to be important allergens for the diagnosis and specific immunotherapy of cat allergy.

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The major cat allergen Fel d 1 is a tetrameric glycoprotein from the secretoglobin superfamily. Fel d 1's biological role is unknown, but it has been previously shown that it participates in semiochemical binding/transportation. Fel d 1 has linear epitopes, but its conformational epitope sites remain unclear. In this study, we predicted the B-cell epitopes of Fel d 1 and explored semiochemical dynamics with epitopes using bioinformatics tools. The epitope residues were tabulated for chains 1 and 2 and the heterodimers of Fel d 1. The residual interactions of Fel d 1 with IgE were evaluated, and the prominent epitope sites were predicted. The molecular dynamics simulation (MDS) of Fel d 1 was performed with seven reported semiochemicals to evaluate the Fel d 1-ligand complex stability and decipher the semiochemical effect on Fel d 1 conformational epitopes. Fel d 1-lauric acid, Fel d 1-oleic acid, and Fel d 1-progesterone showed more stability and less fluctuation than other compounds. Fel d 1-linoleic acid and Fel d 1-pregnenolone displayed the most unstable complex with fluctuations. The effects of conformational changes on epitopes are discussed. All the ligand complexes drive substantial fluctuation towards the functionally exposed IgE-binding epitopes. Fel d 1 could be examined for its ligand-binding and conformational changes caused by mutations of B-cell epitopes.

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Exposure to biocontaminants, such as dust mites, animal dander, bacteria, and mold, is associated with a range of health effects. This study identified household characteristics associated with indoor biocontaminant loadings in four Canadian cities. Floor dust was collected in 290 Canadian homes in Edmonton, Halifax, Montreal, and Windsor. The dust samples were analyzed for house dust mite allergens (Der f 1 and Der p 1), cat allergen (Fel d 1), cockroach allergen (Bla g 1), beta-(1,3)-D-glucan, and endotoxin. Household information was obtained through questionnaires and home inspections. We performed univariate and multivariate analyses to identify household determinants of biocontaminant loadings and mold odor presence. We observed large regional variations for all biocontaminants, except for cockroach allergen. The ranges of the contaminants measured in loadings and concentrations were similar to that of previous Canadian studies. Household characteristics including presence of carpeting, low floor cleaning frequency, older home age, presence of pets, and indoor relative humidity above 45% were positively associated with the presence of multiple indoor biocontaminants. High floor cleaning frequency and use of dehumidifiers were negatively associated with the presence of multiple indoor biocontaminants. Mold odor was positively associated with older home age, past water damage, and visible mold growth.

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OBJECTIVE: The aim of the study was to find out whether allergen and endotoxin concentrations in offices differ from those measured at the homes of employees, and identify the parameters that influence exposure. METHODS: Electrostatic dust collectors (EDCs) were placed in five office buildings (68 rooms, 436 EDCs), as well as the homes of the office workers (145 rooms, 405 EDCs) for 14 days, four times a year. In addition, surface samples were collected from the offices four times a year by vacuuming the carpeted floors. Domestic mite (DM), and the major cat and dog allergens (Fel d 1 and Can f 1) were quantified in all samples using fluorescence enzyme immunoassays. Endotoxin was measured in the EDC samples, using the Limulus amoebocyte lysate assay. The allergen and endotoxin concentrations were log transformed and analysed with multilevel models. RESULTS: Endotoxin concentrations were significantly higher in personal homes compared to levels measured in the offices, and depended on the number of persons living in each household, as well as the presence of a dog. DM allergens were significantly higher in households than in offices, and were significantly higher in bedrooms compared to living rooms. Offices occupied by cat owners had significantly higher Fel d 1 concentrations than offices or homes without. Additionally, Can f 1 concentrations were significantly higher in offices occupied by dog owners compared to those without. CONCLUSIONS: Pet owners appear to transfer cat and dog allergens to their offices. Therefore, in case of allergy complaints at the office, employers and physicians might consider possible contamination by cat and dog allergens.

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Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) technology offers the unique potential for unequivocally deleting allergen genes at the source. Compared to prior gene editing approaches, CRISPR boasts substantial improvements in editing efficiency, throughput, and precision. CRISPR has demonstrated success in several clinical applications such as sickle cell disease and ß-thalassemia, and preliminary knockout studies of allergenic proteins using CRISPR editing show promise. Given the advantages of CRISPR, as well as specific DNA targets in the allergen genes, CRISPR gene editing is a viable approach for tackling allergy, which may lead to significant disease improvement. This review will highlight recent applications of CRISPR editing of allergens, particularly cat allergen Fel d 1, and will discuss the advantages and limitations of this approach compared to existing treatment options.

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PURPOSE OF REVIEW: The goal of this review is to compress all important information and results of the research in reducing cat allergen exposure using air filtration. Fel d 1 is the major allergen responsible for IgE responses in 90 to 95% of patients with cat allergy. RECENT FINDINGS: Reduction of cat allergen in indoor air with different air filtration systems and portable devices has been demonstrated in the majority of the studies. Recently, early and late asthmatic responses were significantly reduced using portable HEPA air cleaners in an environmental exposure chamber. This review provides a comprehensive overview of the current state of airborne Fel d 1 air filtration targeting the most efficient devices in cat allergen reduction. Novel emerging HEPA filters are targeting reduction of cat indoor asthma trigger so patient can might benefit from efficient solution.

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OBJECTIVES: Most studies on indoor allergen exposure used vacuumed surface samples for quantification. One alternative is electrostatic dust collectors (EDCs), which sample previously airborne settled dust. The aim of this study was to compare allergen quantification using two different sampling methods, with respect to repeatability, and to determine how well the results agree with one another. METHODS: Four times a year, measurements were made from samples that were either collected from the vacuuming of surfaces, or from EDCs, from 20 German day-care centers totaling 167 rooms. Overall, 504 vacuumed samples collected from smooth floors, 435 samples from carpets, 291 samples from upholstered furniture and beds, and 605 EDC samples were analyzed using six fluorescence enzyme immunoassays recognizing Fel d 1, Can f 1, Mus m 1, domestic mite (DM), Dermatophagoides pteronyssinus (Dp), and Tyrophagus putrescentiae (Tp) antigens. Variances and correlations among the repeat measurements over the course of the year within each sample type, and the correlations between surface samples and the corresponding EDC samples were calculated. RESULTS: Repeat measurements over the year correlated significantly with one another. However, only Fel d 1, Can f 1, and DM in the EDC samples; DM, Dp, Tp, and Fel d 1 in the upholstered furniture samples; and DM in the carpet samples show representative results of single measurements according to their variance ratios (within-room/between-room variance <1). The highest correlation between surface and EDC samples was found for Fel d 1 on the upholstered furniture (r 0.52), followed by Can f 1 on the upholstered furniture and Can f 1 on carpets (r 0.47 and 0.45, respectively). The maximum correlation for mite antigens was between carpet samples and EDC (DM r 0.27, Dp r 0.33). Mus m 1 and Tp antigens for the most part did not correlate to the EDC results. CONCLUSIONS: Both vacuumed dust from upholstered furniture and EDC samples were suitable for repeatable quantification of several allergens in day-care centers within a year. However, there was little agreement among the different collection methods, especially for Mus m 1 and certain mite antigens. Therefore, the method and location used for collection may greatly influence allergen exposure assessment and study results.

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This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa.

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BACKGROUND: Environmental control to reduce the amount of allergens in a living place is thought to be important to avoid sensitization to airborne allergens. However, efficacy of environmental control on inactivation of airborne allergens is not fully investigated. We have previously reported that positively- and negatively-charged plasma cluster ions (PC-ions) reduce the IgE-binding capacity of crude allergens from Japanese cedar pollen as important seasonal airborne allergens. Cat (Felis domesticus) and fungus (Aspergillus fumigatus) are also important sources of common airborne allergens in living spaces throughout the year, and early sensitization with those allergens is considered to be a risk factor for future development of allergic rhinitis, pollinosis and asthma. The aim of this study is to examine whether the PC-ions reduce the IgE-binding capacity of a cat major allergen (Fel d 1) and fungal allergens in an experimental condition. METHODS: Fel d 1, crude fungal extract, or a fungal major allergen Asp f 1, was treated with PC-ions for 6 h in an experimental cylindrical apparatus. Sham-treated allergens were prepared in the same experimental apparatus without generation of PC-ions. The degradation of the PC-ions-treated Fel d 1 was analyzed by SDS-PAGE, and the IgE-binding capacity of the PC-ions-treated allergens was analyzed by ELISA inhibition assay. RESULTS: Exposure of Fel d 1, crude fungal extract and Asp f 1 to PC-ions significantly decreased protein content of Fel d 1 or Asp f 1, respectively. SDS-PAGE analysis suggested that the decreased Fel d 1 content upon exposure with PC-ions was attributable to protein degradation. ELISA inhibition indicated that the PC-ions treatment significantly impaired IgE-binding capacities of Fel d 1, crude fungal allergens, and Asp f 1 compared to sham treatment. DISCUSSION: Our data suggest that treatment with PC-ions not only reduce indoor cat and fungal allergens, but also impair their allergenicity. CONCLUSION: These results suggest that environmental control with PC-ions is useful for inactivation of indoor cat and fungal allergens.

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Information on the antigenic repertoire, especially the IgE-binding epitopes of an allergen is important for understanding the allergen induced immune response and cross-reactivity, as well as for generating the hypoallergenic variants for specific component resolved immunotherapy/diagnosis (CRIT and CRD). Data on the IgE-binding epitopes of cat allergens are scarce. In this study, a novel IgE-binding epitope of the cat major allergen, Fel d 1, was identified. Mouse monoclonal antibody (MAb) specific to the Fel d 1 was produced. Computerized intermolecular docking was used for determining the residues of the Fel d 1 bound by the specific MAb. The presumptive surface exposed residues of the Fel d 1 intrigued by the MAb are located on the chain 1. They are: L34 and T37 (helix 1); T39 (between helices 1 and 2); P40, E42 and E45 (helix 2); R61, K64, N65 and D68 (helix 3); and E73 and K76 (helix 4). The MAb competed efficiently with the cat allergic patients' serum IgE for Fel d 1 binding in the competitive IgE binding assay, indicating allergenicity of the MAb epitope. The newly identified allergenic epitope of the Fel d 1 is useful in a design of the CRIT and CRD for cat allergy.

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Temperature-controlled laminar airflow improves symptoms in atopic asthmatics, but its effects on personal allergen exposure are unknown. We aimed to evaluate its effects on personal cat allergen and particulate exposures in a simulated bedroom environment. Five healthy volunteers lay under an active and an inactive temperature-controlled laminar airflow device for 175 min, in a simulated bedroom containing bedding from a cat owner. Total airborne particles (≥0.5 - ≥10 µm diameter) were quantified with a laser particle counter. Airborne allergen was sampled with Institute of Occupational Medicine filters. Inhaled exposure was sampled with nasal air samplers. Allergen-containing particles were quantified by immunoassay. Treatment reduced total airborne particles (>0.5 µm diameter) by >99% (P < 0.001) and reduced airborne allergen concentration within the breathing zone (ratio of median counts = 30, P = 0.043). Treatment reduced inhaled allergen (ratio of median counts = 7, P = 0.043). Treatment was not associated with a change in airborne allergen concentration outside of the breathing zone (P = 0.160). Temperature-controlled laminar airflow treatment of individuals in an allergen-rich experimental environment results in significant reductions in breathing zone allergenic and non-allergenic particle exposure, and in inhaled cat allergen exposure. These findings may explain the clinical benefits of temperature-controlled laminar airflow.

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PURPOSE: To investigate the prevalence rate of sensitization to indoor allergens, especially cat allergen in children with nasal symptoms in Kunpo city. METHODS: This study was a retrospective analysis of our radioallergosorbent test (RAST) database. We included 926 children with nasal symptoms between 3 months and 14 years of age. They underwent RAST which included 5 indoor and 4 food allergens. They were grouped according to age (0 to 3 years, 3 to 6 years, 6 to 9 years, 9 to 15 years). We calculated the prevalence rate of that sensitization according to age groups. RESULTS: Among the patients, 50.4% had the sensitization to at least > or =1 allergen of the RAST. The prevalence rate of sensitization increased according to the age group (P<0.05). The most common indoor allergen was Dermatophagoides farinae (D.f.) (22.6%), followed by cat (22.5%) and Dermatophagoides pteronyssinus (D.p.) (17.4%). Especially in the 0 to 3 age group, cat allergen (22.1%), was the predominant allergen, followed by dog (18.1%) and D.f. (8.7%). Among 926 patients, the rate of cat ownership was only 0.43%. The most common food allergen was pork (15.7%), followed by milk (4.9%) and egg white (3.2%). Pearsons test revealed significant correlation between cat and pork (r=0.563, P=0.000). CONCLUSION: This study shows a high rate of sensitization to cat allergen especially the 0 to 3 age group. It might be caused by exposure to wild cat in the community. We need to design a policy to reduce airborne cat allergen in the community.

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