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Dog allergens are a common cause of allergic sensitisation and trigger respiratory symptoms worldwide. However, clinical evidence regarding dog immunotherapy is limited. Therefore, the aim of this study was to analyse the immunomodulatory properties of a new allergoid from dog dander, thereby deepening the understanding of the molecular mechanisms involved in the reestablishment of the tolerogenic response. Three independent batches of dog dander native and allergoid allergen extracts were manufactured and characterised. Allergenic profiles were analysed by the identification of all dog allergens and quantification of the major allergens Can f 1 and Can f 5. The allergenicity profile of the allergoid was studied using biological potency and basophil activation tests. In vitro immunomodulatory parameters was evaluated as the capacity of the allergoid to induce IgG antibodies that block IgE binding to the allergen and cytokine promotion (IFN-γ, IL-4, IL-6, IL-10, IL-13, and TNF-α) in PBMCs from allergic donors. The presence of all dog allergens, including Can f 1 and Can f 5, was confirmed in both types of extracts. The new allergoid showed a low IgE binding capacity, which significantly affected the activation of effector cells, such as basophils. The IgG antibodies induced by the allergoid in rabbits blocked human IgE binding epitopes on the dog native extract and induced Th1 and Treg responses by increasing IFN-γ and IL-10 levels in PBMCs from allergic donors. This new dog dander allergoid containing Can f 1 and Can f 5 showed a low capacity to bind IgE and to activate basophils in dog allergic patients. Furthermore, it showed potent activation of Th1 mediators and induction of tolerance through Treg activation. This allergoid could offer a safer profile than the native extract and could be an effective immunotherapy treatment for dog allergic patients. • The allergen profile and in vitro safety of a new dog dander allergoid is assessed. • The dog dander allergoid modulates the allergic response by inducing the secretion of regulatory cytokines. • This allergoid could be an effective immunotherapy treatment for dog allergic patients. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous immunotherapy is an effective allergy treatment only if properly dosed. In this article we review the data on the probable effective dose range for subcutaneous immunotherapy and convert the recommended doses into a clinically relevant format. Methods: A comprehensive literature search of dose‐response subcutaneous immunotherapy studies was done of EBM databases, Medline database, PreMedline, and the National Guideline Clearinghouse for the period 1980–2016. Recommended doses were converted to the volume of allergen extract that should be added to a 5‐mL maintenance vial. Results: A safe and effective dose for subcutaneous immunotherapy is likely 5–20 μg of major allergen per injection. A 0.5‐mL injection from a 5‐mL maintenance vial containing 0.2 mL of manufacturer's extract of each allergen should reach the lower end of the probable effective dose range for most allergens. A larger volume of extract is required to reach that range when treatment includes cat, dog, or only 1 dust mite. Increasing beyond the commonly prescribed 0.2 mL of manufacturer's extract added to a 5‐mL treatment vial is reasonable for nearly all allergens to achieve a maintenance dose higher in the probable effective dose range. Conclusion: Current otolaryngic allergy practice usually escalates patients to 0.5‐mL injections from 5‐mL maintenance vials containing 0.2 mL of manufacturer's extract of each allergen. With the main exceptions of cat and dog, those injections administered 1 or 2 times per month likely provide an efficacious dose of allergen and are consistent with published guidelines. A larger volume of extract should be considered in certain clinical situations. [ABSTRACT FROM AUTHOR]

Highlights: [•] The second three-dimensional structure of a dog allergen may be useful for developing specific immunotherapy against dog allergy. [•] As the ligand-binding site is different from that of another dog allergen, Can f 2, that suggests for its different biological function. [•] Dog allergen Can f 4 forms a similar dimeric structure as the horse lipocalin allergen Equ c 1. [•] Native mass spectrometry also shows dimerization for Can f 4 in solution. [•] Transient dimerization is probably an important feature of Can f 4 because oligomeric allergens can effectively present multiple identical epitopes. [Copyright &y& Elsevier]

Background Allergy to the domestic dog ( C anis familiaris) affects 5-10% of the population in affluent countries. Three of four patients are allergic to more than one pet, which can only partially be explained by cross-reactivity between serum albumins. The lipocalin protein family harbours allergens in mammalian species. Methods We set out to clone and characterize a novel dog allergen, and investigate its potential role in cross-sensitization between dog, cat and horse. The gene encoding Can f 6 was amplified from dog skin and bladder cDNA libraries. The corresponding allergen was produced and purified by recombinant techniques and evaluated by SDS-PAGE, size exclusion chromatography, circular dichroism spectra, ELISA and basophil activation test. Results Ig E antibodies to Can f 6 were found in serum from 38% of dog-sensitized subjects. Sequence similarities between the lipocalin allergens Can f 6, Fel d 4 (cat) and Equ c 1 (horse) suggested a probability for cross-reactivity, which was demonstrated by competitive ELISA. The biological relevance of Can f 6 was confirmed by basophil activation test in dog-allergic patients. Conclusion Can f 6 is a new lipocalin dog allergen that cross-reacts with lipocalins from horse and cat. Can f 6 and homologous allergens may contribute to multisensitization and symptoms in individuals allergic to mammals. [ABSTRACT FROM AUTHOR]

Background Dog dander is an important cause of respiratory allergy but its content of allergenic components is still incompletely known. While Can f 1, 2, 3 and 5 have been studied in detail, only fragmentary information is available on the lipocalin Can f 4. Objective To purify, clone and characterize dog dander allergen Can f 4. Methods Can f 4 was purified from dog dander extract by size exclusion, ion exchange and reverse phase chromatography. A cDNA encoding Can f 4 was cloned and used to produce recombinant Can f 4 in Escherichia coli. A 23 kDa protein from cow dander, displaying cross-reactivity with Can f 4, was purified and identified by amino acid sequencing and mass spectrometry. IgE antibody binding to dog and cow dander extract and to individual dog allergens among 37 dog allergic subjects and 44 pollen allergic controls was studied using ImmunoCAP. Results A dog genome segment containing the Can f 4 gene was bioinformatically identified and enabled the cloning of Can f 4 cDNA. Recombinant Can f 4 displayed close immunological and biochemical similarity to purified natural Can f 4 and bound IgE antibodies from 13/37 (35%) sera of dog allergic subjects. Can f 4 reactive sera showed IgE binding to a 23 kDa protein present in cow dander extract, related to a family of odorant-binding proteins. The dog and cow proteins shared 37% sequence identity and their cross-reactivity was demonstrated by IgE inhibition experiments. Conclusion Recombinant Can f 4 brings the panel of available dog allergens closer to completion and will be important in component-resolved diagnostics in allergy to animal epithelial allergens. Cite this as: L. Mattsson, T. Lundgren, P. Olsson, M. Sundberg and J. Lidholm, Clinical & Experimental Allergy, 2010 (40) 1276–1287. [ABSTRACT FROM AUTHOR]

Background: Dog dander is an important cause of respiratory allergy, but the spectrum of known dog allergens appears incomplete. Two lipocalins, Can f 1 and Can f 2, and serum albumin, Can f 3, have been characterized in detail but do not fully account for the IgE antibody-binding activity of dog dander extract. Allergen activity has previously been detected in dog urine but not further characterized. Objective: We sought to identify, characterize, and assess the importance of allergen components in dog urine. Methods: Dog urine was fractionated by means of size exclusion chromatography and examined for IgE antibody binding. A protein present in one fraction displaying IgE antibody-binding activity was identified by means of N-terminal sequencing and mass spectrometry. A recombinant form of the protein was produced in Pichia pastoris. IgE antibody binding to dog allergen components among sera of 37 subjects with dog allergy was determined by means of ImmunoCAP analysis. Results: An IgE antibody-binding protein was isolated from dog urine and identified as prostatic kallikrein. A closely related or identical protein was detected in dog dander. The recombinant prostatic kallikrein displayed immunologic and biochemical properties similar to those of the natural protein and bound IgE antibodies from 26 (70%) of 37 sera of subjects with dog allergy, 14 of which reacted to none of Can f 1, Can f 2, or Can f 3. The dog allergen identified here was found to cross-react with human prostate-specific antigen, a key culprit in IgE-mediated vaginal reactions to semen. Conclusion: Prostatic kallikrein is a new major dog allergen. [Copyright &y& Elsevier]

Background Cough variant asthma is a phenotype of asthma solely presenting with coughing. It involves airway inflammation and remodelling as does classic asthma with wheezing, and a subset of patients may progress to classic asthma. The atopic features of cough variant asthma remain unclear. Objective To compare atopic features between patients with cough variant asthma and those with classic asthma, and to examine the possible correlation of these features with the future development of wheezing in the former group. Methods Total and specific IgE levels of seven common aeroallergens [house dust mite (HDM), Gramineae/Japanese cedar/weed pollens, moulds, cat/dog dander] were examined in 74 cough variant asthma patients and in 115 classic asthma patients of varying severity. Forty of the former patients were prospectively observed for 2 years to determine whether cough variant asthma progressed to classic asthma despite inhaled corticosteroid treatment. Results Patients with classic asthma had higher total IgE ( P<0.0001), larger numbers of sensitized allergens ( P=0.03), and higher rates of sensitization to dog dander (24% vs. 3%, P<0.0001), HDM (46% vs. 28%, P=0.02), and moulds (17% vs. 7%, P=0.047) than did patients with cough variant asthma. Wheezing developed in six (15%) patients with cough variant asthma, who were sensitized to larger numbers of allergens ( P=0.02) and had higher rates of sensitization to HDM ( P=0.01) and dog dander ( P=0.02) than the 34 patients in whom wheezing did not develop. Among the patients with classic asthma, total and specific IgE variables were similar in the subgroup with mild disease ( n=60) and the subgroup with moderate-to-severe disease ( n=55), as reported previously. Conclusions Atopy may be related to the development of wheezing in patients with cough variant asthma. To prevent the progression of cough variant asthma to classic asthma, avoidance of relevant allergens may be essential. [ABSTRACT FROM AUTHOR]

Dong dander and hair (DDHP specific IgA and IgG antibodies form serum samples of 202 asthmatic children aged from 4 to 15 years were measured by enzyme-linked immunosorbend assay. The results were compared with clinical history, and with allergy tests (skin prick test, provocation test and RAST) using the same DDH extract. A blood sample for the in vitro lymphocyte stimulation test was obtained from 40 children, and a nasal secretion sample for analysis of the local DDH-specific IgA, IgG and IgE antibody levels was collected from 35 of them. In children of dog-keeping families, higher serum levels of DDH-specific antibodies, especially IgE antibodies, were observed if the dog had been in the home already during the first years of the child's life. The serum levels of DDH-specific antibodies, however, did not correlate with the degree of the present exposure to dogs. The serum levels of DDH-specific IgA and IgG antibodies did not correlate with each other with the levels of specific or total IgE, or with the results of skin prick or provocation test. The serum levels of DDH-specific IgE correlated positively with serum specific IgE levels. The correlation was weaker between nasal and serum titers of specific IgG, and not significant between nasal and serum IgA antibody levels. Specific IgE antibody levels were higher, while specific IgA and IgG antibody levels were lower in nasal secretion from subjects with nasal symptoms on contact with dogs, when compared with subjects with other complaints (asthma, conjunctival or skin reactions). DDH-specific IgG levels correlated negatively with specific IgE level in the nasal secretion from subjects with a positive provocation test. The in vitro lymphocyte responses to DDH did not correlate with the results of allergy tests, or with the levels of DDH-specific antibodies in serum or in nasal secretion. [ABSTRACT FROM AUTHOR]

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 kU A /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., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)