Major Cat Research Articles

The Major Cat Allergen, Fel d 1, Is a Viable Target for CRISPR Gene Editing.

Allergy to domestic cat (Felis domesticus) affects >10% of the population. Fel d 1, the major cat allergen, causes IgE sensitization in >90% of cat allergic subjects and accounts for 60-90% of anti-cat IgE. Our goal was to identify and target conserved regions of Fel d 1 using CRISPR gene editing, as an approach for ultimately generating allergen-free cats.

Comprehensive mapping of immune tolerance yields a regulatory TNF receptor 2 signature in a murine model of successful Fel d 1-specific immunotherapy using high-dose CpG adjuvant.

BackgroundThe prevalence of allergy to cat is expanding worldwide. Allergen‐specific immunotherapy (AIT) has advantages over symptomatic pharmacotherapy and promises long‐lasting disease control in allergic patients. However, there is still a need to improve cat AIT regarding efficacy, safety, and adherence to the treatment. Here, we aim to boost immune tolerance to the major cat allergen Fel d 1 by increasing the anti‐inflammatory activity of AIT with the established immunomodulatory adjuvant CpG, but at a higher dose than previously used in AIT.MethodsTogether with CpG, we used endotoxin‐free Fel d 1 as therapeutic allergen throughout the study in a BALB/c model of allergy to Fel d 1, thus mimicking the conditions of human AIT trials. Multidimensional immune phenotyping including mass cytometry (CyTOF) was applied to analyze AIT‐specific immune signatures.ResultsWe show that AIT with high‐dose CpG in combination with endotoxin‐free Fel d 1 reverts all major hallmarks of allergy. High‐dimensional CyTOF analysis of the immune cell signatures initiating and sustaining the AIT effect indicates the simultaneous engagement of both, the pDC‐Treg and B‐cell axis, with the emergence of a systemic GATA3+ FoxP3hi biTreg population. The regulatory immune signature also suggests the involvement of the anti‐inflammatory TNF/TNFR2 signaling cascade in NK and B cells at an early stage and in Tregs later during AIT.ConclusionOur results highlight the potential of CpG adjuvant in a novel formulation to be further exploited for inducing allergen‐specific tolerance in patients with cat allergy or other allergic diseases.

СЕНСИБІЛІЗАЦІЯ ДО АЛЕРГЕНІВ ДОМАШНІХ ТВАРИН СЕРЕД ПАЦІЄНТІВ АЛЕРГОЛОГІЧНОЇ КЛІНІКИ

SENSITIZATION TO PET ALLERGENS AMONG THE PATIENTS OF ALLERGOLOGIC CLINIC M. A. Lykova Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine KIA «Forpost», Kyiv, Ukraine Abstract. The aim: to study the prevalence and structure of sensitization to pet allergens among patients of the allergy clinic. Material and methods of research. The results of a multiplex study (determination of specific IgE to 112 allergenic proteins using the ImmunoCap ISAC test system) in 553 patients who came to the immunology and allergology clinic "Forpost" with complaints of respiratory and / or skin manifestations of allergopathology were analyzed. Results. Sensitization to animal allergens was found in 46.1 % of children of group 1 (0–6 years), 62.8 % of children of group 2 (7–18 years) and 42.6 % of adults. Most patients of all ages (96 %) were also sensitized to other (food and / or inhalation) allergens. In all groups of subjects, sensitization to cat allergens prevailed (44.6 % of all animals sensitized to allergens in the group of children 0–6 years, 43.4 % in the group of children 7–18 years, and 42.7 % in the group of adults) and dogs 12.3 %, 6.6 % and 17.7 % respectively). In all age groups, sensitization to the main cat allergen Fel d1 (uteroglobin) prevailed, in children age groups lipocalin also caused a high frequency of sensitization, in particular Can f1 and Fel d4, while in the adult group the frequency of sensitization to prostatic falkrelin canine was in second place. Conclusions. Animal allergens, especially cats and dogs, play an important role in the development of allergic diseases. Most patients with sensitization to one animal species have specific IgE to cat or dog proteins, suggesting that sensitization to horse and mouse allergens may be more frequent due to cross-reactivity. In the structure of sensitization, the most common allergen in all age groups is the major cat allergen Fel d1. In the younger age group, serum albumin is also important, and in adults — prostatic kallikrein Can f5, which should be considered when choosing the appropriate allergen molecules for diagnosis in patients with hypersensitivity to animal allergens before allergen-specific immunotherapy. Key words: hypersensitivity, sensitization, animal allergens, allergic rhinitis, bronchial asthma. Maryana A. Lykova Shupyk National Healthcare University of Ukraine Post-graduate student of the department of phthisiology and pulmonology, KIA «Forpost», physician allergist-immunologist 10, M. Amosova str., 03038, Kyiv, Ukraine, maryana_lykova@ukr.net Аsthma and Allergy, 2021, 3, P. 43–49.

Efficient soluble production of folded cat allergen Fel d 1 in Escherichia coli

The major cat allergen Fel d 1 is one of the most common and potent causes of animal related allergy. Medical treatment of cat allergy has relied on immunotherapy carried out with cat dander extract. This approach has been problematic, mainly due to inconsistent levels of the major allergen in the produced extracts. Recombinant DNA technology has been proposed as an alternative method to produce more consistent pharmaceuticals for immunotherapy and diagnostics of allergy. Current approaches to produce recombinant Fel d 1 (recFel d 1) in the cytoplasm of Escherichia coli have however resulted in protein folding deficiencies and insoluble inclusion body formation, requiring elaborate in vitro processing to acquire folded material. In this study, we introduce an efficient method for cytoplasmic production of recFel d 1 that utilizes eukaryotic folding factors to aid recFel d 1 to fold and be produced in the soluble fraction of E. coli. The solubly expressed recFel d 1 is shown by biophysical in vitro experiments to contain structural disulfides, is extremely stable, and has a sensitivity for methionine sulfoxidation. The latter is discussed in the context of functional relevance.

Immunization of Cats to Induce Neutralizing Antibodies Against Fel D 1, the Major Feline Allergen in Human Subjects

F Thoms, GT Jennings, M Maudrich. J Allergy Clin Immunol . 2019;144(1):193–203 Cats are found in 25% of US households, and 10% of humans are allergic to them. Most cat-allergic subjects make IgE antibody to the major cat allergen Fel d 1. If environmental control measures and medication fail to provide sufficient control of allergic symptoms, allergen immunotherapy can be beneficial. What about immunizing the cat instead? Domestic cats. The cats received a series of 3 intramuscular injections at 3-week intervals of a conjugate vaccine consisting …

IgE-reactivity profiles to allergen molecules in Russian children with and without symptoms of allergy revealed by micro-array analysis.

BackgroundThe analysis of longitudinal birth cohorts with micro‐arrayed allergen molecules has provided interesting information about the evolution of IgE sensitization in children. However, so far no cross‐sectional study has been performed comparing IgE sensitization profiles in children with and without symptoms of allergy. Furthermore, no data are available regarding molecular IgE sensitization profiles in children from Russia.MethodsWe recruited two groups of age‐ and gender‐matched children, one (Group 1: n = 103; 12.24 ± 2.23 years; male/female: 58/45) with symptoms and a second (Group 2: n = 97; 12.78 ± 2.23 years; male/female: 53/44), without symptoms of allergy according to international ISAAC questionnaire. Children were further studied regarding symptoms of allergy (rhinitis, asthma, atopic dermatitis) according to international guidelines, and skin prick testing with a panel of aeroallergen extracts was performed before sera were analyzed in an investigator‐blinded manner for IgE specific to more than 160 micro‐arrayed allergen molecules using ImmunoCAP ISAC technology.ResultsIgE sensitization = or >0.3 ISU to at least one of the micro‐arrayed allergen molecules was found in 100% of the symptomatic children and in 36% of the asymptomatic children. Symptomatic and asymptomatic children showed a comparable IgE sensitization profile; however, frequencies of IgE sensitization and IgE levels to the individual allergen molecules were higher in the symptomatic children. Aeroallergen sensitization was dominated by sensitization to major birch pollen allergen, Bet v 1, and major cat allergen, Fel d 1. Food allergen sensitization was due to cross‐sensitization to PR10 pollen and food allergens whereas genuine peanut sensitization was absent.ConclusionThis is the first study analyzing molecular IgE sensitization profiles to more than 160 allergen molecules in children with and without symptoms of allergy. It detects similar molecular IgE sensitization profiles in symptomatic and asymptomatic children and identifies Bet v 1 and Fel d 1 as the predominant respiratory allergen molecules and PR10 proteins as the major food allergens and absence of genuine peanut allergy in Moscow region (Russia).

Hydro-geochemical Assessment of Seawater Intrusion in Freshwater Shallow Aquifer in Southeastern Coastal of Cuddalore District, Tamilnadu, India

As the coastal line of Tamilnadu is long, it may have been affected due to sea water intrusion by natural (sea level rise) and anthropogenic. Therefore, this study deals with the Hydro chemical assessment of seawater interruption in freshwater aquifer in Parangipettai region. For this assessment, the groundwater samples have been collected in various locations of Parangipettai region for both pre and post-monsoon period. The collected samples were tested by laboratory method for the identification of major cat ions and anions, namely TDS, EC, chloride, magnesium, Bicarbonate, calcium, sodium, potassium, and sulphate. The spatial maps for all the parameters were carried out using the ArcGIS 10.2 version for the purpose of better understanding the quality of groundwater. The results obtained through laboratory method are used to create Salinity and sodium risk of irrigation water in US salinity diagram, Gibbs diagram, permeability index and reconstructed diamond field of piper diagram using the watclast software. From the spatial maps, watclast diagrams and the standards recommended by WHO, BIS, and ISI, the SWI are discussed in detail to recommend the remedial measures to recover and restore the feature of groundwater in the Parangipettai region.

Atopic Patients Who Fulfilled Rome III Criteria for Irritable Bowel Syndrome Had Higher Animal Danders Sensitization.

Background/AimsThe relationship between animal exposure and irritable bowel syndrome (IBS) is debated. Epidemiological studies have shown that atopy is more prevalent in IBS patients and vice versa. We set out to examine the association between animal danders sensitization and IBS-like symptoms in atopic patients.MethodsWe recruited 69 consecutive atopic patients from the allergy clinic of a tertiary hospital. Subjects completed validated bowel questionnaires, underwent skin prick test, blood was collected for serum total immunoglobulin E, and ImmunoCAP immune solid-phase allergen chip (ISAC) IgE multiplex assay.ResultsTwenty-eight (41.0%) atopic patients fulfilled the Rome III IBS criteria (atopy-IBS). There were no differences in gender, age, pet ownership, total serum IgE, or food allergen sensitization between atopy-IBS group and atopy-non-IBS group. We found that atopy-IBS group had significantly higher number of positive skin prick test for cat dander (64.3% vs 24.4%, P < 0.001), dog dander (64.3% vs 41.5%, P = 0.015) and weed pollens (32.1% vs 14.6%, P = 0.050) compared to atopy-non-IBS group. Out of 112 components from 51 allergen sources (both aeroallergen and food allergens), only Fel d1 (a major cat dander antigen) IgE is significantly higher in atopy-IBS group than atopy-non-IBS group (21.4% vs 2.4%, P = 0.029). Majority of atopy-IBS patients had mixed-type IBS.ConclusionsWe demonstrated an association between animal danders sensitization, in particular cat dander sensitization, and IBS-like symptoms in atopic patients. Future studies are needed to explore the relationship between aeroallergen and functional gastrointestinal disorders. Sensitization may be related to the pathophysiology of IBS or it could be that we are missing aeroallergen-induced gut allergy.

Immunization of Cats against Fel d 1 Results in Reduced Allergic Symptoms of Owners.

An innovative approach was tested to treat cat allergy in humans by vaccinating cats with Fel-CuMV (HypoCatTM), a vaccine against the major cat allergen Fel d 1 based on virus-like particles derived from cucumber mosaic virus (CuMV-VLPs). Upon vaccination, cats develop neutralizing antibodies against the allergen Fel d 1, which reduces the level of reactive allergen, thus lowering the symptoms or even preventing allergic reactions in humans. The combined methodological field study included ten cat-allergic participants who lived together with their cats (n = 13), that were immunized with Fel-CuMV. The aim was to determine methods for measuring a change in allergic symptoms. A home-based provocation test (petting time and organ specific symptom score (OSSS)) and a general weekly (or monthly) symptom score (G(W)SS) were used to assess changes in allergic symptoms. The petting time until a pre-defined level of allergic symptoms was reached increased already early after vaccination of the cats and was apparent over the course of the study. In addition, the OSSS after provocation and G(W)SS recorded a persistent reduction in symptoms over the study period and could serve for long-term assessment. Hence, the immunization of cats with HypoCatTM (Fel-CuMV) may have a positive impact on the cat allergy of the owner, and changes could be assessed by the provocation test as well as G(W)SS.

An odor-reducing, low dust-forming, clumping cat litter produced from Eastern red cedar (Juniperus virginiana L.) wood fibers and biochar1

Biobased cat litters made of a variety of materials are currently sold internationally, as many cat owners are concerned with disposal problems encountered with traditional inorganic clay-based litters as well as the fact that cats might harm themselves by ingesting these litters or by inhaling clay dust. Several commercially-available cat litters contain Eastern red cedar (ERC), Juniperus virginiana L., wood fibers as a major constituent. ERC fibers contain sesquiterpenes that have been shown to be toxic to fleas and ticks. The objective of this research was to determine if ERC fibers combined with ERC biochar at 1, 5 and 10 % (w/w%) would produce an odor-reducing, biodegradable cat litter. Sieving ERC fibers and adding mineral oil significantly reduced release of dust (< 10 μm) particles. Addition of juniper biochar reduced headspace levels of 3-mercapto-3-methylbutan-1-ol (MMB), the major offensive cat urine volatile odor compound. Addition of 250 ppm copper sulfate to the litter formulations did not result in a significant decrease in headspace MMB compared to the litter containing 10 % ERC biochar. All litter formulations had high hydration capacities (the ability to absorb liquids), and with the addition of guar gum as a clumping agent the litter formulation containing 10 % ERC biochar had the most desirable physical and chemical properties for development as a commercial cat litter.

The Major Cat Allergen Fel d 1 Binds Steroid and Fatty Acid Semiochemicals: A Combined In Silico and In Vitro Study.

The major cat allergen Fel d 1 is a tetrameric glycoprotein of the secretoglobin superfamily. Structural aspects and allergenic properties of this protein have been investigated, but its physiological function remains unclear. Fel d 1 is assumed to bind lipids and steroids like the mouse androgen-binding protein, which is involved in chemical communication, either as a semiochemical carrier or a semiochemical itself. This study focused on the binding activity of a recombinant model of Fel d 1 (rFel d 1) towards semiochemical analogs, i.e., fatty acids and steroids, using both in silico calculations and fluorescence measurements. In silico analyses were first adopted to model the interactions of potential ligands, which were then tested in binding assays using the fluorescent reporter N-phenyl-1-naphthylamine. Good ligands were fatty acids, such as the lauric, oleic, linoleic, and myristic fatty acids, as well as steroids like androstenone, pregnenolone, and progesterone, that were predicted by in silico molecular models to bind into the central and surface cavities of rFel d 1, respectively. The lowest dissociation constants were shown by lauric acid (2.6 µM) and androstenone (2.4 µM). The specific affinity of rFel d 1 to semiochemicals supports a function of the protein in cat’s chemical communication, and highlights a putative role of secretoglobins in protein semiochemistry.

Hello, kitty: could cat allergy be a form of intoxication?

Background:The relationship between slow loris (Nycticebus spp.) venom (BGE protein) and the major cat allergen (Fel d 1) from domestic cat (Felis catus) is known for about two decades. Along this time, evidence was accumulated regarding convergences between them, including their almost identical mode of action. Methods:Large-scale database mining for Fel d 1 and BGE proteins in Felidae and Nycticebus spp., alignment, phylogeny proposition and molecular modelling, associated with directed literature review were assessed. Results:Fel d 1 sequences for 28 non-domestic felids were identified, along with two additional loris BGE protein sequences. Dimer interfaces are less conserved among sequences, and the chain 1 shows more sequence similarity than chain 2. Post-translational modification similarities are highly probable. Conclusions:Fel d 1 functions beyond allergy are discussed, considering the great conservation of felid orthologs of this protein. Reasons for toxicity being found only in domestic cats are proposed in the context of domestication. The combination of the literature review, genome-derived sequence data, and comparisons with the venomous primate slow loris may point to domestic cats as potentially poisonous mammals.

Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen.

BackgroundAllergies to cats are the most common animal‐origin allergy, and affect approximately 1 in 5 adults worldwide. The prevalence of allergy to furry animals has been increasing, and allergy to cats is a major risk factor for the development of asthma and rhinitis. The diagnosis of cat allergy is now well established. The exact significance of component‐resolved diagnosis in the diagnosis of cat allergy remains to be fully understood. Allergen avoidance is effective but often has a psychologic impact. Allergen immunotherapy is not well demonstrated. There is a need for innovative approaches to better manage cat allergens. Next‐generation care pathways for asthma and rhinitis will define the place of cat allergen avoidance.Methods and ResultsThis manuscript, based on content presented at the European Academy of Allergy and Clinical Immunology Congress 2019, provides information on the prevalence and impact of cat allergies and the molecular biology of Fel d 1, the major cat allergen.DiscussionThe authors present the scientific basis of a novel care pathway that utilizes anti‐Fel d 1 IgY antibodies to safely and effectively neutralize Fel d 1 after its production by the cat but before human exposure.ConclusionEfficacy of a feline diet with an egg product ingredient containing anti‐Fel d 1 IgY antibodies was demonstrated in vitro, ex vivo, and in vivo, and further validated by a pilot exposure study involving cat‐allergic human participants.

Modulation of CRTh2 expression on allergen-specific T cells following peptide immunotherapy.

BackgroundAllergen immunotherapy using synthetic peptide T‐cell epitopes (Cat‐PAD) from the major cat allergen Fel d 1 has been shown, in allergen exposure studies, to significantly reduce symptoms of allergic rhinoconjunctivitis in cat‐allergic subjects. However, the immunological mechanisms underlying clinical benefit remain only partially understood. Since previous studies of whole allergen immunotherapy demonstrated a reduction in the frequency of allergen‐specific (MHC II tetramer+) CD4+ T cells expressing the chemokine receptor CRTh2, we assessed the impact of Cat‐PAD on the frequency and functional phenotype of Fel d 1‐specific CD4+ T cells.MethodsUsing before and after treatment samples from subjects enrolled in a randomized, double‐blind, placebo‐controlled trial of Cat‐PAD, we employed Fel d 1 MHC II tetramers and flow cytometry to analyze the expression of chemokine receptors CCR3, CCR4, CCR5, CXCR3, and CRTh2, together with markers of memory phenotype (CD27 and CCR7) on Fel d 1‐specific CD4+ T cells.ResultsNo statistically significant change in the frequency of Fel d 1‐specific CD4+ T cells, nor in their expression of chemokine receptors or memory phenotype, was observed. However, a significant reduction in cell surface expression of CRTh2 was observed between the placebo and active groups (P = 0.047).ConclusionsPeptide immunotherapy with Cat‐PAD does not significantly alter the frequency or phenotype of Fel d 1‐CD4+ T cells, but may decrease their expression of CRTh2.

Immunization of cats to induce neutralizing antibodies against Fel d 1, the major feline allergen in human subjects

Cat allergy in human subjects is usually caused by the major cat allergen Fel d 1 and is found in approximately 10% of the Western population. Currently, there is no efficient and safe therapy for cat allergy available. Allergic patients usually try to avoid cats or treat their allergy symptoms. We developed a new strategy to treat Fel d 1-induced allergy in human subjects by immunizing cats against their own major allergen, Fel d 1. A conjugate vaccine consisting of recombinant Fel d 1 and a virus-like particle derived from the cucumber mosaic virus containing the tetanus toxin-derived universal T-cell epitope tt830-843 (CuMVTT) was used to immunize cats. Afirst tolerability and immunogenicity study, including a boost injection, was conducted by using the Fel-CuMVTT vaccine alone or in combination with an adjuvant. The vaccine was well tolerated and had no overt toxic effect. All cats induced a strong and sustained specific IgG antibody response. The induced anti-Fel d 1 antibodies were of high affinity and exhibited a strong neutralization ability tested both invitro and invivo. Areduction in the endogenous allergen level and a reduced allergenicity of tear samples, were observed. Vaccination of cats with Fel-CuMVTT induces neutralizing antibodies and might result in reduced symptoms of allergic cat owners. Both human subjects and animals could profit from this treatment because allergic cat owners would reduce their risk of developing chronic diseases, such as asthma, and become more tolerant of their cats, which therefore could stay in the households and not need to be relinquished to animal shelters.

Crystal structure of the dog allergen Can f 6 and structure-based implications of its cross-reactivity with the cat allergen Fel d 4

Several dog allergens cause allergic reactions in humans worldwide. Seven distinct dog allergens, designated Canis familiaris allergen 1 to 7 (Can f 1–Can f 7), have been identified thus far. Can f 6 shows high sequence similarity and cross-reactivity with Fel d 4 and Equ c 1, major cat and horse allergens, respectively. This study was conducted on the allergenic epitopes of Can f 6 based on its structural characterization. We demonstrated that sera from 18 out of 38 (47%) dog-sensitized patients reacted to recombinant Can f 6 protein (rCan f 6). We then determined the crystal structure of rCan f 6 by X-ray crystallography, which exhibited a conserved tertiary structural architecture found in lipocalin family proteins. Based on the tertiary structure and sequence similarities with Fel d 4 and Equ c 1, we predicted three IgE-recognizing sites that are possibly involved in cross-reactivity. Substituting three successive amino acids in these sites to triple alanine decreased IgE reactivity to the allergen. However, the degree of reduction in IgE reactivity largely depended on the site mutated and the serum used, suggesting that Can f 6 is a polyvalent allergen containing multiple epitopes and Can f 6-reactive sera contain varied amounts of IgE recognising individual Can f 6 epitopes including those predicted in this study. We also demonstrated that the predicted epitopes are partly involved in IgE cross-reactivity to Fel d 4. Interestingly, the effect of the mutation depended on whether the protein was structured or denatured, indicating that the bona fide tertiary structure of Can f 6 is essential in determining its IgE epitopes.

Allergic manifestations in patients with sensitization to cat allergens

Relevance. Cats and dogs are the most popular pets in many countries, what leads to a high and widespread prevalence of their allergens and increase of sensitization to animal allergens with tendency of changing the dominant profile of sensitization with the predominance of the major cat allergen. The purpose of this study was to assess the severity of allergic rhinitis and its combination with other forms of allergic diseases in children sensitized to cat allergens. Materials and methods. Under our supervision there were 228 children aged 3-16 years old living in the cities of the Sverdlovsk region. Evaluation of the sensitization spectrum was carried out according to the results of prick tests and the level of sIgE by immunofluorescence method. Results. All children had manifestations of persistent allergic rhinitis. In 42.1% (n=96) of cases the upper and lower respiratory tract comorbidities were detected, in 16.6% (n=38) - manifestations of atopic dermatitis. In 65.4% (n=149) of children the total level of points on the SFAR scale was

Evaluation of the manufacturer-dependent differences in specific immunoglobulin E results for indoor allergens

BackgroundEven though allergies are an important health issue, the detected amount of allergen-specific IgE (sIgE) has differed widely between manufacturers in the past, and even as recently as this year. These discrepancies hinder diagnostics and can even impact allergen immunotherapy. ObjectiveThe aim of this study was to evaluate the development and status quo of the quality of in vitro diagnostic testing for house dust mites (HDM) and cat epithelium, 2 important indoor allergen sources. MethodsWe analyzed data on the allergen sources European HDM, American HDM, and cat epithelium, which were collected by the Society for Promoting Quality Assurance in Medical Laboratories (INSTAND e.V.) during 7 years as part of External Quality Assessment schemes (EQAs). A pseudoanonymized comparison was made of the semiquantitative data and allergen-class results of the 4 main suppliers of in vitro diagnostic sIgE tests. Coefficients of variation (CV) were determined in order to evaluate interlaboratory comparability. ResultsIn vitro allergy diagnostic testing for the major allergen sources HDM and cat epithelium still reveals manufacturer-dependent differences. Despite this, a cautious trend was found towards an alignment of the results and interlaboratory comparability, with the exception of 1 supplier. ConclusionEven though these results are promising, future EQAs have to be closely monitored to ensure this positive trend is not just a snapshot.

Induction of bystander tolerance and immune deviation after Fel d 1 peptide immunotherapy

Treatment of patients with cat allergy with peptides derived from Fel d 1 (the major cat allergen) ameliorated symptoms of cat allergy in phase 2 clinical trials. We sought to demonstrate that the tolerance induced by Fel d 1 peptide immunotherapy can be exploited to reduce allergic responses to a second allergen, ovalbumin (OVA), in mice sensitized dually to OVA and Fel d 1. Induction of tolerance to OVA was achieved through simultaneous exposure to both allergens after peptide treatment. Functional tolerance to each allergen was assessed in a model of allergic airways disease in which treated mice were protected from eosinophilia, goblet cell hyperplasia, and TH2 cell infiltration. Suppression of allergic responses to cat allergen challenge was associated with significant increases in numbers of CD4+CD25+Foxp3+ T cells, IL-10+ cells, and CD19+IL-10+ B cells, whereas the response to OVA was associated with a marked reduction in numbers of TH2 cytokine-secreting T cells and less prominent changes in outcomes associated with immune regulation. These observations suggest that immune tolerance induced by peptide immunotherapy can be used experimentally to treat an allergic response to another allergen and that the molecular mechanisms underlying induction of tolerance to a treatment-specific allergen and a bystander allergen might be different.

Another cat and mouse game: Deciphering the evolution of the SCGB superfamily and exploring the molecular similarity of major cat allergen Fel d 1 and mouse ABP using computational approaches.

The mammalian secretoglobin (SCGB) superfamily contains functionally diverse members, among which the major cat allergen Fel d 1 and mouse salivary androgen-binding protein (ABP) display similar subunits. We searched for molecular similarities between Fel d 1 and ABP to examine the possibility that they play similar roles. We aimed to i) cluster the evolutionary relationships of the SCGB superfamily; ii) identify divergence patterns, structural overlap, and protein-protein docking between Fel d 1 and ABP dimers; and iii) explore the residual interaction between ABP dimers and steroid binding in chemical communication using computational approaches. We also report that the evolutionary tree of the SCGB superfamily comprises seven unique palm-like clusters, showing the evolutionary pattern and divergence time tree of Fel d 1 with 28 ABP paralogs. Three ABP subunits (A27, BG27, and BG26) share phylogenetic relationships with Fel d 1 chains. The Fel d 1 and ABP subunits show similarities in terms of sequence conservation, identical motifs and binding site clefts. Topologically equivalent positions were visualized through superimposition of ABP A27:BG27 (AB) and ABP A27:BG26 (AG) dimers on a heterodimeric Fel d 1 model. In docking, Fel d 1-ABP dimers exhibit the maximum surface binding ability of AG compared with that of AB dimers and the several polar interactions between ABP dimers with steroids. Hence, cat Fel d 1 is an ABP-like molecule in which monomeric chains 1 and 2 are the equivalent of the ABPA and ABPBG monomers, respectively. These findings suggest that the biological and molecular function of Fel d 1 is similar to that of ABP in chemical communication, possibly via pheromone and/or steroid binding.