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Platts-Mills TA, Keshavarz B, Wilson JM, Rifas-Shiman SL, Ailsworth SM, Sordillo JE, Workman L, Chapman M, Lidholm J, Oken E, Gold DR. High risk of asthma among early teens is associated with quantitative differences in mite and cat allergen specific IgE and IgG4: a modified Th2 related antibody response revisited. EBioMedicine 2025; 112:105556. [PMID: 39893721 PMCID: PMC11840499 DOI: 10.1016/j.ebiom.2024.105556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 12/06/2024] [Accepted: 12/31/2024] [Indexed: 02/04/2025] Open
Abstract
BACKGROUND Although proteins derived from cats are an important contributor to indoor allergen exposure in relation to asthma, it has been known for at least twenty years that some children who live in a house with a cat can become clinically tolerant to these animals. In 2001, we reported that children exposed to high levels of cat allergens made high levels of IgG4 antibodies to the cat allergen Fel d 1, and we coined the term "a modified Th2 response". However, this phenomenon is still poorly understood. METHODS We studied serum antibodies among 616 individuals in the Viva unselected birth cohort recruited at their early teen visit (mean age 13.1 SD 0.8). IgE and IgG4 antibodies were measured by ImmunoCAP to inhaled allergens as well as the best characterised component allergens of cat, Fel d 1, Fel d 2, Fel d 4, and Fel d 7, and the dust mite allergens Der p 1, Der p 2, Der p 10, and Der p 23. FINDINGS The results confirm that young teens living in a home with a cat make high levels of IgG4 specific for cat allergens, and that those antibodies, and specifically those to Fel d 1 are negatively associated with asthma. By contrast, the IgG4 responses to Fel d 4 and Fel d 7 are significantly lower and have no significant association with asthma. Perhaps more surprisingly, a similar effect is seen in relation to dust-mite allergens. Although the allergen Der p 1 is a major part of the IgE response to mite allergens, this protein also induced high prevalence and levels of IgG4 antibodies and has a less strong relationship to asthma than IgE to Der p 2 or Der p 23. Indeed, values of specific IgE to Der p 1 >3.5 IU/mL were not significantly related to asthma (OR 1.5 CI 0.8-2.8, p = 0.3, Chi2 test). The prevalence and levels of specific IgG4 to these less abundant allergens are significantly lower for Der p 2 and almost absent for Der p 23. INTERPRETATION High exposure to specific allergens in household dust can enhance production of both sIgE and sIgG4 antibodies, while allergens where abundance is significantly lower in dust can induce sIgE with limited or no sIgG4. The result is that the less abundant allergens, i.e., Fel d 4, Fel d 7, Der p 2, and Der p 23, may have a significantly higher relevance to asthma than expected because they induce less sIgG4. FUNDING This work was funded by R01-AI20565 (TPM) and support for the IgE and IgG4 assays provided by Phadia/Thermo Fisher Kalamazoo, Michigan. Project Viva is also supported by NIH R01HD034568 and R24ES.
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Affiliation(s)
- Thomas A Platts-Mills
- Division of Allergy & Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
| | - Behnam Keshavarz
- Division of Allergy & Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, USA
| | - Jeffrey M Wilson
- Division of Allergy & Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, USA
| | - Sheryl L Rifas-Shiman
- The Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Samuel M Ailsworth
- Division of Allergy & Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, USA
| | - Joanne E Sordillo
- The Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Lisa Workman
- Division of Allergy & Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, USA
| | | | | | - Emily Oken
- The Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Diane R Gold
- The Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; The Department of Environmental Medicine, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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Uenoyama R, Zhu W, Miura M, Miyazaki T, Miyazaki M. Sprayed Urine Emits a Pungent Odor due to its Increased Adhesion to Vertical Objects via Urinary Proteins Rather Than to Changes in its Volatile Chemical Profile in Domestic Cats. J Chem Ecol 2024; 50:978-993. [PMID: 38600408 DOI: 10.1007/s10886-024-01490-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 02/14/2024] [Accepted: 03/18/2024] [Indexed: 04/12/2024]
Abstract
Spraying urine on vertical objects by raising the tail is a commonly observed functional behavior for chemical communication in Felidae species, including domestic cats (Felis silvestris catus). The sprayed urine is recognized as a chemical signal for territorial ownership of their habitats. Previous studies reported that sprayed urine emits a more pungent odor than urine excreted from a squatting position. However, little is known about how sprayed urine acts as a strong scent mark in the environment. Here, we showed that sprayed urine originates only from bladder urine without any secretions, such as anal sac secretions, but it can effectively emit volatile organic compounds (VOCs) when smeared on vertical objects due to its strong adhesion. Chemical profiles of VOCs and odor qualities were similar between fresh sprayed urine and bladder urine sampled immediately after spraying from the same individuals. Meanwhile, feline-specific proteinuria arising from excretion of a carboxylesterase that produces a precursor of cat-specific odorants resulted in reduced surface tension of the urine and increased adhesion to vertical surfaces, which kept sprayed urine on the surfaces and led to the emission of large amounts of VOCs. In conclusion, proteinuria contributes to the emission of a strong odor through its enhanced adhesion to vertical objects without other secretions containing malodorous substances. These findings improve our understanding of the mechanism of scent marking via the spraying of urine for chemical communication in cats.
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Affiliation(s)
- Reiko Uenoyama
- The United Graduate School of Agricultural Sciences, Iwate University, 3-18-8 Ueda, Morioka, Iwate, 020-8550, Japan
| | - Wenrui Zhu
- The United Graduate School of Agricultural Sciences, Iwate University, 3-18-8 Ueda, Morioka, Iwate, 020-8550, Japan
| | - Makoto Miura
- The United Graduate School of Agricultural Sciences, Iwate University, 3-18-8 Ueda, Morioka, Iwate, 020-8550, Japan
- Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, Iwate, 020-8550, Japan
| | - Tamako Miyazaki
- Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, Iwate, 020-8550, Japan
| | - Masao Miyazaki
- The United Graduate School of Agricultural Sciences, Iwate University, 3-18-8 Ueda, Morioka, Iwate, 020-8550, Japan.
- Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, Iwate, 020-8550, Japan.
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Schroers M, Meyer-Lindenberg A. Performance and overview of clinically relevant areas of application of saliva testing in the cat. Front Vet Sci 2024; 11:1385345. [PMID: 38840640 PMCID: PMC11150842 DOI: 10.3389/fvets.2024.1385345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 05/10/2024] [Indexed: 06/07/2024] Open
Abstract
Introduction The cat represents an important model in order to investigate basic physiological knowledge of salivary secretion as well as pharmacokinetics of active substances. Objective The aim of the study was to review in which diagnostic application areas saliva testing is routinely used and in which areas it could be further explored in the future. Materials and methods Literature relevant to the research question was collected in March 2022 using the Pubmed database. Results The diagnosis of infectious diseases in cat saliva is one of the most important fields of application. Saliva diagnostics may also indicate dental diseases, allergies or kidney and other metabolic diseases. Sexual and stress hormones can also be measured in cat saliva. A number of clinically relevant allergens in cat saliva that may cause allergies in humans has been investigated and described, in addition to infectious agents that can be transmitted from cats to humans. Conclusions Saliva testing in cats can be useful in many areas, including the detection of infectious diseases, allergies and dental disease. However, it is far from being used to its full potential within veterinary medicine.
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Affiliation(s)
- Maike Schroers
- Clinic of Small Animal Surgery and Reproduction, Veterinary Faculty, Ludwig-Maximilians-University Munich, Munich, Germany
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Hedrick ED, Matulka RA, Conboy-Schmidt L, May KA. Evaluation of anti-Fel d 1 IgY ingredient for pet food on growth performance in kittens. Front Vet Sci 2024; 11:1355390. [PMID: 38505000 PMCID: PMC10948519 DOI: 10.3389/fvets.2024.1355390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 02/22/2024] [Indexed: 03/21/2024] Open
Abstract
Introduction The domestic cat (Felis catus) is one of the most common pets. Worldwide, approximately one in five adults are sensitive to cat allergens. The major cat allergen is the secretoglobulin Fel d 1, which is primarily produced in the salivary and sebaceous glands. Chickens produce IgY antibodies, which are similar in structure to mammalian IgG. When chickens are exposed to Fel d 1, anti-Fel d 1-specific IgY (AFD1) is produced and is naturally concentrated in egg yolk. The aim of this study was to evaluate the tolerability, effects on growth and food consumption, and potential adverse effects of a chicken egg product ingredient containing AFD1 in kittens. Methods This was a blinded, controlled study. Twenty-seven (27) eight-week old kittens were randomly assigned to three feeding groups containing 0 ppm AFD1 (Group 0), 8 ppm AFD1 (Group 1), and 16 ppm AFD1 (Group 2) for 84 days. Veterinary exams and bloodwork were performed on Day 42 and Day 84, and body weight and body condition score (BCS) were monitored weekly. Results Throughout the study, there were no signs of nutritional deficiency or adverse clinical events in any of the subjects. Administration of a chicken egg product ingredient containing AFD1 in the diet (whether in coating or combination of coating and top dress) had no significant effect on body weight nor food consumption, and all subjects maintained a healthy Body Condition Score (BCS) throughout the study. Moreover, there were no biologically significant differences in the mean clinical chemistry and hematology parameters. Discussion This study demonstrated that a diet formulated to contain up to 16 ppm AFD1, included in the coating and the top-dress of dry kitten food, was well tolerated, promoted adequate growth, and exhibited no adverse effects.
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Matsuura R, Kawamura A, Ota R, Fukushima T, Fujimoto K, Kozaki M, Yamashiro M, Somei J, Matsumoto Y, Aida Y. TiO 2-Photocatalyst-Induced Degradation of Dog and Cat Allergens under Wet and Dry Conditions Causes a Loss in Their Allergenicity. TOXICS 2023; 11:718. [PMID: 37624223 PMCID: PMC10458468 DOI: 10.3390/toxics11080718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 08/11/2023] [Accepted: 08/19/2023] [Indexed: 08/26/2023]
Abstract
Allergies to dogs and cats can cause enormous damage to human health and the economy. Dog and cat allergens are mainly found in dog and cat dander and are present in small particles in the air and in carpets in homes with dogs and cats. Cleaning houses and washing pets are the main methods for reducing allergens in homes; however, it is difficult to eliminate them completely. Therefore, we aimed to investigate whether a TiO2 photocatalyst could degrade dog and cat allergens. Under wet conditions, exposure to the TiO2 photocatalyst for 24 h degraded Can f1, which is a major dog allergen extracted from dog dander, by 98.3%, and Fel d1, which is a major cat allergen extracted from cat dander, by 93.6-94.4%. Furthermore, under dry conditions, the TiO2 photocatalyst degraded Can f1 and Fel d1 by 92.8% and 59.2-68.4%, respectively. The TiO2 photocatalyst abolished the binding of dog and cat allergens to human IgE by 104.6% and 108.6%, respectively. The results indicated that the TiO2 photocatalyst degraded dog and cat allergens, causing a loss in their allergenicity. Our results suggest that TiO2 photocatalysis can be useful for removing indoor pet allergens and improving the partnership between humans and pets.
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Affiliation(s)
- Ryosuke Matsuura
- Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan; (R.M.)
| | - Arisa Kawamura
- Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan; (R.M.)
| | - Rizo Ota
- Inuyama Animal General Medical Center, 29 Oomishita, Haguro, Inuyama 484-0894, Japan
| | - Takashi Fukushima
- Kaltech Corporation, Hirotake Bldg. 3-3-7 Bakuromachi, Chuo-ku, Osaka 541-0059, Japan
| | - Kazuhiro Fujimoto
- Kaltech Corporation, Hirotake Bldg. 3-3-7 Bakuromachi, Chuo-ku, Osaka 541-0059, Japan
| | - Masato Kozaki
- Kaltech Corporation, Hirotake Bldg. 3-3-7 Bakuromachi, Chuo-ku, Osaka 541-0059, Japan
| | - Misaki Yamashiro
- Kaltech Corporation, Hirotake Bldg. 3-3-7 Bakuromachi, Chuo-ku, Osaka 541-0059, Japan
| | - Junichi Somei
- Kaltech Corporation, Hirotake Bldg. 3-3-7 Bakuromachi, Chuo-ku, Osaka 541-0059, Japan
| | - Yasunobu Matsumoto
- Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan; (R.M.)
- Laboratory of Global Animal Resource Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Yoko Aida
- Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan; (R.M.)
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Özuygur Ermis SS, Norouzi A, Borres MP, Basna R, Ekerljung L, Malmhäll C, Goksör E, Wennergren G, Rådinger M, Lötvall J, Kankaanranta H, Nwaru BI. Sensitization patterns to cat molecular allergens in subjects with allergic sensitization to cat dander. Clin Transl Allergy 2023; 13:e12294. [PMID: 37632243 PMCID: PMC10422092 DOI: 10.1002/clt2.12294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 07/21/2023] [Accepted: 07/31/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND The use of molecular allergology has increasingly become common in the diagnosis and management of allergic diseases. However, there is still a lack of data on cat molecular allergens in adults. Therefore, we aimed to uncover the sensitization patterns to cat molecular allergens. METHODS Participants were recruited from the West Asthma Sweden Study, a population-based study enriched with asthma subjects aged 16-75 years. Of 1872, 361 individuals were positive for cat dander immunoglobulin E and were further analysed for cat molecular allergens (Fel d 1/2/4/7). Sensitization patterns were classified as monosensitization, polysensitization, and concomitant sensitization, and were related to demographic and clinical measurements. RESULTS Among cat-sensitized subjects, 84.2% were sensitized to secretoglobin, while 42.4% were sensitized to lipocalins. Nearly half of the subjects were monosensitized to Fel d 1. Polysensitization was observed in 20.2%, and concomitant sensitization to protein families was seen in 7.2%. Asthma prevalence, cat exposure, and rural living were associated with poly- and concomitant sensitization to protein families. Concomitant sensitization to single allergens was more common in those with asthma than in those without, while concomitant sensitization to both Fel d 1 and Fel d 4 was the most common pattern in individuals with asthma. Sensitization patterns also differed according to cat ownership and the degree of urbanization. CONCLUSION Sensitization to molecular allergens was observed in 90.9% of cat-sensitized subjects and showed variations across participants' background characteristics and the presence of asthma. Identification of sensitization patterns to cat allergens might provide better characterization of cat-allergic subjects.
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Affiliation(s)
- Saliha Selin Özuygur Ermis
- Krefting Research CentreInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | | | - Magnus P. Borres
- ImmunoDiagnosticsThermo Fisher ScientificUppsalaSweden
- Department of Maternal and Child HealthUppsala UniversityUppsalaSweden
| | - Rani Basna
- Krefting Research CentreInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Linda Ekerljung
- Krefting Research CentreInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Carina Malmhäll
- Krefting Research CentreInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Emma Goksör
- Department of PediatricsQueen Silvia Children's HospitalUniversity of GothenburgGothenburgSweden
| | - Göran Wennergren
- Department of PediatricsQueen Silvia Children's HospitalUniversity of GothenburgGothenburgSweden
| | - Madeleine Rådinger
- Krefting Research CentreInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Jan Lötvall
- Krefting Research CentreInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Hannu Kankaanranta
- Krefting Research CentreInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Faculty of Medicine and Life SciencesUniversity of TampereTampereFinland
- Department of Respiratory MedicineSeinäjoki Central HospitalSeinäjokiFinland
| | - Bright I. Nwaru
- Krefting Research CentreInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Wallenberg Centre for Molecular and Translational MedicineInstitute of MedicineUniversity of GothenburgGothenburgSweden
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Durairaj R, Pageat P, Bienboire-Frosini C. Impact of Semiochemicals Binding to Fel d 1 on Its 3D Conformation and Predicted B-Cell Epitopes Using Computational Approaches. Int J Mol Sci 2023; 24:11685. [PMID: 37511444 PMCID: PMC10380945 DOI: 10.3390/ijms241411685] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/12/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
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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Affiliation(s)
- Rajesh Durairaj
- Department of Bioinformatics and Chemical Communication (D-BICC), Research Institute in Semiochemistry and Applied Ethology (IRSEA), Quartier Salignan, 84400 Apt, France
| | - Patrick Pageat
- Research and Education Board, Research Institute in Semiochemistry and Applied Ethology (IRSEA), Quartier Salignan, 84400 Apt, France
| | - Cécile Bienboire-Frosini
- Department of Molecular Biology and Chemical Communication (D-BMCC), Research Institute in Semiochemistry and Applied Ethology (IRSEA), Quartier Salignan, 84400 Apt, France
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Sex Differences in Mouse Exploratory Behaviour to Fel d 1, a Cat ABP-Like Protein. Animals (Basel) 2021; 11:ani11113149. [PMID: 34827881 PMCID: PMC8614430 DOI: 10.3390/ani11113149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/23/2021] [Accepted: 11/03/2021] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Fel d 1 is a cat secreted protein, known as the main cat allergen, that is abundantly released and found in their habitat. Cats are one of the main predators of rodents and have been historically used to control rodent populations in human habitats. We assumed that laboratory mice, as a model of wild mice, would be able to detect and avoid this abundant cat molecule as a mechanism to increase chances of survival. In our study, we compared mice exploratory behaviours facing Fel d 1, a fox faeces molecule (TMT) as a positive control, and a negative control (purified water). We found that mice did not avoid Fel d 1 as we expected; however, male mice remained in the area with Fel d 1 longer than females. These results give interesting insights about how sexes can react differently to a predator stimulus and give support to the use of both sexes in behavioural studies, and more precisely in predator-prey interactions research Abstract Fel d 1 is a cat protein abundantly released and found in their habitat and is closely related to mouse androgen-binding proteins (ABPs). We hypothesized that mice have developed chemical communication mechanisms to detect and avoid this protein. We tested purified natural Fel d 1, a fox faeces molecule (TMT) as a positive control, and a negative control (purified water) in three different mouse groups (n = 14 each) to evaluate exploratory behaviour and stress responses. The mice did not show clear avoidance or stress responses to Fel d 1. Our results demonstrated a sex-treatment interaction for Fel d 1, with males spending more time in the areas treated with Fel d 1 than in the untreated areas (p = 0.018). This sex-treated area interaction was also not observed for either the blank or TMT. These results suggest that Fel d 1 from domestic cats could be recognized differently by male and female mice. These sex differences could be linked to the sexual role of ABP proteins and the ABP-like characteristics of Fel d 1.
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Popescu FD, Ganea CS, Panaitescu C, Vieru M. Molecular diagnosis in cat allergy. World J Methodol 2021; 11:46-60. [PMID: 34026578 PMCID: PMC8127422 DOI: 10.5662/wjm.v11.i3.46] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/22/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
Domestic cats represent one of the most common sources of indoor allergens. All over the world, many households own cats, whose allergens are persistent and widespread. Cat allergy itself is frequent, and its symptoms vary from rhinoconjunctivitis to life-threatening asthma. In vitro diagnosis using precision medicine allergy immunoassays is important because natural cat dander extracts may differ in quality and quantity of some of the individual allergen components and other molecules. In the component-resolved diagnosis of cat allergy, singleplex and multiplex specific immunoglobulin (Ig) E assays include use of the cat-specific major allergen, secretoglobin Fel d 1 (as a species-specific molecule), other allergen components (such as lipocalins Fel d 4, cross-reacting with other animal similar molecules, and Fel d 7, present in small quantities in natural extracts), and serum albumin Fel d 2 (related to the cat-pork syndrome). IgA Fel d 5 and IgM Fel d 6 are not available as allergen components in the current commercial IgE immunoassays, but they may impair the in vitro diagnostic evaluation of cat allergy because galactose-α1,3-galactose is an IgE-binding epitope of these native feline allergens. The benefits of molecular-based cat allergy diagnosis are continually evaluated, as the role of recombinant allergen components already known is detailed and new other molecules of interest may be discovered in the future.
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Affiliation(s)
- Florin-Dan Popescu
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
| | - Carmen Saviana Ganea
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
| | - Carmen Panaitescu
- Department III Functional Sciences, Physiology Discipline, “Victor Babes” University of Medicine and Pharmacy, Timișoara 300041, Romania
- Center for Gene and Cell Therapies in Cancer Treatment OncoGen-SCJUPB Timisoara, Timișoara 300041, Romania
| | - Mariana Vieru
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
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Arroyo AC, Robinson LB, Geller RJ, Rudders SA, Sullivan AF, Hasegawa K, Camargo CA. Allergic sensitization during early life: Concordance between ImmunoCAP and ISAC results. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2021; 9:2126-2128.e3. [PMID: 33359588 PMCID: PMC8113067 DOI: 10.1016/j.jaip.2020.12.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 11/30/2020] [Accepted: 12/10/2020] [Indexed: 11/24/2022]
Affiliation(s)
- Anna Chen Arroyo
- Division of Pulmonary, Allergy & Critical Care Medicine, Stanford University School of Medicine, Stanford, Calif.
| | - Lacey B Robinson
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass; Harvard Medical School, Boston, Mass
| | - Ruth J Geller
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass
| | - Susan A Rudders
- Harvard Medical School, Boston, Mass; Division of Immunology, Boston Children's Hospital, Boston, Mass
| | - Ashley F Sullivan
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass
| | - Kohei Hasegawa
- Harvard Medical School, Boston, Mass; Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass
| | - Carlos A Camargo
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass; Harvard Medical School, Boston, Mass; Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass
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11
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Schoos AMM, Nwaru BI, Borres MP. Component-resolved diagnostics in pet allergy: Current perspectives and future directions. J Allergy Clin Immunol 2021; 147:1164-1173. [PMID: 33444632 DOI: 10.1016/j.jaci.2020.12.640] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/30/2020] [Accepted: 12/23/2020] [Indexed: 12/14/2022]
Abstract
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.
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Affiliation(s)
- Ann-Marie M Schoos
- COpenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Pediatrics, Slagelse Sygehus, Slagelse, Denmark.
| | - Bright I Nwaru
- Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Magnus P Borres
- Thermo Fisher Scientific, Uppsala, Sweden; Department of Maternal and Child Health, Uppsala University, Uppsala, Sweden
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12
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Ligabue-Braun R. Hello, kitty: could cat allergy be a form of intoxication? J Venom Anim Toxins Incl Trop Dis 2020; 26:e20200051. [PMID: 33456448 PMCID: PMC7781471 DOI: 10.1590/1678-9199-jvatitd-2020-0051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
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.
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Affiliation(s)
- Rodrigo Ligabue-Braun
- Department of Pharmacosciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
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13
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Gherasim A, Jacob A, Schoettel F, Domis N, de Blay F. Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC ® environmental exposure chamber. Clin Exp Allergy 2019; 50:160-169. [PMID: 31596983 DOI: 10.1111/cea.13511] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 09/20/2019] [Accepted: 09/25/2019] [Indexed: 01/01/2023]
Abstract
BACKGROUND Air cleaners have been promoted for respiratory allergic disease prevention, but there is no clear clinical proof of their efficacy in allergic asthma. OBJECTIVE To examine the efficacy of a new air cleaner on early and late asthmatic responses in cat-allergic patients. METHODS This randomized, cross-over, double-blind placebo-controlled study enrolled 24 cat-asthmatic patients with GINA 1 asthma. At baseline, participants were exposed to 40 ng/m3 of airborne cat allergen for a maximum of 2 hours in ALYATEC® environmental exposure chamber (EEC). All participants were subsequently randomized into two groups that were exposed to cat allergen, either with active then placebo air cleaners or with placebo then active air cleaners with a 3-week interval in the EEC. This study was registered under number (NCT03928561). RESULTS Fewer patients experienced an EAR with active air cleaners (seven patients; 29.17%) than placebo (21 patients; 87.50%). The response incidence was lower with active than with placebo air cleaners. A Cox model demonstrated a significant treatment effect (hazard ratio, 0.10; P = .002). Active air cleaners also prevented late asthmatic response: four patients (16.67%) had a late asthmatic response with active air cleaners compared to 11 patients (45.83%) with placebo (Prescott test P = .002). Active air cleaners also decreased the maximal severity of bronchial response (FEV1 decrease of 17.24% with active vs 25.62% with placebo air cleaners; P = .001). CONCLUSIONS Our present results demonstrated that Intense Pure Air XL® air cleaners significantly prevented early and late asthmatic responses among cat-allergic asthmatics during cat allergen exposure in the ALYATEC® EEC.
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Affiliation(s)
- Alina Gherasim
- ALYATEC® Environmental Exposure Chamber, 1 place de l'Hôpital, Strasbourg, France
| | - Audrey Jacob
- ALYATEC® Environmental Exposure Chamber, 1 place de l'Hôpital, Strasbourg, France
| | - Florian Schoettel
- ALYATEC® Environmental Exposure Chamber, 1 place de l'Hôpital, Strasbourg, France
| | - Nathalie Domis
- ALYATEC® Environmental Exposure Chamber, 1 place de l'Hôpital, Strasbourg, France
| | - Frederic de Blay
- ALYATEC® Environmental Exposure Chamber, 1 place de l'Hôpital, Strasbourg, France.,Chest Diseases Department, Strasbourg University Hospital, Strasbourg, France.,Federation of translational medicine EA 3070, University of Strasbourg, Strasbourg, France
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14
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Satyaraj E, Wedner HJ, Bousquet J. Keep the cat, change the care pathway: A transformational approach to managing Fel d 1, the major cat allergen. Allergy 2019; 74 Suppl 107:5-17. [PMID: 31498459 PMCID: PMC7156987 DOI: 10.1111/all.14013] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 08/01/2019] [Indexed: 12/22/2022]
Abstract
Background Allergies 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 Results This 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. Discussion The 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. Conclusion Efficacy 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.
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Affiliation(s)
| | - Harold James Wedner
- Division of Allergy and Immunology, Department of Medicine Washington University School of Medicine St. Louis MO USA
| | - Jean Bousquet
- University Hospital Montpellier France
- MACVIA‐France Fondation partenariale FMC VIA‐LR Montpellier France
- INSERM U 1168 VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches Villejuif France
- UMR‐S 1168 Université Versailles St‐Quentin‐en‐Yvelines Montigny le Bretonneux France
- Charité, Universitätsmedizin Berlin Humboldt‐Universität zu Berlin Berlin Germany
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15
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Satyaraj E, Li Q, Sun P, Sherrill S. Anti-Fel d1 immunoglobulin Y antibody-containing egg ingredient lowers allergen levels in cat saliva. J Feline Med Surg 2019; 21:875-881. [PMID: 31310154 PMCID: PMC6764009 DOI: 10.1177/1098612x19861218] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVES Fel d1 is the major cat allergen, causing IgE reactions in up to 90% of cat-allergic adults. Fel d1 secreted in saliva is spread to the haircoat during grooming. Current management includes attempts to reduce or eliminate exposure to Fel d1. A novel approach to reducing immunologically active Fel d1 (aFel d1) exposure, which involves binding the Fel d1 with an anti-Fel d1-specific polyclonal egg IgY antibody (sIgY), was evaluated. The hypothesis was that saliva from cats fed diets containing this sIgY would show a significant reduction in aFel d1. METHODS Two trials in cats were completed. In trial 1, saliva was collected 0, 1, 3 and 5 h post-feeding during a 2 week baseline and subsequent 6 week treatment period. Trial 2 included a control and treatment group, and saliva was collected once daily. Trial 2 cats were fed the control diet during a 1 week baseline period, and then fed either control or sIgY diet during the 4 week treatment period. Fel d1-specific ELISA was used to measure salivary aFel d1. Data were analysed using repeated-measures ANOVA and a linear mixed-model analysis. RESULTS Salivary aFel d1 decreased post-treatment in both trials. There were no differences in aFel d1 based on time of collection relative to feeding in trial 1. In trial 2, 82% of treatment group cats showed a decrease in aFel d1 of at least 20% from baseline vs just 38% of control cats. Only one (9%) treatment cat showed an increase in aFel d1 vs 63% of control cats. CONCLUSIONS AND RELEVANCE Feeding sIgY significantly reduced aFel d1 in the saliva of cats within 3 weeks. Although additional research is needed, these findings show promise for an alternative approach to the management of allergies to cats.
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Affiliation(s)
| | - Qinghong Li
- Research & Development, Nestlé Purina Research,
St Louis, MO, USA
| | - Peichuan Sun
- Research & Development, Nestlé Purina Research,
St Louis, MO, USA
| | - Scott Sherrill
- Research & Development, Nestlé Purina Research,
St Louis, MO, USA
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16
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Bastien BC, Gardner C, Satyaraj E. Influence of time and phenotype on salivary Fel d1 in domestic shorthair cats. J Feline Med Surg 2019; 21:867-874. [PMID: 31135257 PMCID: PMC6764004 DOI: 10.1177/1098612x19850973] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Objectives Fel d1 is a major allergen that may affect humans sensitive to cat allergens,
and it can be detected in the saliva and on the hair of cats. We studied the
variability of salivary Fel d1 in typical house cats (ie, neutered domestic
shorthair cats) and the factors that could be associated with that
variability. Methods Saliva samples were collected from 64 cats, twice daily, every other day, for
a year, at two locations (Missouri, USA, and Ontario, Canada). Salivary Fel
d1 levels were measured using an immunoassay. Correlations and linear
mixed-effects model analyses were run to assess which factors significantly
affected the Fel d1 levels. Results Salivary Fel d1 levels varied significantly both within and among cats. Cat
averages over the year ranged from 0.4–35 µg/ml, and a higher average
correlated with a higher SD (P <0.001). The first
collection of the day tended to be higher than the afternoon collection
(P <0.001). Sex, coat color or body size did not
relate to cats’ average Fel d1 production, but older cats tended to have
lower salivary Fel d1 levels (P <0.001). Fel d1 levels
from four samples were reliable in identifying cats producing stable low
levels of Fel d1. Conclusions and relevance We observed a wide and continuous range of salivary Fel d1 production in
domestic shorthair cats. In particular, a subset of cats had stable low
levels throughout the course of the year, and they can be identified by
analyzing a few saliva samples rather than their physical appearance.
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