1
|
Cleveland CW, Davis BW, Khatri K, Pomés A, Chapman MD, Brackett NF. Genetic diversity of the major cat allergen, Fel d 1. PNAS NEXUS 2024; 3:pgae447. [PMID: 39600803 PMCID: PMC11577610 DOI: 10.1093/pnasnexus/pgae447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 09/27/2024] [Indexed: 11/29/2024]
Abstract
Cat allergy affects ∼15% of the US population and can cause severe symptoms, including asthma. The major cat allergen, Fel d 1, drives IgE antibody responses. We conducted a comparative analysis of Fel d 1 genes, CH1 and CH2, and investigated structural features of Fel d 1 homologs across the family Felidae. The CH1 and CH2 domestic cat DNA references were used to identify homologous sequences in domestic and exotic cat genomes. Variability of these sequences within or across cat species was analyzed. Comprehensive alignments of Fel d 1 sequences and homologs from 276 domestic or exotic cats identified >100 unique, dissimilar substitutions in the protein sequences across Felidae. Selective pressure analyses of 37 exotic cat species revealed that Fel d 1 experienced positive selection, or greater variability over time, in CH1 and CH2. Linear regression of the mean pairwise identities of Fel d 1 DNA or protein sequences indicated that the genes largely reflected the evolution of Felidae. The Fel d 1 genes are highly variable (41 and 58% of the amino acid residues encoded by CH1 and CH2, respectively), suggesting that the biological function of Fel d 1, which is currently unknown, may vary among cat species and/or that Fel d 1 may be nonessential for cats. This is supported by Fel d 1 homology to nonessential proteins and recent evidence of healthy cats with CRISPR-edited CH2 genes. Fel d 1 variability could confer an evolutionary advantage for cats by allowing the allergen to bind different physiological ligands.
Collapse
Affiliation(s)
| | - Brian W Davis
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA
| | - Kriti Khatri
- Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA
| | - Anna Pomés
- InBio, Charlottesville, 700 Harris St, VA 22903, USA
| | | | | |
Collapse
|
2
|
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.
Collapse
Affiliation(s)
- Maike Schroers
- Clinic of Small Animal Surgery and Reproduction, Veterinary Faculty, Ludwig-Maximilians-University Munich, Munich, Germany
| | | |
Collapse
|
3
|
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.
Collapse
|
4
|
Liguori G, Costagliola A, Lombardi R, Paciello O, Giordano A. Human-Animal Interaction in Animal-Assisted Interventions (AAI)s: Zoonosis Risks, Benefits, and Future Directions-A One Health Approach. Animals (Basel) 2023; 13:1592. [PMID: 37238022 PMCID: PMC10215372 DOI: 10.3390/ani13101592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/01/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Animal-assisted interventions (AAI)s represent the expression of integrated medicine, according to the One Health approach. Actually, animal-assisted therapies and animal-assisted activities are implemented in hospitals, rehabilitation centers, etc. The efficacy of AAIs is based on interspecific interactions and would be impacted by different factors, such as the characters of both the animal and the handler, a suitable selection of animal species, an appropriate animal educational protocol, the relationship between the handler and the animal, and mutual relationship among the animal, the patients, and members of the working team. AAIs produce many advantages for the patients but could expose them to zoonotic-pathogens transmission. Therefore, positive animal welfare, as preventative medicine to avoid incidents or transmission of zoonosis, is a relevant aspect with implications for human and animal health and wellbeing. This review aims to summarize the current published knowledge regarding the occurrence of pathogens in AAIs and to discuss their relevance in light of health and safety in AAIs participants. In addition, this review will contribute to defining the state of the art of AAIs through a careful benefits/challenges analysis and offers discussion points on the possible future developments according to the One Health approach.
Collapse
Affiliation(s)
- Giovanna Liguori
- Department of Veterinary Medicine and Animal Productions, University of Napoli Federico II, 80138 Napoli, Italy; (G.L.); (O.P.)
- Local Health Authority, ASL Foggia, 71122 Foggia, Italy;
| | - Anna Costagliola
- Department of Veterinary Medicine and Animal Productions, University of Napoli Federico II, 80138 Napoli, Italy; (G.L.); (O.P.)
| | | | - Orlando Paciello
- Department of Veterinary Medicine and Animal Productions, University of Napoli Federico II, 80138 Napoli, Italy; (G.L.); (O.P.)
| | - Antonio Giordano
- Sbarro Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA;
- Department of Medical Biotechnology, University of Siena, 53100 Siena, Italy
| |
Collapse
|
5
|
Brackett NF, Davis BW, Adli M, Pomés A, Chapman MD. Evolutionary Biology and Gene Editing of Cat Allergen, Fel d 1. CRISPR J 2022; 5:213-223. [PMID: 35343817 DOI: 10.1089/crispr.2021.0101] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Allergy to domestic cat affects up to 15% of the population, and sensitization to cat allergen is associated with asthma. Despite the pervasiveness of cat allergic disease, current treatments have limited impact. Here, we present a bioinformatics analysis of the major cat allergen, Fel d 1, and demonstrate proof of principle for CRISPR gene editing of the allergen. Sequence and structural analyses of Fel d 1 from 50 domestic cats identified conserved coding regions in genes CH1 and CH2 suitable for CRISPR editing. Comparative analyses of Fel d 1 and orthologous sequences from eight exotic felid species determined relatively low-sequence identities for CH1 and CH2, and implied that the allergen may be nonessential for cats, given the apparent lack of evolutionary conservation. In vitro knockouts of domestic cat Fel d 1 using CRISPR-Cas9 yielded editing efficiencies of up to 55% and found no evidence of editing at predicted potential off-target sites. Taken together, our data indicate that Fel d 1 is both a rational and viable candidate for gene deletion, which may profoundly benefit cat allergy sufferers by removing the major allergen at the source.
Collapse
Affiliation(s)
| | - Brian W Davis
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| | - Mazhar Adli
- Robert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | | | | |
Collapse
|
6
|
Abstract
PRACTICAL RELEVANCE Human allergy to cats affects a substantial and growing proportion of the global population, and cat allergy is regarded as the third most common cause of human respiratory allergies, and the second most common indoor cause. Veterinarians will frequently encounter owners who are cat-allergic, and having an understanding of this disease and the methods available to help control the allergy will assist them in giving appropriate advice, alongside human healthcare professionals. AIM The aim of this review is to summarise currently available data on the prevalence, causes, symptoms and control of human allergy to cats. In terms of managing cat allergy, the emphasis is on reviewing current and emerging modalities to reduce environmental exposure to cat allergens rather than on pharmacotherapy or immunotherapy, as it is in these areas in particular that the veterinarian may be able to offer help and advice to complement that of human healthcare professionals. EVIDENCE BASE The information in this review is drawn from the current and historical literature on human allergy to cats, and approaches to reduce exposure to cat allergens and manage symptoms of cat allergy.
Collapse
|
7
|
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.
Collapse
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
| |
Collapse
|
8
|
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.
Collapse
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
| |
Collapse
|
9
|
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.
Collapse
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
| |
Collapse
|
10
|
Satyaraj E, Gardner C, Filipi I, Cramer K, Sherrill S. Reduction of active Fel d1 from cats using an antiFel d1 egg IgY antibody. Immun Inflamm Dis 2019; 7:68-73. [PMID: 30851084 PMCID: PMC6485700 DOI: 10.1002/iid3.244] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 02/07/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Fel d1 is the most important allergen from cats. Fel d1 is produced primarily in saliva and spread to the haircoat during grooming and then transferred to the environment via hair and dander. OBJECTIVES A novel approach to reducing allergenic Fel d1 exposure was evaluated, involving binding the Fel d1 with an anti-Fel d1 polyclonal egg IgY antibody. The hypothesis was that hair from cats who had been fed foods containing anti-Fel d1 IgY would show a significant reduction in active Fel d1 (aFel d1). METHODS Hair collected from 105 cats completing a 12-week study was evaluated for aFel d1 via ELISA. Hair was collected four times over a 2-week baseline period, then weekly during the 10 week treatment period during which cats consumed a food containing the anti-Fel d1 IgY. RESULTS Baseline aFel d1 (μg/g hair) varied greatly among the cats in this study. From week 3, there was a significant reduction in mean aFel d1 with an overall average decrease of 47% by week 10, ranging from a 33-71% decrease vs baseline. Cats with the highest baseline aFel d1 showed the greatest decrease in aFel d1. CONCLUSIONS & CLINICAL IMPLICATIONS Feeding anti-Fel d1 IgY to cats successfully reduced aFel d1 on their haircoat with the greatest decreases observed in cats with initially high levels. Feeding a diet with anti Fel d1 IgY significantly reduced the active Fel d1 on the hair of cats.
Collapse
|