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Cat dander

e94 Fel d 1

Allergen Component
Biological Function Uteroglobin
Code e94
Allergome Code 345
LOINC 64975-6
Main route of exposure Airway (Inhalation)
Source Material Epidermis, fur
Latin Name Felis domesticus
Other Names Cat I, Ag4, Fel d 1-related protein
Categories Epidermal and Animal Proteins

Summary

Fel d 1 is the most important and major cat allergen as it has been observed in up to 95% of individuals with cat allergy. Sixty to 90% of all IgE reactivity to cat dander is against the Fel d 1. The primary production of Fel d 1 takes place in sebaceous, anal, and salivary glands and its highest concentration can be found in the fur and epidermis of a cat. Fel d 1 becomes airborne very easily and then is carried by small particles, which in turn transfers it to environments that have not had any exposure to a cat.

Fel d 1 is a uteroglobin, but the biological role remains a mystery.  The allergenicity of inhaled Fel d 1 increases after it manages to bind the mannose receptors present on dendritic cells. This binding initiates the production of IgE and IgG1 specific to Fel d 1.

Higher levels of IgE specific to Fel d 1 have been seen in cat allergic children with allergic asthma as compared to those only with rhinitis. This indicates that an increased asthma risk could be predicted by high levels of IgE antibodies to Fel d 1. (1)

Epidemiology

Worldwide distribution

Fel d 1 is the major feline allergen, it is mainly a component in cat dander and dominates the IgE response in patients with cat allergy. Cat allergic patients with IgE to Fel d 1 have also reacted to different species of the Felidae family, such as puma, Siberian tiger, lion, jaguar, and snow leopard. (2) 

Environmental Characteristics

Source and tissue

It has been documented that Fel d 1 becomes airborne very easily and then is carried by small particles, which in turn transfers it to environments that have not had any exposure to a cat. The concentration in such environments has been at levels that exceed the proposed sensitization threshold of 8 µg/gm. (3-6)

Risk factors

A study by Bjerg and colleagues on 696 Swedish children reported that current asthma and symptoms of asthma after contact with cats were linked to co-sensitization to Fel d 1 and Fel d 4. (7)

Clinical Relevance

Allergic rhinitis and Asthma

The increment of Fel d 1 IgE levels could be a significant risk factor for allergic asthma in children. A study demonstrated Fel d 1 strong association with the prevalence, severity, and persistence of asthma in a 19-year-old population. Furthermore, in a study where patients were sensitized to cat extract and components, the ones sensitized to components were more likely to develop asthma and rhinitis.  (3).

Gronlund and colleagues did a case-control study on 140 cat allergic patients from Austria and Sweden, in which all subjects were suffering from asthma and/or rhinoconjunctivitis. They observed that 95.6% of children and 94.4% of adults had IgE against Fel d 1. The IgE levels were found in asthmatic children were significantly higher than the ones of children suffering from rhinoconjunctivitis. (3)

 

Prevention and Therapy

Allergen immunotherapy

Fel d 1 IgE have shown to have a similar or slightly lower sensitivity for positive diagnosis and it is correlated with the severity and risk of asthma occurrence and could be a good prospect for immunotherapy in years to come. (3)

Molecular Aspects

Biochemistry

The molecular weight of Fel d 1 is 36 kDa (9). It is a dimer of a polypeptide comprised of two chains 1 and 2 (also known as α and β), chain 1 consists of 70 and chain 2 is made up of 92 amino acid residues. They have conformational IgE binding epitopes independent of carbohydrate residues even though N- terminal oligosaccharides are present on chain 2. It is an uteroglobulin , previously called secretoglobulin.

Studies conducted on recombinantly synthesized chain 1 and 2 have shown that IgE binding epitopes are present on both chains and both the chains contribute to the allergenicity of Fel d 1.

Isoforms, epitopes, antibodies

Two mammalian allergens have been characterized as members of uteroglobin(part of secretoglobulin superfamily) protein family, namely Fel d 1 from cat and Ory c 3 from rabbit. (8) Ory c 3, the major rabbit allergen is a lipophilin and found to be a Fel d 1-like molecule. However, the sequence identity between the two allergens is very low and no IgE cross-reactivity has been observed between them. (9)

Cross-reactivity

No major cross-reactivity to Fel d 1 has been reported. (1)

Diagnostic Relevance

Disease Severity

It has been observed that individuals sensitized to cat components have a higher risk of developing asthma than the individuals sensitized only to cat extract, this risk becomes even higher in children. (3)

A review by Bonnet and colleagues in 2018 suggests that measuring IgE antibodies to Fel d 1 makes it possible to better estimate the prognosis of cat allergy and evaluate the severity of cat allergy. (3)

Exposure

As the major cat protein Fel d 1 is a “sticky” allergen, it can take several months after the removal of the cat to alleviate the allergic symptoms particularly in carpeted households. (10, 11). It has been observed that Fel d 1 levels are reduced after up to 20 weeks after the removal of the cat. (11)

Compiled By

Reviewer: Dr. Christian Fischer

Last reviewed: November 2020 

References
  1. Konradsen JR, Fujisawa T, Van Hage M, Hedlin G, Hilger C, Kleine-Tebbe J, et al. Allergy to furry animals: New insights, diagnostic approaches, and challenges. Journal of Allergy and Clinical Immunology. 2015;135(3):616-25.
  2. de Groot H, van Swieten P, Aalberse RC. Evidence for a Fel d I-like molecule in the "big cats" (Felidae species). J Allergy Clin Immunol. 1990;86(1):107-16.
  3. Bonnet B, Messaoudi K, Jacomet F, Michaud E, Fauquert JL, Caillaud D, et al. An update on molecular cat allergens: Fel d 1 and what else? Chapter 1: Fel d 1, the major cat allergen. Allergy Asthma Clin Immunol. 2018;14:14.
  4. Chen CM, Thiering E, Zock JP, Villani S, Olivieri M, Modig L, et al. Is there a threshold concentration of cat allergen exposure on respiratory symptoms in adults? PLoS One. 2015;10(6):e0127457.
  5. 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(S107):5-17.
  6. Zahradnik E, Raulf M. Respiratory Allergens from Furred Mammals: Environmental and Occupational Exposure. Vet Sci. 2017;4(3).
  7. Bjerg A, Winberg A, Berthold M, Mattsson L, Borres MP, Ronmark E. A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren. Pediatr Allergy Immunol. 2015;26(6):557-63.
  8. Hilger C, Van Hage M, Kuehn A. Diagnosis of Allergy to Mammals and Fish: Cross-Reactive vs. Specific Markers. Current Allergy and Asthma Reports. 2017;17(9).
  9. Hilger C, Kler S, Arumugam K, Revets D, Muller CP, Charpentier C, et al. Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen. J Allergy Clin Immunol. 2014;133(3):759-66.
  10. Warner JO. Use of temperature-controlled laminar airflow in the management of atopic asthma: clinical evidence and experience. Therapeutic Advances in Respiratory Disease. 2017;11(4):181-8.
  11. Wood RA, Chapman MD, Adkinson NF, Eggleston PA. The effect of cat removal on allergen content in household-dust samples. 1989;83(4):730-4.