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Whole Allergen

e75 Rat serum proteins

e75 Rat serum proteins Scientific Information

Type:

Whole Allergen

Display Name:

Rat serum proteins

Family:

Muridae

Latin Name:

Rattus norvegicus

Other Names:

Rat, Brown rat, House rat, Norway rat

Route of Exposure

This species of Rat is not a native of Norway, as its name suggests. The species originated in Asia, reached Europe early in the eighteenth century and arrived in North America about 1775 on ships from England. Its distribution is now worldwide.

Many consider this Rat to be the greatest mammal pest of all time. It has caused more deaths than all the wars in history. It harbours lice and fleas and has been the source of bubonic plague, typhus, trichina, tularemia, infectious jaundice and other serious diseases. These Rats are usually a contributing factor of first importance in the spread of pandemics during war. They also cause considerable depletion and pollution of human food stores, and damage to buildings and their contents from destructive chewing of wiring, pipes, and walls. But despite human efforts to exterminate Rats, the House Rat population is probably equal to the human population.

The Brown Rat grows up to 25cm long excluding the naked, scaly tail, and sometimes weighs more than half a kilogram. It is commonly brown with whitish underparts and pink ears, feet, and tail. It breeds, and therefore aggressively forages, all year round.

As small, intelligent, bold, prolifically breeding omnivores, nesting in practically any sort of disused cavity or burrowing in the ground, and adept at swimming, jumping and climbing, Brown Rats are highly adaptable and live in a great variety of environments. They may hide in huge numbers in and around human dwellings, especially in cities, towns and their surroundings, There, they live principally in basements, on the ground floor, in subways, and in burrows under sidewalks or outbuildings. They are also frequently found in cultivated fields, grain storage facilities, livestock housing and garbage dumps. Basically, they are at home wherever there is a food source and sufficient cover from predators, and this includes some unexpected places like the salt marshes of the US Atlantic coast, where edible flotsam is washed up on the beaches.

Especially because of the numbers of Rats used in laboratories, allergy to Rats is an important occupational health problem.

Clinical Relevance

Allergen description

n serum, 75 kDa and 68 kDa serum protein allergens have been isolated, the former probably serum albumin and the latter probably transferrin. These proteins are also present in Rat urine (1). The prevalence of specific IgE in Rat-allergic patients to the 68 kDa (albumin) allergen is between 24% and 28.9% (2-4).

The number of Rats, Rats' bedding, cage design, and stock density influence the level of aeroallergen concentration and exposure (5). Rat allergen can also be carried on clothes or by wind to distant sites, with traces of Rat urinary aeroallergens measured in tea rooms inside and near offices outside the animal housing (6-7).

The highest airborne Mouse allergen levels have been measured during manual emptying of cages, during changing of cages on an unventilated table, and during handling of male animals on an unventilated table. Using ventilated cage-changing wagons has been shown to reduce the allergen exposure level from 77 to 17 ng/m3 (8). Similar results can be expected with Rats. Airborne Rat allergens are particles ranging from 1 to 20 micrometres in size, and can remain airborne for 60 minutes or more after disturbance. Rat allergen exposure levels less than 0.7 microg/m3 appear not to be associated with an increased risk of occupational asthma (9). More intense exposure to airborne Rat n 1 and endotoxin occurs not only during cleaning, but also during feeding tasks, probably because the allergens become airborne during the disturbance (10).

Rat dust is a complex allergenic source and contains allergens from Rats' urine (containing serum proteins), epithelium and saliva (11).

Potential Cross Reactivity

In IgE immunoblot inhibition studies and histamine release tests, it has been demonstrated that patients who react to Dog albumin exhibit IgE reactivity with purified albumins from Cat, Mouse, Chicken, and Rat. Significant sequence homologies have been demonstrated with albumins from different species: Human: 82.6%, Pig: 81.8%, Cattle: 77.3%, Sheep: 78.8%, Mouse: 75.8%, and Rat: 76.2% (12).

Practically all respiratory animal allergens, including Rat, characterised at the molecular level belong to the lipocalin family of proteins. Examples are the major allergens of Horse, Cow, Dog, Mouse and Cockroach as well as beta-lactoglobulin of Cow's milk (13). A certain degree of cross-reactivity is thus possible.

Molecular Aspects

Clinical Experience

IgE mediated reactions

Rat allergens found in dust, urine (containing serum proteins), epithelium and saliva are a frequent cause of asthma, allergic rhinitis and allergic conjunctivitis, mainly in laboratory workers but also in ordinary individuals (14-16).

There is a strong association between work-related symptoms and specific sensitisation (17). Workers exposed to laboratory animals are at risk of developing asthma, rhinitis, angioedema, conjunctivitis, and urticaria. Between 10% and 33% of scientists and technicians handling small animals will develop laboratory animal allergy symptoms within 3 years of employment. Many of them will have severe symptoms requiring a change of occupation (11, 18-20).

In workers exposed to Rats, Rat urinary allergen sensitisation risk increased with increasing exposure intensity. Workers who were atopic had a clearly elevated sensitisation risk at low allergen exposure levels (21). In a cross-sectional study performed on 540 workers at 8 facilities to quantify the exposure-response relationship for allergy to Rats, no clear exposure-response relationship was observed. However, in the group of workers with less than 4 years of working experience with laboratory animals, the prevalence rate of sensitisation to Rat allergens was clearly associated with exposure levels. The exposure-response relationship was steepest for workers with atopy-associated risk factors, i.e., self-reported allergy or sensitisation to Cats or Dogs, or elevated total serum IgE. The prevalence rates of sensitisation to Rat allergens for these workers were about 15, 9.5, and 7.3 times higher in the high-, medium-, and low-exposure group, respectively, compared with the internal reference group (22).

A large epidemiological study of 5,000 laboratory workers reported symptoms in 26% exposed to Mice, 25% to Rats, 31% to Guinea Pigs, 30% to Rabbits, 26% to Hamsters, 25% to Dogs, 30% to Cats and 24% to Monkeys (23).

Two hundred and sixty-three United Arab Emirates nationals with a respiratory disease suspected of being of allergic origin were submitted to skin- and serum-specific IgE measurement. Of these individuals, 8.3% were sensitised to Cat fur, 4.9% to Goat hair, and 0.7% to Rat hair and Mouse hair (24).

The suitability of radioallergosorbent test (RAST) inhibition to quantify occupational exposure to Rat urinary aeroallergen (RUA) has been assessed. The authors conclude that, in view of the complexity of Rat allergens, RAST inhibition is an appropriate method for the quantification of occupational exposure to Rats (25).

Compiled By

Last reviewed: June 2022.

References
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  2. Gordon S, Tee RD, Newman Taylor AJ. Analysis of rat urine proteins and allergens by sodium dodecylsulfate-polyacrylamide gel eletrophoresis and immunoblotting. J Allergy Clin Immunol 1993;92:298-305
  3. Wahn U, Peters T, Siraganian RP. Studies on the allergenic significance and structure of rat serum albumin. J Immunol 1980;125:2544-9
  4. Wood RA. Laboratory animal allergens. ILAR J 2001;42(1):12-6
  5. Taylor AJ, Gordon S, Tee RD. Influence of bedding, cage design, and stock density on rat urinary aeroallergen levels. Am J Ind Med 1994;25(1):89
  6. Nieuwenhuijsen MJ, Gordon S, Tee RD, Venables KM, McDonald JC, Newman Taylor AJ. Exposure to dust and rat urinary aeroallergens in research establishments. Occup Environ Med 1994;51(9):593-6
  7. Gordon S, Tee RD, Lowson D, Wallace J, Newman Taylor AJ. Reduction of airborne allergenic urinary proteins from laboratory rats. Br J Ind Med 1992;49(6):416-22
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  11. Gordon S, Tee RD, Newman Taylor AJ. Analysis of the allergenic composition of rat dust. Clin Exp Allergy 1996;26(5):533-41
  12. Spitzauer S, Schweiger C, Sperr WR, Pandjaitan B, Valent P, Muhl S, Ebner C, Scheiner O, Kraft D, Rumpold H, et al. Molecular characterization of dog albumin as a cross-reactive allergen. J Allergy Clin Immunol 1994;93(3):614-27
  13. Mantyjarvi R, Rautiainen J, Virtanen T. Lipocalins as allergens. Biochim Biophys Acta 2000;1482(1-2):308-17
  14. Moller NE, Wurden KV. Allergy to laboratory rats. [Danish] Ugeskr Laeger 1984;146(49):3869-72
  15. Hunskaar S, Fosse RT. Allergy to laboratory mice and rats: a review of the pathophysiology, epidemiology and clinical aspects. Lab Anim 1990;24(4):358-74
  16. Platts-Mills TA, Longbottom J, Edwards J, Heymann PW. Asthma and rhinitis related to laboratory rats: use of a purified rat urinary allergen to study exposure in laboratories and the human immune response. N Engl Reg Allergy Proc 1987;8(4):245-51
  17. Cullinan P, Lowson D, Nieuwenhuijsen MJ, Gordon S, Tee RD, Venables KM, McDonald JC, Newman Taylor AJ. Work related symptoms, sensitisation, and estimated exposure in workers not previously exposed to laboratory rats. Occup Environ Med 1994;51(9):589-92
  18. Hunskar S. Allergy to laboratory animals. A new problem of the occupational environment. [Norwegian] Tidsskr Nor Laegeforen 1989;109(24):2453-5
  19. Hollander A, Heederik D, Brunekreef B. Work-related changes in peak expiratory flow among laboratory animal workers. Eur Respir J 1998;11(4):929-36
  20. Hesford JD, Platts-Mills TA, Edlich RF. Anaphylaxis after laboratory rat bite: an occupational hazard. J Emerg Med 1995;13(6):765-8
  21. Heederik D, Venables KM, Malmberg P, Hollander A, Karlsson AS, Renstrom A, Doekes G, Nieuwenhijsen M, Gordon S. Exposure-response relationships for work-related sensitization in workers exposed to rat urinary allergens: results from a pooled study. J Allergy Clin Immunol 1999;103(4):678-84
  22. Hollander A, Heederik D, Doekes G. Respiratory allergy to rats: exposure-response relationships in laboratory animal workers. Am J Respir Crit Care Med 1997;155(2):562-7
  23. Aoyama K, Ueda A, Manda F, Matsushita T, Ueda T, Yamauchi C. Allergy to laboratory animals: an epidemiological study. Br J Ind Med 1992;49(1):41-7
  24. Lestringant GG, Bener A, Frossard PM, Abdulkhalik S, Bouix G. A clinical study of airborne allergens in the United Arab Emirates. Allerg Immunol (Paris) 1999;31(8):263-7
  25. Gordon S, Tee RD, Nieuwenhuijsen MJ, Lowson D, Harris J, Newman Taylor AJ. Measurement of airborne rat urinary allergen in an epidemiological study. Clin Exp Allergy 1994;24(11):1070-7