Epithelial And Other Animal Allergens

The category of animal allergens includes animal emanations: hair, dander, feathers, saliva, and urine. Because domestic animals are widespread in our society and some of their emanations are potent allergens, the topic is important for the allergist. Occupational exposure of farmers, veterinarians, and laboratory workers has economic importance. Social and family interactions may be strained severely when one person becomes allergic to a beloved family pet. The allergist often is called on to solve these problems.

Hair itself is not an important allergen because it is not buoyant or water soluble. Water-soluble proteins of epidermal or salivary origin that are attached to the hair are important allergens, however. Dander is a term used to describe desquamated epithelium. Desquamation is a continuous process for all animals, and the dander materials contain many water-soluble proteins that are highly antigenic and allergenic. Saliva also is rich in proteins such as secretory IgA and enzymes. People commonly develop local urticaria at the sites where they have been licked by a cat or dog or where they have been scratched by claws or teeth. Rodents excrete significant amounts of allergenic protein in their urine. All of these substances become part of the amorphous particulate matter of the air and are responsible for allergic morbidity.

Cats seemingly produce the most dramatic symptoms in sensitive individuals, particularly in those who are exposed intermittently. Whether this is caused by the concentration of cat allergens in the environs or by the potency of the allergens is unknown. Studies with cat pelts have disclosed a substance called Fel d 1 that appears to be the major allergen, recognized by over 80% of cat-sensitive individuals (195). Fel d 1 is produced mainly in cat saliva, but is also in the sebaceous glands of the skin, the sublingual glands, and even in the brain ( 196,197). The Fel d 1 molecule has been cloned. There is still controversy over the biologic activity of Fel d 1.

Fel d 1 may be detected in the urine of male cats but not of female cats. Allergens other than Fel d 1 in some sensitive individuals also have been detected in cat serum and urine, but these are minor allergens (198). Studies with individual cats show that some cats are high producers of allergen and others are not. Moreover, the rate of allergen production of individual cats varies from hour to hour. Male cats generally produce greater amounts of allergen than females. These factors may explain why some patients are more allergic to certain cats than to others (196). In addition, there does not appear to be any seasonal variation in Fel d 1 production.

Air sampling in rooms occupied by cats has shown that the amount of Fel d 1 allergen required to cause a 20% decrease in forced expiratory volume in 1 second (FEV.|) on pulmonary function testing is comparable with the amounts required in conventional bronchoprovocation testings (approximately 0.09 pg/mL). Morphologic room sampling shows abundant squamous cell fragments smaller than 5 pm, enabling these fragments to reach small bronchioles and alveoli (199). This small particle size also explains why cat allergen can remain airborne in undisturbed conditions for extended periods.

Serial dust samples collected in the study of 15 homes after removal of the family cats were analyzed for Fel d 1. Baseline amounts of antigen ranged from 8 to 437 FDA units/gram of dust (median, 61 U/g). After removing the cats, the levels decreased to those of control homes in 20 to 24 weeks. However, significant differences occurred in the rate of decline of Fel d 1 among homes. It may therefore be prudent to advise patients that it might take up to 6 months after removal of a cat for the bulk of the cat allergens to disappear from the home (200).

Dog allergens have been identified in dander, saliva, urine, and serum, but elegant studies like the ones described for cats have not been published. The major dog allergen, Can f 1, has been described and can be assayed, although most skin tests and RASTs use dander as the basis of diagnosing allergy to dogs. Using RAST inhibition, dog sera had little effect on the binding of dog dander ( 201). In the same experiments, using dander from 13 breeds of dogs and sera of 16 patients with documented dog allergy, the various sera showed significant breed specificity. Dander from all breeds was allergenic, including poodle. However, differences between breeds occur in the number and amount of antigens. More recently Can f 1 and Can f 2 have been cloned and described as lipocalins, small ligand binding proteins (202). About 30% of dog allergic patients show IgE reactivity to albumin. These patients have a high cross-reactivity with cat and other animal albumins ( 2.03). There is individual variation in the positivity of skin test results to different breeds, but in one study these variations did not correlate with the patient's perception of specific breed allergy (204). The fact that dogs tend to spend more time outdoors and are bathed more frequently may explain their decreased importance as an allergen source relative to cats.

Most patients who are demonstrably sensitive to dander are also sensitive to other perennial allergens. This complicates the determination of which allergen is responsible for their symptoms. The recommendation to eliminate a pet from a home environment places the clinician in a difficult position. Patients do not readily accept the proposition that their pet may be the cause of their allergic problem, even in light of positive skin test results. Positive bronchial provocation might be supportive, but results are not conclusive. Cat allergen is known to persist in the home for up to 24 weeks after removal of the pet, so a trial separation of the patient away from the home environment for several weeks to months is probably the best prognostic indicator at this time.

Horses resemble cats in the explosive symptoms that may occur on exposure to their dander, but this clinical situation is less common and less difficult to manage, primarily because of the absence of horse dander in the home. Horse hair has been used in the manufacture of some mattresses, furniture, and rug pads, but again, the allergic potential of hair does not approach that of dander. Some antigens are common to horse dander and serum, creating the potential for a serious problem in patients when horse serum (such as an antivenom) may be urgently needed. Tetanus antitoxin currently is available as a human antiserum. Two horse allergens have been identified so far. Equ c 1 and Equ c 2 have been cloned and both described as members of the lipocalin family (205,206).

Allergy to cows, goats, and sheep usually is occupational. Rabbits and small rodents such as gerbils, hamsters, guinea pigs, rats, and mice are common household pets, and their dander may induce severe reactions on skin prick testing. Significant skin test reactivity to the dander of rats and mice in persons whose homes are infested with these rodents also may be seen.

Allergic symptoms in laboratory workers exposed to immune allergens have promoted several studies on the nature of these allergens ( 207,208). In mouse-sensitive subjects, a major urinary protein, Mus m 1, appears to be the primary allergen. It is the most prominent member of a family of allergenic murine proteins collectively known as the major urinary proteins (209). The major urinary proteins are also lipocalins and have sequence homology with Can f 2 (202). Mus m 1 protein is synthesized in the liver, and its synthesis is stimulated by androgen, accounting for fourfold higher concentrations in male mice than in females. The urine from both sexes of mice contains 10 times more of this allergen than does the serum. Mus m 1 is also formed in the sebaceous, parotid, and lacrimal glands, which probably explains the small quantities detected in pelt extract. The potency of this allergen in susceptible individuals was illustrated by the finding that intermittent exposure to these allergens of at least 10 days a year produced the same level of allergy in terms of IgE-related tests as daily exposure ( 207).

Rats and other small mammals commonly produce respiratory symptoms in laboratory workers. The airborne level of rat allergens can be high—up to 100 pg/m 3 Furthermore, urinary allergens are carried in small particles about 7 pm in diameter. Workers with intense exposure to rats develop IgG antibodies to rat urinary protein, but in the absence of IgE to these proteins, these subjects are asymptomatic. The presence of IgE antibodies to rat urinary proteins in laboratory workers usually is associated with asthma or rhinitis. Both atopic and nonatopic individuals are able to make the specific IgE ( 210). The two predominant rat urinary allergens are termed Rat n 1 and Rat n 2. Air sampling techniques for rat allergens have reported that feeding and cleaning produce the highest airborne concentrations of the prealbumin protein Rat n 1 (21 ng/m3), injection and handling produce exposure to somewhat less allergen, and surgery and killing rats produce only 3.4 ng/m 3 Low concentrations of rat allergens were found outside of the handling rooms (211). Of the three layers of rat pelt, the outermost fur was most allergenic, probably because of contamination with body fluids. In one study, rat sebaceous glands were not found to be the source of allergenic secretions ( 212), but other studies have reported a high-molecular-weight protein (over 200 kDa), which was believed to originate from rat sebaceous glands ( 213). Rat n 2 has been definitively demonstrated in the liver, lacrimal, and salivary glands (21.4).

The question has been raised whether laboratory workers who deal with allergenic rodents should be screened for atopy before employment. Although it was thought initially that workers with seasonal allergic rhinitis are more likely to become allergic to laboratory animals ( 215), more recent studies conclude that such screening is not warranted because nonatopic individuals may become allergic when exposed to sufficient allergen loads ( 210,216). Of course a screening test for existing specific animal allergens may be useful, particularly if the worker has a choice of working with different animal species.

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