Focus on cat allergen (Fel d 1): immunological and aerodynamic characteristics, modality of airway sensitization and avoidance strategies

The increasing frequency of pet ownership (especially cats) in many industrialized countries has raised the level of exposure to the allergens produced by these animals. Moreover, it is likely that modern energy-saving systems and the wide use of upholstered furniture has resulted in closer contact between cats (and their allergens) and humans. Many different methods have been developed to quantify the main cat allergen (Fel d 1) in settled dust and in ambient air. The threshold levels of cat allergen inducing sensitization or triggering respiratory symptoms in sensitized patients have been calculated in settled dust, but airborne amounts of Fel d 1 probably represent a more reliable index of allergen exposure. Noticeably, the amount of Fel d 1 may be relatively high also in confined environments where cats have never been kept. It has been demonstrated that clothes of cat owners are the main source for dispersal of allergens in cat-free environments. This fact may be of relevance, because recent studies have shown that allergic sensitization to cats is more likely to develop in children exposed to moderate levels of this allergen than in children exposed to high amounts of Fel d 1. The ubiquity of cat allergen may justify the common observation that allergen avoidance is often insufficient to reduce the risk of developing allergic sensitization and/or symptom exacerbation in highly susceptible patients. Further efforts are needed to improve the efficacy of Fel d 1 avoidance strategies to try to reduce the risk of allergic sensitization to this allergen.     

Cat and dust mite sensitivity and tolerance in relation to wheezing among children raised with high exposure to both allergens

BACKGROUND: Recent evidence has suggested that high exposure to cat allergens is associated with decreased prevalence of sensitization to cat and, in some studies, decreased asthma. OBJECTIVE: Our objective was to study antibodies to cat and mite allergens and their relationship to wheezing in a country with high exposure to both allergens. METHODS: Sera from 112 wheezing and 112 control children aged 10 to 11 years in a nested case-control study in New Zealand were assayed for specific IgE antibody, as well as IgG antibody and IgG4 antibody, to Der p 1 and Fel d 1. RESULTS: IgE antibody to both mite (99/224) and cat (41/224) were strongly associated with wheezing (odds ratios, 5.2 and 6.5, respectively). Children who had ever lived with a cat were less likely to have IgE antibody to cat (20/141 vs 21/83, P < .04); however, cat ownership had no effect on IgE antibody to mite (67/141 vs 32/83, P = .23). Among sensitized children, cat ownership was associated with a lower prevalence of IgE antibody to cat (28% vs 66%, P < .001), and this analysis remained significant after exclusion of children whose families had chosen not to own a cat. Among sensitized subjects, the mean titer of IgE antibody to cat (1.7 IU/mL) was 10-fold lower than for mite (22.1 IU/mL). A cat in the home had no significant effect on endotoxin or mite allergen in house dust, whereas cat allergen was much higher (40.8 vs 3.3 microg/g). CONCLUSION: The response to these 2 allergens was distinct on the basis of the prevalence of sensitization, the titer of IgE antibody, and the effect of cat ownership. The results suggest that induction of tolerance to cat allergen is an allergen-specific phenomenon that cannot be attributed to endotoxin or family choice. The strength of the IgE antibody response to dust mite in humid climates could contribute to the increased prevalence and severity of asthma.     

Relationship among house-dust mites, Der 1, Fel d 1, and Can f 1 on clothing and automobile seats with respect to densities in houses.

BACKGROUND: Locations where there are no dust mites or pets present may contain allergens that pose a risk factor for sensitizing and inducing rhinitis and asthma. OBJECTIVE: The purpose of this study was to investigate the relationship among the prevalence of mites and mite, dog, and cat allergens in homes, on clothing, and on automobile seats. METHODS: Over a 2-year period (July 1998 to July 2000), dust mite and mite, dog, and cat allergen densities were determined in homes, associated automobiles, and on the clothing of the drivers. During this period 87 homes were sampled one to five times each. RESULTS: Low levels of live and dead mites were present in most dust samples obtained from automobile seats and in 16% from clothing. Seventy-two and 50% of the home samples had >2 microg and >10 microg Der l/g of dust, respectively, whereas 23% of automobiles seat samples had >2 microg Der l/g of dust with a mean of 1.3 microg/g. Mite and Der 1 densities were not different for homes with or without pets. However, homes with pets had significantly more Fel d 1 or Can f 1 allergen than homes without pets. Homes without cats and dogs had an average of 93 and 29 microg/g of Fel d 1 and Can f 1, respectively, which was well above threshold levels for sensitization and induction of allergic reactions. Although most clothing had detectable levels of pet allergen, the levels of these allergens were low. CONCLUSIONS: Der 1 densities in some automobiles were sufficiently high (>2 microg/g of dust) to be risk factors for sensitization and allergic reactions. However, most automobile seats had levels of dog and cat allergen that were well above the threshold levels considered to be risk factors for both sensitization and symptoms, regardless of the presence of a pet in the home. The presence of live and dead mites and mite, cat, and dog allergens in automobiles and on clothing suggests that both are vehicles in the dispersal of mites and mite and pet allergen.     

The relevance of maternal immune responses to inhalant allergens to maternal symptoms,passive transfer to the infant,and development of antibodies in the first 2 years of life

BACKGROUND: Asthma and other atopic diseases are strongly hereditary. Although the mother might play a special role, the mechanisms for such an effect are not clear. OBJECTIVE: We sought to investigate the influence of maternal immune responses to cat and mite allergens on (1) maternal symptoms, (2) the development of immune responses in the infant, and (3) the development of allergic disease during the first 3 years of life. METHODS: In sera from 465 mothers and 424 infants (cord blood), as well as in sera from 230 of the children at age 2 to 3 years, total IgE and IgE antibodies were measured by using CAP testing; IgG and IgG4 antibodies for the cat allergen Fel d 1 were measured by means of radioimmunoprecipitation. RESULTS: In both mothers and children, approximately 15% of sera contained IgG antibodies to Fel d 1 without IgE antibodies to cat. The strongest predictor of the maternal IgG antibody response was exposure to greater than 8 microg of Fel d 1/g of dust. Thus approximately 70% of children living in a house with a cat had received IgG antibodies from their mothers. In many cases the infant received IgG and IgG4 antibodies to Fel d 1 from a nonallergic mother. Maternal IgE antibodies were consistently associated with asthma; by contrast, the IgG antibody was not independently related to asthma but was related to rhinitis in the mothers (odds ratio, 2.6; 95% CI, 1.1-6.2) and to eczema in children. At age 3 years, 13 of 230 sera contained IgE antibodies to mite, but only 5 had IgE antibodies to cat. CONCLUSIONS: A significant proportion (approximately 15%) of mothers and children exposed to high concentrations of cat (but not mite) allergens have serum IgG antibodies without IgE antibodies. This IgG antibody is freely transferred to the infant and might influence IgG antibody production in the child. The results indicate the importance of understanding the mechanisms of tolerance to cats and raise questions about the independent role of the mother in the inheritance of allergy.     

Fel d 4, a cat lipocalin allergen

BACKGROUND: Cat allergy is unique among allergy to mammals in that the major allergen Fel d 1 is a uteroglobin-like protein and not a lipocalin. The biochemical spectrum of the cat allergens is thus uncertain, particularly with regard to the role that a cat lipocalin protein may play in sensitization to cats in allergic individuals. OBJECTIVE: To analyse cDNA encoding a lipocalin allergen and the corresponding recombinant allergen at both the molecular and immunological levels. METHODS: A submandibular salivary gland cDNA expression library was constructed and screened for clones producing IgE-binding polypeptides. cDNA encoding a lipocalin allergen and its corresponding recombinant allergen were analysed. RESULTS: An IgE binding molecule with high sequence identity to the boar salivary lipocalin and the horse lipocalin Equ c 1 allergen was isolated and designated, Fel d 4. Serum from 62.96% of cat-allergic subjects examined had measurable IgE antibody to Fel d 4 but typically at low levels. Despite this in 47% of sera the anti-Fel d 4 IgE titres were higher than the anti-Fel d 1 titres. IgE binding to the lipocalin allergen could be blocked by an allergen extract from cow and to a lesser degree by extracts from horse and dog. CONCLUSION: Fel d 4 is a lipocalin allergen produced by the cat, which binds IgE at relatively high frequency in cat-sensitive individuals. The allergen provides not only a means for investigating differences in the immune response to lipocalin allergens from that found for other mammalian species but also an important reagent for the diagnosis of cat allergy.     

Purified natural and recombinant Fel d 1 and cat albumin in in vitro diagnostics for cat allergy

BACKGROUND: Current diagnostics and therapeutics for cat allergy are based on cat epithelial extracts originating from highly variable source materials. This gives rise to several problems: variability of allergen composition, contamination with house dust mite allergens, and potential transfer of pathogenic agents. OBJECTIVE: The aim of this study was to investigate the feasibility of replacing cat epithelial extracts with purified natural or recombinant allergens. METHODS: Sera (n = 509) were selected on the basis of a positive cat RAST result and tested in a RAST for IgE reactivity to purified Fel d 1, cat albumin (CA), or both. The analysis was performed with both natural and recombinant allergens. In addition, some sera were further analyzed by means of immunoblotting. A serum pool was used for cat RAST inhibition with purified natural and recombinant allergens as inhibitors. RESULTS: Natural and recombinant Fel d 1 caused very similar results: 94.1% and 96.1% positive test results, respectively. In general, the negative sera were low responders to cat extract. The addition of CA (16.7% positive sera) resulted in a decrease in the number of discrepencies between purified allergens and whole extract to 2.8%. Only for 2% of all sera, sensitization to cat was largely explained by IgE reactivity to CA. IgE reactivity to Fel d 1 accounts for 88% of the total IgE response to cat allergens, as was demonstrated by RAST, with Fel d 1 concentrations nearing saturation. Recombinant Fel d 1 performed equally well in the RAST analysis. Recombinant CA was succesfully expressed in the yeast Pichia pastoris, and its immune reactivity closely resembled that of its natural counterpart. CONCLUSION: Natural and recombinant Fel d 1 and CA are good candidates for replacing ill-defined cat dander extracts in diagnostics for cat allergy. Although CA is not essential for the vast majority of cat-sensitized patients, some subjects are selectively sensitized to this serum protein.     

Exposure to an abundance of cat (Fel d 1) and dog (Can f 1) allergens in Swedish farming households

BACKGROUND: Earlier studies have shown that farmers are to a low degree sensitized to animal allergens. We have measured the amount of cat (Fel d 1) and dog (Can f 1) in farm households and examined the relationship between exposure and sensitization to cat and dog allergens. METHODS: Dust samples from the homes of 403 farmers who had participated in an epidemiologic follow-up study on respiratory symptoms were analyzed for allergen content by two-site ELISA methods. RESULTS: Fel d 1 was detected in 99.5% of the farmers' households ranging from 0.055 to 1455 microg/g dust in mattresses (GM 13.2) and to 3775 microg/g dust in living-room carpets (GM 17.1). Can f 1 was detected in 90.6% of the households from 0.2 to 116 microg/g dust in mattresses (GM 2.0) and to 504 microg/g dust in carpets (GM 4.3). Homes with pets present had the highest levels of the allergens (P<0.001). A total of 8.4% and 7.4% of the farmers were sensitized to cat and dog, respectively. A significant correlation was noted between exposure to the allergens and specific IgE to cat and dog, respectively (P<0.001). Sensitization to cat (OR = 4.9) and dog (OR = 17.8) was significantly associated with asthma. CONCLUSIONS: In spite of the abundance of Fel d 1 and Can f 1, farmers are only to a low degree sensitized to cats and dogs.     

Exposure and sensitization in infants and children

The complex relationship between allergen exposure, atopic sensitization and asthma in individuals and in populations has recently been a subject of controversy. A number of studies have demonstrated that allergen exposure in sensitized asthmatic individuals increases the severity of disease. A simple dose-response relationship between mite allergen exposure and specific sensitization in infants and children has been confirmed. However, the concept that there is a direct relationship between allergen exposure and the initiation of asthma has been challenged. The relationship between allergen exposure and subsequent disease development is complex, and is confounded by a number of important factors. Populations and individuals are exposed to a mixture of several allergens, irritants and pollutants, and we know very little about the impact of these mixtures and their possible synergistic effect. The dose-response relationship between allergen exposure and allergic disease may not be linear, and may be different for different allergens. For example, a protective effect of cat ownership on sensitization and allergic disease has been reported, raising the question of whether the dose-response relationship between exposure and sensitization may be different for cat compared with mite allergen. It has been suggested that many children who are exposed to a high level of cat allergen make a modified T helper type 2 response, characterized by the presence of IgG4 antibody to cat proteins without becoming allergic (i.e. no IgE response), which could be regarded as a form of tolerance. This could explain a decreased risk of asthma in children living in homes with cats, without invoking a concept of a shift in the balance of T helper types 1 and 2 responses. Cat allergen is ubiquitous, and passive exposure (e.g. home without cats and public places) may induce specific IgE responses in non-cat owners, whereas those exposed to very high levels of cat allergen may initially mount an IgE response, which may be replaced by a modified T helper type 2 response (tolerance). It is likely that the population susceptibility to allergic sensitization and also end-organ responsiveness has altered, and allergen exposure may still be important in initiating disease in an increasingly susceptible population, although the pattern may differ for different allergens.     

Health impacts of second-hand exposure to cat allergen Fel d 1 in infants

BACKGROUND: Recent cross-sectional studies suggested that highest sensitization prevalences occur with moderate cat allergen exposures. We aimed to assess the impact of moderate levels of second-hand cat allergen exposure on the incidence of specific sensitization and wheezing in the framework of a birth cohort study. Therefore we restricted our analysis to infants without a cat at home since birth. METHODS: At infant's age 3 months, cat allergen levels were measured in the mattress dust of 1840 families without cats. At age 2 years, serum IgE specific to Fel d 1 was analyzed. Incidence of wheezing apart from respiratory infection was assessed by questionnaire. Logistic regression models were used to calculate adjusted odds ratios (OR) for the association between second-hand cat allergen exposure and health outcomes. RESULTS: Until age 2 years, 13 of 1301 infants (1%) were sensitized to cat allergen and 56 of 1492 infants (4%) had ever-wheezing without infection. Early exposure to second-hand cat allergen levels >or= 1 microg/g dust increased substantially the risk for specific sensitization to Fel d 1 (OR 10.9, 95% CI 3.4-35.0) and ever-wheeze without infection (OR 2.0, 95% CI 1.1-3.9) at age 2 years. CONCLUSIONS: Second-hand exposure to cat allergen in homes without cats is detrimental in terms of allergy development in infants.     

Longitudinal study on the relationship between cat allergen and endotoxin exposure, sensitization, cat-specific IgG and development of asthma in childhood--report of the German Multicentre Allergy Study (MAS 90)

BACKGROUND: Controversial data have emerged regarding the question whether cat exposure in childhood favours or decreases the risk of sensitization and allergic airway disease. In a prospective birth-cohort study, we assessed the association between longitudinal cat allergen exposure, sensitization (immunoglobulin E, IgE), IgG antibody (ab) levels to cat and the development of asthma in children up to the age of 10 years. METHODS: Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 10 years were available for 750 children. Assessments included yearly measurements of specific serum IgE to cat and at age 6 and 18 months, 3, 4 and 10 years measurement of cat allergen Fel d 1 in house dust samples. Additionally, Fel d 1-specific IgG ab were determined in 378 serum samples of 207 children. Endotoxin exposure in mattress dust was measured in a subgroup of 153 children at age 10 years. From age 4 years on, International Study of Asthma and Allergy in Childhood (ISAAC) questionnaires were completed yearly in order to assess the prevalence of wheeze and asthma. RESULTS: Serum IgG-levels to cat showed a large variation, however, intraindividually values showed rather constant concentration over a longer time period. The IgG levels at school-age correlated with cat allergen exposure during the first 2 years of life. Specific IgE to cat was clearly associated with wheeze ever, current wheeze and bronchial hyperresponsiveness (BHR), this was also observed for children with specific IgE ab to cat (>0.35 kU/l) plus IgG levels above 125 U/ml. A large percentage of very highly exposed children showed high IgG but no IgE responses to cat, however, not all highly exposed children were found to be protected from sensitization. Children with IgG but without IgE ab to cat showed the lowest prevalence of wheeze ever and current wheeze despite high cat allergen exposure, however, this trend did not achieve significance. While homes of cat owners showed higher Fel d 1 concentrations than homes without cats, homes of cat owners were not found to have higher endotoxin levels in carpet dust samples than homes without cats. CONCLUSIONS: We could confirm that high cat allergen exposure in a cohort with lower community prevalence of cats is associated with higher serum IgG and IgE levels to cat in schoolchildren. Sensitization to cat allergen (IgE) is a risk factor for childhood asthma. While exposure to cat allergen during infancy is associated with sensitization (IgE), only in the very highly exposed children the likelihood of sensitization (IgE) is decreased and high IgG levels to cat without IgE were associated with low risk of wheeze. However, cat-specific IgG ab levels did not protect children with IgE-mediated sensitization from wheeze.     

Mite (Der p 1, Der f 1) and cat (Fel d 1) allergens in the homes of babies with a family history of allergy

Carpet and floor dust samples were collected in four different seasons, from 39 Swedish homes of babies with a family history of allergy. House-dust mite ( Der p 1, Der f 1 ) and cat ( Fel d 1 ) allergen contents were determined by mab ELISA, and the levels were related to various environmental factors. Both mite and cat antigens were detected in 94% of the samples and in all homes, but the levels were low ( Der p 1 , range 15 ng–1944 ng/g fine dust; Der f 1 , range 14 ng–264 ng/g of fine dust; Fel d 1 , range 16 ng–3120 ng/g fine dust). Mite-allergen levels were significantly higher ( P <0.001) in floor dust than in carpets, and D. pteronyssinus predominated. In contrast, the levels of cat antigen were significantly ( P <0.05) higher in carpets than in floor dust. There was no clear relation between mite-allergen levels and type of house, except that the higher values were found in homes with dampness problems. Cat-allergen levels were higher than total mite-allergen content, and the highest levels were found in homes with a cat ( P <0.05). Rather high concentrations of cat allergen were also found in homes without a cat, which may explain why cat sensitization is so common in Sweden. As the prevalence of house-dust mite sensitivity is increasing in Swedish children, and as the individual patient threshold for eliciting symptoms varies, we suggest that sensitization may possibly occur at a lower exposure level than generally accepted as risk level for sensitization (2 μg/g dust).     

Fel d 1 and Can f 1 in settled dust and airborne Fel d 1 in allergen avoidance day-care centres for atopic children in relation to number of pet-owners, ventilation and general cleaning

BACKGROUND: Special day-care centres for atopic children have been established in Sweden. OBJECTIVE: To study concentrations of cat (Fel d 1) and dog (Can f 1) allergens in settled dust and airborne cat allergen in day-care centres in relation to pet ownership among children and staff, ventilation and general cleaning. METHODS: Twelve allergen avoidance day-care centres and 22 conventional day-care centres were included in the study. Settled dust was collected and analysed with ELISA. Airborne cat allergen levels were measured in eight allergen avoidance and seven conventional centres with a personal air sampler and analysed with an amplified ELISA. Air change rate per hour (ACH) was measured. A questionnaire which focused on keeping of cat and dog among staff and children and frequency of general cleaning was used. RESULTS: In the allergen avoidance day-care centres neither children nor staff reported ownership of cats or dogs, compared with 21/22 of the conventional centres in which children and staff kept furred animals. Fel d 1 and Can f 1 were found in settled dust in all day-care centres. In the allergen avoidance compared with the conventional centres the concentrations of Fel d 1 and Can f 1 were lower, Fel d 1: median 0. 64 microg/g vs 5.45 microg/g and Can f 1: 0.39 microg/g vs 2.51, both P < 0.001, and airborne Fel d 1 was also lower in the allergen avoidance centres compared with the control centres, 1.51 ng/m3 vs 15.8 ng/m3, P = 0.002. A correlation was found between airborne and settled Fel d 1, rs = 0.75, P < 0.001. Furthermore, a correlation was found between increased ACH and decreased levels of Fel d 1 in the air in the day-care centres with no cat-owners, rs = - 0.86, P = 0.007. No relation was found between levels of cat or dog allergen and amount of general cleaning. CONCLUSION: Not keeping pets seems to reduce children's exposure to pet-allergen in their 'working environment'. Additionally, appropriate ventilation seems to reduce Fel d 1 in the air in day-care centres.     

Mite (Der p I, Der f I), cat (Fel d I) and dog (Can f I) allergens in dust from Swedish day-care centres

Early exposure to allergens is important for sensitization to inhalant allergens and it has been reported that there is a causal relationship between allergen exposure and bronchial asthma. We investigated the levels of major mite (Der p I/Der f I), cat (Fel d I) and dog (Can f I) allergen levels in dust collected from various locations in seven day-care centres (22 sections). The allergen levels were related to the characteristics of the day-care centres. Children and staff were questioned about contacts with animals, and cleaning personnel were asked about methods and frequency of cleaning. Mite allergen was found in nine of the 22 sections. The concentrations varied between < 16 ng/g and 106 ng/g dust (median < 16 ng/g). Mite allergen was not detected in any floor dust sample. Cat and dog allergen was detected in all centres and sections. The concentrations of dog allergen (median 4.3 μg/g; range < 60 ng-21 μg/g) were significantly higher (P < 0.05) than that of cat allergen (median 1.6 μg/g; range < 16 ng-22.8 μg/g). Higher amounts of both Fel d I and Can f I were observed on mattresses/sofas/cushion like toys and curtains than on tables/chairs and floors. The levels of cat or dog allergen on floors significantly correlated with the total number of children and staff with either a cat or a dog at home and or frequent contacts with them. Neither cleaning methods nor the frequency of cleaning influenced the allergen concentrations. The concentration of Fel d I was significantly lower (P < 0.05) in washed than in never washed curtains. We conclude that Fel d I and Can f I allergens are ubiquitous in day-care centres. The allergens are probably carried there in the clothes of children and staff. Day-care centres should be considered a cause of exposure to indoor allergens. Curtains, toys and upholstery were the most important reservoirs. We suggest that the concentration of allergen in curtains reflects long-term exposure to airborne indoor allergens, since they are mainly exposed to airborne allergens.     

Quantitative measurement of IgE antibodies to purified allergens using streptavidin linked to a high-capacity solid phase

BACKGROUND: Commercially available assays for IgE antibody provide results in international units per milliliter for many allergen extracts, but this is not easily achieved with purified or novel allergens. OBJECTIVE: To develop assays for IgE antibody suitable for purified or novel allergens by using a commercially available immunosorbent. METHODS: Streptavidin coupled to a high-capacity immunosorbent (CAP) was used to bind biotinylated purified allergens from mite (Der p 1 and Der p 2), cat (Fel d 1), and dog (Can f 1). Assays for IgE antibody to these allergens were performed on sera from children (asthma and control) as well as adults with atopic dermatitis. RESULTS: The results were validated by serial dilution of sera with high and low levels of IgE antibody and were quantitated in international units per milliliter by using a standard curve. Values for IgE antibody to Der p 1, Der p 2, and Fel d 1 correlated with values obtained with the allergen extracts (r2 = 0.80, 0.84, and 0.95, respectively; P < .001 in each case). Furthermore, the values for IgE antibody in sera from children with high exposure to mite and cat allergens demonstrated 10-fold higher levels of IgE antibody to Der p 1 and Der p 2 than to Fel d 1 (P < .001). CONCLUSION: The streptavidin immunosorbent technique provides a new method for quantifying IgE antibody to purified proteins. The results provide evidence about the high quantities of IgE antibody to purified inhalant allergens in patients with atopic dermatitis. In addition, the results demonstrate major differences in IgE antibodies specific for mite and cat allergens among children with high exposure to both allergens.     

Dog allergen (Can f 1) and cat allergen (Fel d 1) in US homes: results from the National Survey of Lead and Allergens in Housing

BACKGROUND: Exposures to dog and cat allergens are believed to play important roles in the etiology of asthma; however, the levels of these allergens have never been assessed in a representative sample of US homes. OBJECTIVE: The objective of this study was to estimate and characterize exposures to Can f 1 (dog allergen) and Fel d 1 (cat allergen) in US homes. METHODS: Data were obtained from the National Survey of Lead and Allergens in Housing, a nationally representative survey of 831 US homes. Vacuumed-collected dust samples from the bed, bedroom floor, living room floor, and living room sofa were analyzed for concentrations of Can f 1 and Fel d 1 (micrograms of allergen per gram of dust). RESULTS: Although a dog or cat had lived in only 49.1% of homes in the previous 6 months, Can f 1 and Fel d 1 were detected in 100% and 99.9% of homes, respectively. Averaged over the sampled sites, geometric mean concentrations (microg/g) were 4.69 for Can f 1 and 4.73 for Fel d 1. Among homes with an indoor dog and cat, respectively, geometric mean concentrations were 69 for Can f 1 and 200 for Fel d 1. Among homes without the indoor pet, geometric mean concentrations were above 1.0. The independent predictors of elevated concentrations in homes without pets were all demographic variables that were also linked to a higher prevalence of pet ownership. CONCLUSIONS: Can f 1 and Fel d 1 are universally present in US homes. Levels that have been associated with an increased risk of allergic sensitization were found even in homes without pets. Because of the transportability of these allergens on clothing, elevated levels in homes without pets, particularly among demographic groups in which pet ownership is more prevalent, implicate the community as an important source of these pet allergens.     

Efficacy of dry-cleaning in removing Fel d 1 allergen from wool fabric exposed to cats.

BACKGROUND: The main cat allergen (Fel d 1) is ubiquitous, having been found even in indoor environments and public places where a cat has never been kept. Clothes of cat owners constitute a carrier for the distribution of Fel d 1 allergen in these environments. Schools, for example, may be a site of indirect exposure to cat allergens. OBJECTIVE: Our goal was to investigate the efficacy of commercial dry-cleaning in removing cat allergens from wool fabrics that had been exposed to cats to evaluate a possible preventive procedure. METHODS: Twenty-six identical wool "squares" (80 x 100 cm) were put in cat baskets for 1 week. In our laboratory, the squares were cut in half (40 x 50 cm), and one half was subjected to high-volume sampling for 5 minutes in a cat-free room. The other half was subjected to commercial dry-cleaning and then the high-volume sampling. Five wool squares not exposed to cats served as controls. Dust was collected from the wool squares with a high-volume air sampler. Particulate material was harvested onto glass fiber filters (AP 20 Millipore, Milan, Italy) with 25-mm diameter and 2-microm pore size. Each dust sample was assayed by affinity-purified monoclonal antibody against purified Fel d 1. The results were expressed as micrograms per filter. Statistical analysis was done by using the paired t test. RESULTS: Before dry-cleaning, Fel d 1 allergen was detected on all cat-exposed wool squares. No appreciable cat allergen was detected on control materials. After commercial dry-cleaning, the amounts of Fel d 1 extracted from cat-exposed squares were significantly reduced (t = 14.63; P < 0.001) but not abolished. Three of the five control squares were contaminated by Fel d 1. CONCLUSIONS: Commercial dry-cleaning effectively removes large amounts of cat allergen from wool materials exposed to cats but does not completely abolish this protein. Further, low Fel d 1 contamination may occur during this procedure.     

Changes in cat specific IgE and IgG antibodies with decreased cat exposure

BackgroundCurrent understanding of the effects of reducing exposure to cat allergens is limited. It has also become clear that there are different forms of immune response to cat allergens.ObjectiveTo investigate changes in skin tests and cat specific IgG and IgE antibodies when students from a home with a cat move to a college dormitory.MethodsNinety-seven college students participated in a prospective study that consisted of allergy skin prick testing and serum measurement of IgE and IgG antibodies to cat at the beginning and end of one academic year in college. A subgroup returned for follow-up at the end of 2 years.ResultsAmong 97 students, 33% had IgG antibodies to Fel d 1 but no evidence of sensitization, 25% had positive skin test results and/or serum IgE antibodies, and 42% had negative skin test results and no detectable serum antibodies. Among the non–cat sensitized students with IgG antibodies, the titers decreased during 8 months (P = .002). Titers of IgG4 to Fel d 1 also decreased (P < .001). Among the sensitized students, no change in IgE antibodies to cat occurred in 8 months (P = .20), whereas Fel d 1 specific IgG antibodies decreased (P < .001). Thus, ratios of IgG to IgE decreased highly significantly (P = .007). Among the students with negative skin test results who returned for follow-up (n = 56), none developed positive skin test results or serum IgE antibodies.ConclusionUnder conditions of marked decrease in exposure, no participants developed new-onset sensitization. Among the individuals sensitized at study entry, there were major decreases in the ratio of IgG to IgE.     

Human T and B cell immune responses to Fel d 1 in cat-allergic and non-cat-allergic subjects

Background In allergic individuals exposure to allergen leads to the induction of allergen-specific IgE which, upon binding to its high affinity receptors on mast cells and basophils. primes these cells for degranulation. This degranulation. a result of specific IgE allergen-interaction, initiates the debilitating symptoms of allergy and the potentially life-threatening symptoms of anaphylaxis. The lack of symptoms following antigen encounter by non-allergic individuals is probably due to the undetectable levels of allergen-specific IgE in the plasma of non-allergic individuals. Objective To compare the immune responses of allergic and non-allergic individuals. Method We compared the immune responses of 42 cat-allergic subjects with 16 nem-cat-allergic subjects to the major cat allergen. Fel d I. We have measured plasma immunoglobulin levels and the proliferative responses of fel d 1 primed T cell lines to Fel d 1 peptides. Results While these two groups have similar levels of Fel d 1 specific IgG. only subjects in the cat-allergic group have detectable Fel d 1 specific IgE. Affinity purified Fel d 1 was used to generate T cell lines from peripheral blood mononuclear cells of these same subjects. The proliferative responses of these T cell lines to intact Fel d 1 and a set of overlapping peptides covering the entire sequence of the molecule demonstrated that the pattern of epitope recognition was similar in both groups. Conclusion Our data suggest that factors other than T cell recognition of specific epitopes are responsible for the nature of allergic immune responses generated when allergen is encountered.     

Cat (Fel d I), dog (Can f I), and cockroach allergens in homes of asthmatic children from three climatic zones in Sweden

We have investigated the levels of cat ( Fel d I), dog ( Can f I), and cockroach ( Per a I) allergens in dust from bedrooms, living rooms, kitchens, and bathrooms from 123 homes of asthmatic children in three zones of Sweden with varying climates. Absolute indoor humidity (AIH), relative humidity (RH), rate of ventilation in air changes per hour (ach), and number of airborne particles were also measured. Fel d I, Can f I, and Per a I allergen contents were determined by mab ELISA, and the levels were related to various environmental factors. The major cat allergen. Fel d I, was detected in all homes, and the concentrations varied between 16 ng and 28000 ng/g fine dust. The dog allergen, Can f I, was detected in 85% of the homes, and the levels varied from 60 ng to 866000 ng/g dust. Cockroach allergen was detected in only one home (40 ng/g). Fel d I and Can f I allergens were equally distributed geographically. Dust from living rooms contained significantly higher ( P < 0.05) concentrations of both Fel d I and Can f I allergens than dust from bedrooms, kitchens, and bathrooms. The levels tended to be higher in homes with poor ventilation (<0.5 ach) and in homes with wall-to-wall carpets. Significantly higher ( P < 0.01) numbers of airborne particles were found in homes with high humidity (i.e., AIH ≥ 7 g/kg or RH ≥ 45%). We conclude that pet allergens are ubiquitous in different climatic regions, being found in bedrooms, living rooms, kitchens, and bathrooms. Current or previous presence of a cat or dog, high indoor humidity, presence of wall-to-wall carpets, and poor ventilation all increase the risk for high allergen exposure. In contrast, cockroach allergens arc rarely found in a temperate climate.     

High-level expression of immunoreactive recombinant cat allergen (Fel d 1): Targeting to antigen-presenting cells

BACKGROUND: Cat allergen Fel d 1 is a heterodimer encoded by 2 separate genes that has been difficult to produce as a fully immunoreactive molecule. OBJECTIVE: We sought to engineer recombinant (r) Fel d 1 with IgE and IgG antibody binding comparable with that of the natural allergen that could be targeted to antigen-presenting cells. METHODS: The rFel d 1 chains were coexpressed in baculovirus, either linked to the anti-CD64 antibody H22 (rFel d 1 H22(+)) or alone (rFel d 1 H22 (-)). Binding of expressed allergens to mouse and human antibodies was compared with that of natural (n) Fel d 1 by means of enzyme immunoassay and antigen-binding and inhibition RIAs. Binding of rFel d 1 H22 (+) to the CD64 receptor on leukocyte subpopulations and on the THP -1 cell line was analyzed by means of flow cytometry. RESULTS: The baculovirus-expressed allergens migrated with molecular weights of 49 kd (rFel d 1 H22(+)) and 22 kd (rFel d 1 H22 (-)). The rFel d 1 inhibited IgG antibody binding to nFel d 1 by greater than 95% and showed identical dose-dependent inhibition curves. There was an excellent quantitative correlation between IgE and IgG antibody binding to rFel d 1 and nFel d 1 in sera from patients with cat allergy (IgE: n = 258, r = > 0.72,P <.001). The rFel d 1 H22(+) bound to monocytes but not to lymphocytes or neutrophils, and binding of rFel d 1 H22(+) to THP-1 cells was inhibited by a soluble CD64 fusion protein. CONCLUSIONS: Recombinant Fel d 1 chains have been successfully coexpressed as mature proteins with comparable immunoreactivities to nFel d 1. The rFel d 1 can be targeted to antigen-presenting cells through CD64. These constructs will facilitate structural studies of Fel d 1 and the development of improved allergy diagnostics and therapeutics.