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1.  The indoor air and asthma: the role of cat allergens 
Purpose of review
The objective is to discuss recent progress in our understanding of the role of the indoor environment in asthma, focusing on the special role of cat allergens.
Recent findings
Sensitization to Fel d 1 is the dominant event in inhalant responses to cat; however, there are also IgE responses to the lipocalin (Fel d 4), to cat albumin (Fel d 2), and to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) on cat IgA (Fel d 5w) and other molecules. The dose response and routes of sensitization for these allergens are now thought to be diverse. It is important to remember that exposure outside a house with a cat is sufficient to cause sensitization. Furthermore, the only solid evidence about a role in asthma relates to Fel d 1. Recently, it has been shown that tolerance associated with early exposure to cats can persist to age 18 and that IgE to alpha-gal (on cat IgA) is not related to asthma. In addition, a recent study of anti-IgE reinforces the evidence that IgE antibodies to indoor allergens make a major contribution to asthma severity.
Exposure to Fel d 1 in a home with a cat is far higher than the levels necessary to induce an allergic (IgE antibody) response. In keeping with that, children may develop tolerance, which can be long-lived. In addition, there is increasing evidence that IgE antibodies to an inhalant allergen, such as Fel d 1, dust mite, or cockroach, are causally related to lung inflammation and asthma.
PMCID: PMC3707607  PMID: 22081090
asthma; cats; inhalant allergens; Fel d 1; long-term tolerance
2.  Galactose-α-1,3-Galactose–Specific IgE Is Associated with Anaphylaxis but Not Asthma 
Rationale: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract.
Objectives: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens.
Methods: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131).
Measurements and Main Results: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001).
Conclusions: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.
PMCID: PMC3326422  PMID: 22281828
α-gal; red meat allergy; ticks; total serum IgE; ectoparasite
3.  Flow Cytometry Imaging Identifies Rare Th2 Cells Expressing TSLP Receptor in a “Pro-Allergic” Milieu 
TSLP is expressed at sites of allergic inflammation, including eczematous skin. This cytokine has been reported to exert its Th2-inducing properties through dendritic cells. Expression of TSLP receptor on the surface of activated Th2 cells could amplify Th2 responses at inflamed sites through the direct actions of TSLP.
To rigorously test whether Th2 cells induced by “pro-allergic” factors express TSLP receptor and characterize these cells using an experimental platform that combines flow cytometry with microscopic capabilities.
CD4+ T cells isolated from patients with atopic dermatitis or normal healthy controls were co-cultured with autologous dendritic cells in the presence of Th2-promoting stimuli (TSLP±allergen and staphylococcal enterotoxin B±TSLP). Surface expression of TSLP receptor was analyzed by image-based flow cytometry and responsiveness of purified T cells to TSLP was assessed by phosphorylation of STAT5 and cytokine secretion.
Th2-promoting stimuli induced a robust population of activated Th2 cells (CD25+IL-4+). Regardless of the nature of the stimulus, flow cytometry imaging confirmed that T cells expressing TSLP receptor were rare, constituting a minor fraction of the IL-4+ T cell pool; however, TSLP-responsiveness was nonetheless detectable. Analysis of cell size and nuclear morphology revealed preferential expression of TSLP receptor on IL-4-expressing cells undergoing mitosis. Analysis of lesional skin in atopic dermatitis supported the view that rare IL-4+ T cells expressing TSLP receptor are present at inflamed sites.
In a “pro-allergic” milieu, TSLP receptor is preferentially expressed on rare actively dividing Th2 cells. The direct action of TSLP on T cells could amplify Th2 responses at sites of allergic inflammation.
PMCID: PMC3034251  PMID: 20888036
TSLP; TSLP receptor; atopic dermatitis; Th2 cells; flow cytometry imaging

Results 1-3 (3)