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PubMed2000

Genetic variants of IL-13 signalling and human asthma and atopy.

Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Ralpha and either gammac or IL-13Ralpha1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ralpha and IL-13Ralpha1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy. Recent animal model data suggest that IL-13 is a central cytokine in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity. We investigated the role of common genetic variants of IL-13 and IL-13Ralpha1 in human asthma, considering IgE levels. A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 2.31, 95% CI 1.33-4.00]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population. Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects. Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction. A non-coding variant of IL-13Ralpha1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3. 38 in males, 1.10 in females) rather than asthma. Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed.

Adult↗
PubMed2005

Birth order, atopy, and risk of non-Hodgkin lymphoma.

BACKGROUND: Immune deficiency is a strong risk factor for non-Hodgkin lymphoma (NHL), but whether or not other forms of immune dysregulation are associated with NHL risk is unknown. We investigated associations between atopy, which is associated with a Th2-dominant immune response, and NHL risk. Because late birth order and childhood crowding are inversely associated with atopy, we also investigated their associations with NHL risk. METHODS: We carried out a population-based case-control study among adults aged 20-74 years in New South Wales and the Australian Capital Territory, Australia. NHL patients without clinically apparent immune deficiency (N = 704) were selected from a cancer registry, and control subjects (N = 694) were randomly selected from state electoral rolls and frequency-matched to case patients by age, sex, and area of residence. Birth order, childhood crowding, and history of atopic conditions (hay fever, asthma, eczema, and specific allergies) were assessed by questionnaire and interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models that included the matching variables as covariates. RESULTS: The odds ratios for developing NHL were 0.52 (95% CI = 0.32 to 0.84) for only children, 0.55 (95% CI = 0.40 to 0.75) for first-born children, 0.70 (95% CI = 0.51 to 0.96) for second-born children, and 0.81 (0.57 to 1.14) for third-born children (all compared with fourth- or later-born children) (P(trend)<.001). Indicators of crowding in later childhood, such as sharing a bed or bedroom, were not associated with NHL risk. A history of atopic conditions was associated with a reduced risk of NHL; this reduction was statistically significant for hay fever (OR = 0.65, 95% CI = 0.52 to 0.82) and food allergies (OR = 0.29, 95% CI = 0.20 to 0.42). CONCLUSIONS: Early birth order and its immunologic consequence, a Th2-dominated immune response, as reflected by a history of atopic disease, are associated with a reduced risk of NHL.

Adult↗
PubMed2007

Atopy and risk of non-Hodgkin lymphoma.

BACKGROUND: A possible connection between allergy and cancer has been suspected, but allergy-related conditions or atopy have been inconsistently associated with reduced risks of non-Hodgkin lymphoma. We investigated this association in a population-based case-control study and in a prospective study with prediagnostic blood specimens. METHODS: We carried out a population-based study of 3055 case patients with non-Hodgkin lymphoma and 3187 control subjects in Denmark and Sweden, including questionnaire information on allergy and blood specimens, and a nested case-control study within a prospective cohort of more than 400,000 Finnish women. In the second study, serum specimens from the 198 case patients who developed non-Hodgkin lymphoma within a median of 8.9 years after the blood was drawn were matched with serum specimens from 594 control subjects. In both studies, laboratory-based evidence of allergy (atopy) was determined in serum on the basis of specific IgE reactivity to common inhalant allergens. Dissemination of disease was classified by the Ann Arbor system. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. RESULTS: In the first study, ever having hay fever, but not other allergic conditions, was associated with a reduced risk of non-Hodgkin lymphoma. In particular, subjects with specific IgE reactivity in serum had a 32% (95% CI = 20% to 42%) lower risk of overall non-Hodgkin lymphoma than those without such reactivity. However, among case patients, dissemination of the disease was strongly inversely associated with specific IgE reactivity. In the second (i.e., prospective) study, no association was found between non-Hodgkin lymphoma and specific IgE reactivity, except possibly immediately before a diagnosis of non-Hodgkin lymphoma (> or = 10 years before diagnosis, OR = 1.00, 95% CI = 0.48 to 2.09; 5-9 years before, OR = 0.95, 95% CI = 0.50 to 1.84; 1-4 years before, OR = 0.33, 95% CI = 0.11 to 1.02; and < 1 year before, OR = 0.27, 95% CI = 0.03 to 2.31). CONCLUSION: Allergy may not be causally associated with the risk of non-Hodgkin lymphoma. The inverse association observed in some case-control studies may arise because non-Hodgkin lymphoma suppresses the immunologic response to allergens.

Adult↗
PubMed2000

Traffic-related air pollution is associated with atopy in children living in urban areas.

Traffic emissions are a major source of air pollution in Western industrialized countries. To investigate the association between traffic-related air pollution and parameters of atopy, we studied 317 children 9 years of age living near major roads in two urban areas and one suburban area of a city in West Germany. Atopic sensitization was analyzed by skin-prick testing and determination of allergen-specific serum immunoglobulin E. Parents recorded allergic symptoms in a symptom diary, and physicians assessed allergic diseases. Personal NO2 exposure and NO2 concentrations in front of each child's home were measured. Outdoor NO2 was a good predictor for traffic exposure but a poor predictor for NO2 exposure at the personal level. Atopy was found to be related to outdoor NO2 (odds ratio for the association between symptoms of allergic rhinitis and outdoor NO2 = 1.81; 95% confidence interval = 1.02-3.21) but not to personal NO2 (odds ratio for the association between symptoms of allergic rhinitis and personal NO2 = 0.99; 95% confidence interval = 0.55-1.79). When the analysis was restricted to urban areas, we found that hay fever, symptoms of allergic rhinitis, wheezing, sensitization against pollen, house dust mites or cats, and milk or eggs were associated with outdoor NO2. The results indicate that traffic-related air pollution leads to increased prevalence of atopic sensitizations, allergic symptoms, and diseases.

Child↗
PubMed1999

Rhinosinusitis and atopy in patients infected with HIV.

HYPOTHESIS: Rhinosinusitis is common during HIV infection; its prevalence is uncertain and could probably be related to clinical features, immunoallergological status, and diagnostic criteria METHODS: Seventy-four patients hospitalized with HIV infection were prospectively evaluated for the presence of rhinosinusitis based on clinical findings, nasal endoscopy, or paranasal sinus computed tomography (CT). Immune status, nasal smear, features of atopy (based on the prick test), and its contribution to sinusal inflammatory pathology were also evaluated. RESULTS: Most patients were severely immunosuppressed: CD4+ 155+/-201 cells/mL and 12+/-11% (mean +/- SD). Thirty-five percent of the patients presented at least two criteria of rhinosinusitis (clinical findings, nasal endoscopy, and CT: 35%; clinical findings and CT: 50%; nasal endoscopy and CT: 15%). CT scan showed multiple sinus involvement, opacification over 25% of the total volume of the maxillary sinus in 50% of patients, and opacification of the sphenoidal sinus in 40% of cases. Atopy was present in 18% of patients, a figure which reflects the expected prevalence in our geographic area. Two independent predictors were associated with a higher probability of rhinosinusitis: bilateral absence of maxillary infundibular patency (odds ratio, 7.5; 95% CI = 2.03-27.9) and low total count (odds ratio, 0.99; 95% CI = 0.99-1.00) or percentage of CD4+ (odds ratio, 0.93; 95% CI = 0.88-1.00). CONCLUSIONS: There is a high prevalence of rhinosinusitis in HIV-infected individuals. This finding is related to a decreased cellular immunity, but it does not appear to be related to IgE-related immediate hypersensitivity. Nasal endoscopy should be the first-step diagnostic test. However, when clinical suspicion exists and endoscopy fails to explain symptoms, CT scan is a valuable adjunct to establish this diagnosis.

AIDS-Related Opportunistic Infections↗
PubMed2002

Endotoxin, atopy and asthma.

Endotoxin is infamous for its ability to exacerbate existing allergy and asthma symptoms. Current research supports this phenomenon, demonstrating its significance in the home, as well as in the workplace. At the same time, evidence is emerging that exposure to endotoxin may drive immune development away from the T-helper lymphocyte type 2-mediated allergy and asthma profile. This fits in nicely with the 'hygiene hypothesis', which attributes the past century's rise in allergy and asthma to a reduction in microbial burden. Indeed, infections have been associated with less atopy and asthma. Recent investigations have suggested that naturally-occurring non-infectious exposure to microbial components such as endotoxin might mitigate atopy and asthma as well.

Air Pollution, Indoor↗
PubMed2003

Environmental exposure to endotoxin and other microbial products and the decreased risk of childhood atopy: evaluating developments since April 2002.

PURPOSE OF REVIEW: The hygiene hypothesis proposes an association between the change in exposure to microbes and the increased incidence of atopic diseases in recent decades. Exposure to microbes and childhood infections and their association with atopy has thus attracted much scientific interest. This review focuses on new developments in the field of epidemiology. RECENT FINDINGS: Studies in adults confirm that exposure to orofaecal pathogens are associated with less asthma and allergies. In seropositive individuals, no increase in allergy prevalence over time was noted. Similarly, the generational increase in atopy and allergic rhinitis was not observed in individuals who were exposed to a farming environment in childhood. More than 20 studies have been published examining the effect of exposure to a farm environment in children and adults. Most consistently, the 'protective' farm effect was related to livestock farming and thus to microbial exposure. A dose-dependent inverse relationship between exposure to endotoxin in the mattress dust of children and the occurrence of atopic diseases was shown in rural environments in Europe. In addition, the blood cells of farmers' children were shown to express higher amounts of innate immunity receptors. Only a few farm studies have so far included an objective measure of the microbial environment. The examined exposure to endotoxin might partly be a surrogate measure of a much broader spectrum of immunomodulatory microbial compounds present in a rural environment. SUMMARY: The 'hygiene hypothesis' has gained much credibility, but the results should be balanced against the benefits of established hygiene standards.

Adult↗
PubMed1979

Geographic tongue--a manifestation of atopy.

One hundred patients with geographic tongue have been studied for evidence of an association with atopy. There was a significantly high frequency of personal and/or family history of asthma, eczema and hay fever amongst the patients when compared to a control population. A raised total serum IgE( greater than or equal to 200 u/ml) was significantly more frequent in patients compared to a control population. These findings confirm the impression that in some patients geographic tongue is a sign of atopy.

Adolescent↗
PubMed1986

Associations between asthma history, atopy, and non-specific bronchial responsiveness in young adults.

In 105 subjects taken from a student population and aged between 15 and 30 there was a strong positive association between the presence of the atopic state, defined by skin tests, and a high level of non-specific bronchial responsiveness to methacholine (chi 2 = 10.5, d.f. = 2, P = 0.01). Regression analysis showed a history of asthma, and the symptom of wheeze, to be predominantly predicted by the degree of bronchial responsiveness (R2 = 31%), with only a minor independent contribution from the degree of atopy (R2 a further 5%). The genetic or other reasons for the association between bronchial responsiveness and atopy may have importance in understanding the aetiology of allergic asthma.

Adolescent↗
PubMed1988

Prevalence of atopy is unrelated to presence of inflammatory bowel disease.

The prevalence of atopy (assessed by prick testing and serum IgE measurement), and of symptoms associated with atopy, has been defined in 122 patients with inflammatory bowel disease (IBD) and 103 age-matched controls. History analysis for atopic symptoms, and serum IgE levels, showed no differences between controls and IBD patients, or IBD subgroups (Crohn's disease, ulcerative colitis, ulcerative proctitis). Both in controls and in IBD patients, the prevalence of positive skin tests was higher in young people (aged less than 30) than in others; taking account of age distribution within the groups, there were no differences between controls and IBD patients, or subgroups, in the prevalence of positive skin tests. Our finding do not support the hypothesis that reaginic hypersensitivity plays a significant role in the pathogenesis of IBD.

Adolescent↗
PubMed1988

Influence of atopy on the clinical manifestations of coronavirus infection in adult volunteers.

In an attempt to understand the relationship between viral upper respiratory tract infection and the underlying virological and immunological mechanisms, thirty-four volunteers were inoculated intranasally with coronavirus 229E; subsequent virus shedding and/or antibody rises, indicating active infection, were observed in twenty-nine. There was a greater increase in independently measured scores of clinical severity, e.g. cold symptoms, in those with detectable IgE in nasal secretions (P less than 0.01). A similar association was found between clinical scores and serum IgE concentrations greater than or equal to 150 IU/ml, but the relationship with systemic atopy, as assessed by skin-prick tests to common allergens, was less marked. A more detailed study of twelve of the infected volunteers failed to explain these findings on the basis of mast cell mediator release, as concentrations of leukotriene B4, the sulphidopeptide leukotriene C4, and histamine, were not appreciably elevated in the nasal secretions following virus inoculation. Similarly, there was no evidence that circulating coronavirus specific IgE was produced. Thus, this study suggest that atopy may be related to the severity of cold symptoms produced by coronavirus 229E, although the exact connection has yet to be determined.

Adolescent↗
PubMed2004

RNA editing of interleukin-12 receptor beta2, 2451 C-to-U (Ala 604 Val) conversion, associated with atopy.

BACKGROUND: The production of IgE in B lymphocytes is down-regulated by IFN-gamma. IL-12 induces IFN-gamma production by T lymphocytes and natural killer cells by binding to its specific receptor. RNA editing is a post-transcriptional modification. OBJECTIVE: Here we show that the RNA editing of IL-12 receptor (R) beta2 is associated with atopy. METHODS: Atopic patients and non-atopic healthy controls were studied. Fragments of IL-12R beta2 cDNA and genomic DNA were amplified and sequenced. Furthermore, the function of the IL-12R beta2 chain was investigated. RESULTS: Sequence analysis of the cDNA clones representing IL-12R beta2 mRNA transcripts revealed a C-to-U conversion at nucleotide 2451 (Ala 604 Val) on exon 13 in some atopic patients. Surprisingly, sequence analysis of their genomic DNA showed no 2451 C-to-T (Ala 604 Val) mutation. We concluded that the observed C-to-U mismatch in the cDNA clone is due to a post-transcriptional modification, RNA editing. The C-to-U conversion was observed in 21 (20.6%) of 102 atopic patients, whereas this conversion was observed in only 4 (3.8%) of 104 non-atopic subjects (P<0.001). IFN-gamma production by peripheral blood mononuclear cells (PBMCs) stimulated with IL-12 in the subjects with the C-to-U conversion was significantly lower than that in the subjects without the C-to-U conversion. In atopic patients with the C-to-U conversion, PBMCs faintly showed the tyrosine phosphorylation of Stat4, and the IgE production by PBMCs was not suppressed by IL-12 whereas it was suppressed by IFN-gamma. CONCLUSIONS: The RNA editing of IL-12R beta2, 2451 C-to-U (Ala 604 Val) conversion causes impairment of the IL-12 signal cascade and the subsequent reduction in IFN-gamma production, resulting in the impaired down-regulation of IgE production. This is the first report indicating that atopy is associated with RNA editing.

Case-Control Studies↗
PubMed2004

A functional polymorphism in the promoter region of the cyclooxygenase-2 gene is not associated with asthma and atopy in an Australian population.

BACKGROUND: Cyclooxygenase (COX)-2 is a key inducible enzyme that regulates the production of anti-inflammatory prostaglandin E(2). A single-nucleotide polymorphism, -765G>C, located within a stimulatory protein-1 binding site in the COX-2 promoter region, has been shown to have significantly lower promoter activity in vitro compared with the wild-type and was associated with decreased plasma levels of C-reactive protein after coronary artery bypass surgery. We hypothesized that this polymorphism, which may result in decreased COX-2 transcription, could be associated with more severe asthma, and/or aspirin-intolerant asthma (AIA). OBJECTIVE: To determine the association between the -765G>C COX-2 polymorphism and asthma, disease severity and AIA in a large, well-phenotyped Australian population. METHODS: PCR and restriction fragment length polymorphism analysis was used to characterize the polymorphism in an Australian Caucasian population of patients with mild (n=322), moderate (n=254) or severe (n=88) asthma and in non-asthmatic control subjects (n=512), as well as in patients with AIA (n=58). Genotype and allele association analyses were performed using chi(2) tests. RESULTS: The polymorphic -765C allele was present in approximately 30% of asthmatic patients and non-asthmatic controls. There was no association between the -765G>C polymorphism and asthma (P=0.920), disease severity (P=0.840), atopy (P=0.655) or AIA (P=0.841) in this population. CONCLUSION: Although the -765G>C polymorphism may have lower promoter activity and result in decreased COX-2 expression, it is not associated with asthma, disease severity, AIA or atopy in this Australian population.

Adult↗
PubMed2005

Childhood atopy and allergic disease and skin test responses to environmental mycobacteria in rural Crete: a cross-sectional survey.

BACKGROUND: Through its powerful immunoregulatory effects, infection with atypical mycobacteria may exert a protective effect on the development of childhood allergic disease. OBJECTIVE: To examine the relationship between childhood atopy or allergic disease and previous infection with four species of atypical mycobacteria. METHODS: Eight hundred and six children aged 8-18 years and living in rural Crete--most of whom had had previous BCG immunization--underwent skin prick testing with 10 aeroallergens; their parents completed a standardized questionnaire relating to allergic disease. No less than 8 weeks later each child underwent intradermal skin tests with 0.1 mL solutions of four selected mycobacterial reagents (Aviumin C, Gordonin, Chelonin and Ranin I). RESULTS: Twenty-three percent of children were atopic on skin prick testing; far fewer had symptoms of asthma (5%) or hayfever in conjunction with a positive prick test to pollens (2%). Eighty percent of children had positive skin responses to one or more mycobacterial species. Among all children--and those with a BCG scar--there was no association between atopy or allergic symptoms and mycobacterial skin responses; among the few children without a BCG scar however those with positive mycobacterial responses were less likely to be atopic or to report allergic symptoms; these differences were not statistically significant. CONCLUSIONS: Our findings, in a population of BCG-immunized children, do not lend support to the suggestion that infection with atypical mycobacteria is protective against childhood allergic disease.

Adolescent↗
PubMed2006

The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma.

BACKGROUND: The cysteinyl-leukotriene receptor type 1 (CysLT1) mediates the bronchoconstrictor and pro-inflammatory actions of cysteinyl-leukotrienes (LTC4, LTD4, LTE4) in asthma and is the molecular target of the lukast class of oral anti-leukotriene drugs. We screened the CYSLTR1 gene on chromosome Xq13-21 for coding region polymorphisms, and investigated their associations with allergy and asthma. METHODS: Solid-phase chemical cleavage was used to screen polymorphisms in the coding region of CYSLTR1. A TaqMan allelic discrimination assay was used to genotype a 927T/C SNP and oligonucleotide ligation assays were used to genotype the previously reported 617T/C and 898G/A SNPs of CYSLTR1 in 341 asthmatic families from the UK. Associations with asthma diagnosis, atopic status, serum-specific IgE and severity of allergy and asthma were examined. RESULTS: Family-based association tests showed that the 927 T allele was associated with atopy severity, especially in female subjects, but not with asthma diagnosis or severity, atopic status, bronchial hyper-responsiveness to methacholine or forced expiratory volume in 1 s. CONCLUSION: Mutation screening identified only one polymorphism, 927T/C, in the coding region of the CysLT1 receptor. This polymorphsim is predictive of atopy severity, but not associated with asthma.

Adolescent↗
PubMed2004

A case of fatal systemic toxoplasmosis in a cat being treated with cyclosporin A for feline atopy.

Acute systemic toxoplasmosis was diagnosed in a 4-5-year-old, male, Domestic Short Hair cat, which had been on cyclosporine A immunomodulatory therapy for feline atopy, over an 8-month period. Cyclosporin A (CsA) has shown promising results as a immunosuppressive agent in the cat for the treatment of eosinophilic plaque and granulomas, allergic cervico-facial pruritus, feline atopy and other immune-mediated dermatoses. However, inhibition of T-lymphocyte function by CsA is believed to have predisposed this cat to the development of a newly acquired, acute Toxoplasma gondii infection, as characterized by severe hepatic and pancreatic pathology in conjunction with the heavy parasite load demonstrated on immunohistochemical (IHC) stains for T. gondii. Cats on CsA therapy appear to be at risk of developing fatal systemic toxoplasmosis.

Animals↗
PubMed1990

Atopy and systemic reactions to drugs.

To elucidate whether systemic reactions (SR) to drugs should be included in the atopic status in epidemiological studies, we compared the distribution of atopy in subjects with or without a history of SR to drugs. The studied population comprised 2067 adults, 20 to 60 years old, visiting a health care center for a check-up examination. The protocol included a questionnaire related to history of SR to drugs and a Phadiatop test which evaluates on a blood sample the presence of specific IgE against common aeroallergens. Overall, 14.7% of the study group, including 66% women, reported reliable histories of SR to drugs. The cumulative prevalence of asthma, hay fever and childhood dermatitis was higher in the SR group. By contrast, the percentage of positive Phadiatop tests was similar in subjects with or without a history of SR. Thus atopy, defined by an objective criterion, i.e. the presence of specific IgE against common aero-allergens, is not associated with the occurrence of SR to drugs. Such a history should not be included as part of the atopic status.

Adult↗
PubMed1991

Association of features of atopy and diagnostic parameters in hymenoptera venom allergy.

In a total of 525 patients with hypersensitivity reactions to hymenoptera stings diagnostic parameters of hymenoptera venom (HV) allergy (severity of reactions, skin test threshold and RAST for bee and vespid venoms) were investigated for their relationship to the following indicators of atopy: positive history of atopic diseases, elevated (less than or equal to 100 kU/l) total serum IgE and positive prick test reactions to common inhalant allergens (CIA) (grass pollen, cat epithelium, house dust mite). There was a conclusive history of atopic disease in 25%, a total serum IgE greater than or equal to 100 kU/l in 48%, and at least one positive reaction to CIA in 53%. Total IgE greater than or equal to 100 kU/l correlated with a higher frequency of RAST classes greater than or equal to 2 (P less than 0.01) and with less severe reactions to hymenoptera stings (P less than 0.05). In the presence of at least one positive reaction to CIA, there were more frequently skin test thresholds less than or equal to 10 micrograms/ml (P less than 0.05) and RAST classes greater than or equal to 2 (P less than 0.01) for HV than in CIA prick test negative individuals. There was no significant, relationship between the other pairs of parameters evaluated. Thus, reactivity to HV in diagnostic tests is increased in the presence of certain indicators of atopy. This has to be considered in the interpretation of skin test and RAST results obtained with HV.

Adolescent↗