Erratum: Allergen specific exposure associated with high immunoglobulin E and eye rubbing predisposes to progression of keratoconus.
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PROVIDER: S-EPMC5549429 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:Prior findings linking allergy and cancer have been inconsistent, which may be driven by diverse assessment methods. We used serum specific immunoglobulin E (IgE) against common inhalant allergens that was assessed prior to cancer diagnosis in studying this association. We selected 8,727 Swedish men and women who had measurements of serum allergen-specific IgE and total IgE between 1992 and 1996. Multivariable Cox regression using age as a timescale was performed to assess the associations of IgE sensitization, defined by any levels of serum specific IgE ≥35 kU/L, with risk of overall and specific cancers. A test for trend was performed by assigning scores derived from allergen-specific IgE levels at baseline as an ordinal scale. Kaplan-Meier curves and log-rank test were used to assess cancer survival by IgE sensitization status. During a mean follow-up of 16 year, 689 persons were diagnosed with cancer. We found an inverse association between IgE sensitization and cancer risk, with a hazard ratio (HR) of 0.83 and 95% confidence intervals (CI) of 0.70-0.99. A similar trend was seen with specific IgE scores overall (Ptrend = 0.007) and in women (Ptrend = 0.01). Although IgE sensitization was not associated with risk of common site-specific cancers, serum specific IgE scores were inversely associated with melanoma risk in men and women combined, and with risk of female breast and gynecological cancers combined. No association with survival was observed. The association between circulating IgE levels and incident cancer may point toward a role of T-helper 2 (TH2)-biased response in development of some cancers.
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Project description:BackgroundExposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEPs), increases the risk of asthma and asthma exacerbation; however, the underlying mechanisms remain poorly understood.ObjectiveWe sought to examine the effect of DEP exposure on the generation and persistence of allergen-specific memory T cells in asthmatic patients and translate these findings by determining the effect of early DEP exposure on the prevalence of allergic asthma in children.MethodsThe effect of DEPs on house dust mite (HDM)-specific memory responses was determined by using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort were analyzed to determine the effect of DEP exposure on asthma outcomes.ResultsDEP coexposure with HDM resulted in persistent TH2/TH17 CD127(+) effector/memory cells in the lungs, spleen, and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased TH2 cytokine levels in mice that had been previously exposed to both HDM and DEPs versus those exposed to HDM alone. On the basis of these data, we examined whether DEP exposure was similarly associated with increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort. Early-life exposure to high DEP levels was associated with significantly increased asthma prevalence among allergic children but not among nonallergic children.ConclusionThese findings suggest that DEP exposure results in accumulation of allergen-specific TH2/TH17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma.
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Project description:IntroductionAllergen-specific immunoglobulin isotype formation associated with immunoglobulin class-switching during the lactation period is the immunological background for food allergy in infants. We analyzed the serial changes in the production of feeding type-related egg- and milk-specific immunoglobulin isotypes from birth to 6 months of age with or without eczema in 84 infants.MethodsAllergen-specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA, and IgE levels of hen's egg and bovine milk were measured in cord blood and blood samples from infants at 2, 4, and 6 months of age by the densely carboxylated protein microarray.ResultsFormula and mixed feeding were associated with a rapid increase in cow's milk allergen-specific immunoglobulins and feeding type-related significant differences in casein-specific immunoglobulin levels were detected. Breast and mixed feeding were associated with slow but significant increase in ovalbumin-specific IgG1 and IgE levels, but not other immunoglobulins. We found two different immunoglobulin isotype formation at 6 months of age with low- or high-affinity IgE against ovalbumin. One isotype formation pattern had relatively high ovalbumin-specific IgG1 levels, detectable IgG2, and low-affinity IgE, while the other had low ovalbumin-specific IgG1 levels, undetectable IgG2, and high levels of high-affinity IgE. The incidence of eczema was significantly higher in the latter pattern (84.6%), compared with the remaining infants (42.2%).ConclusionsFeeding practice-related allergen sensitization and immunoglobulin isotype formation were identified during the lactation period. The development of eczema during the lactation period could potentially modify the immunoglobulin isotype formation with high levels of high-affinity IgE.
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Project description:BackgroundAllergen exposure via the respiratory tract and in particular via the nasal mucosa boosts systemic allergen-specific IgE production. Intranasal corticosteroids (INCS) represent a first line treatment of allergic rhinitis but their effects on this boost of allergen-specific IgE production are unclear.AimHere we aimed to determine in a double-blind, placebo-controlled study whether therapeutic doses of an INCS preparation, i.e., nasal fluticasone propionate, have effects on boosts of allergen-specific IgE following nasal allergen exposure.MethodsSubjects (n = 48) suffering from grass and birch pollen allergy were treated with daily fluticasone propionate or placebo nasal spray for four weeks. After two weeks of treatment, subjects underwent nasal provocation with either birch pollen allergen Bet v 1 or grass pollen allergen Phl p 5. Bet v 1 and Phl p 5-specific IgE, IgG1-4, IgM and IgA levels were measured in serum samples obtained at the time of provocation and one, two, four, six and eight weeks thereafter.ResultsNasal allergen provocation induced a median increase to 141.1% of serum IgE levels to allergens used for provocation but not to control allergens 4 weeks after provocation. There were no significant differences regarding the boosts of allergen-specific IgE between INCS- and placebo-treated subjects.ConclusionIn conclusion, the application of fluticasone propionate had no significant effects on the boosts of systemic allergen-specific IgE production following nasal allergen exposure.Trial registrationhttp://clinicaltrials.gov/NCT00755066.
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Project description:PurposeTo investigate corneal sensitivity to selective mechanical, chemical, and thermal stimulation and to evaluate their relation to dry eye symptoms in patients with keratoconus.MethodsCorneal sensitivity to mechanical, chemical, and thermal thresholds were determined using a gas esthesiometer in 19 patients with keratoconus (KC group) and in 20 age-matched healthy subjects (control group). Tear film dynamics was assessed by Schirmer I test and by the non-invasive tear film breakup time (NI-BUT). All eyes were examined with a rotating Scheimpflug camera to assess keratoconus severity.ResultsKC patients had significatly decreased tear secretion and significantly higher ocular surface disease index (OSDI) scores compared to controls (5.3±2.2 vs. 13.2±2.0 mm and 26.8±15.8 vs. 8.1±2.3; p<0.001). There was no significant difference in NI-BUT between the two groups (KC: 9.8±4.8 vs. control: 10.7±3.8; p>0.05). The mean threshold for selective mechanical (KC: 139.2±25.8 vs. control: 109.1±24.0 ml/min), chemical (KC: 39.4±3.9 vs. control: 35.2±1.9%CO2), heat (KC: 0.91±0.32 vs. control: 0.54±0.26 Δ°C) and cold (KC: 1.28±0.27 vs. control: 0.98±0.25 Δ°C) stimulation in the KC patients were significantly higher than in the control subjects (p<0.001, for all parameters). No correlation was found between age and mechanical, chemical, heat or cold thresholds in the patients with KC (p>0.05), whereas in the control subjects both mechanical (r = 0.52, p = 0.02), chemical (r = 0.47, p = 0.04), heat (r = 0.26, p = 0.04) and cold threshold (r = 0.40, p = 0.03) increased with age. In the KC group, neither corneal thickness nor tear flow, NI-BUT or OSDI correlated significantly with mechanical, chemical, heat or cold thresholds (p>0.05 for all variables).ConclusionsCorneal sensitivity to different types of stimuli is decreased in patients with keratoconus independently of age and disease severity. The reduction of the sensory input from corneal nerves may contribute to the onset of unpleasant sensations in these patients and might lead to the impaired tear film dynamics.
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Project description: Not available
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Project description:BackgroundGenetic, epidemiologic, and clinical evidence suggests that, in horses, there are manifestations of hypersensitivity that can occur together.ObjectivesTo investigate whether concurrent insect bite hypersensitivity (IBH) and severe equine asthma (EA) is associated with higher allergen-specific and total serum immunoglobulin E (IgE) concentrations than only EA or IBH.AnimalsHealthy control horses (C, n = 40), horses with IBH (IBH, n = 24), severe EA (EA, n = 18), and both conditions (IBH/EA, n = 23) were included.MethodsIn our retrospective comparative study, sera from horses with signs of severe EA, IBH, and control animals were used. IgE specific for 15 recombinant (r) allergens as well as total serum IgE concentrations were measured by enzyme-linked immunosorbent assay.ResultsGroup IBH (median sum r-Culicoides IgE: optical density at 405 nm [OD405 ] = 3.54 [0.48-15.07]) and group IBH/EA (OD405 = 4.55 [0.46-17.15]) had significantly (P < .001) higher IgE against Culicoides r-allergens than groups C (OD405 = 0.44 [0.21-2.05]) and EA (OD405 = 0.6 [0.2-2.9]). There were no significant (P > .05) differences between group IBH and group IBH/EA. No significant differences among the groups were found for the other r-allergens or total serum IgE concentration. Compared to controls, horses with severe IBH had significantly increased IgE concentration to 5 Culicoides r-allergens (P < .05), whereas horses with moderate IBH had significantly increased IgE concentration to only 3 Culicoides r-allergens (P < .05).Conclusions and clinical importanceSusceptibility of IBH-affected horses to develop EA is likely not associated with IgE-mediated immune reactions but with other immunopathological mechanisms.
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Project description:BackgroundTo explore current eye care practice in keratoconus diagnosis and management in Kenya.MethodsAn online questionnaire was distributed to ophthalmic clinical officers (OCO) and optometrists.ResultsA total of 203 responses were received from 52 OCOs and 151 optometrists with a response rate of 24.4% and 53.5% respectively. The majority reported having access to retinoscopes (88.5%; p = 0.48) and slit lamps (76.7; p = 0.14). Few practitioners had access to a corneal topographer (13.5%; p = 0.08) and rigid contact lens (CL) fitting sets (OCOs 5.8%, optometrists 33.8%; p < 0.01). One-third did not feel that retinoscopy (38.7%; p = 0.21), slit lamp findings (30.3%; p = 0.10) and corneal topography (36.6%; p = 0.39) are important investigations in keratoconus diagnosis. Corneal topography was not recommended in two-thirds of patients (59.0%; p = 0.33) with vernal keratoconjunctivitis (VKC). The majority counselled against eye rubbing in mild (73.6%; p = 0.90) VKC, 52.9% in moderate (p = 0.40) and 43.6% in severe (p = 0.24) cases. The majority prescribed spectacles in mild (90.2%; p = 0.95), 29% (p = 0.97) in moderate and 1.9% (p = 0.05) in severe cases. When the binocular best corrected visual acuity (BCVA) with spectacles was ≤ 6/18, 76.9% of OCOs and 58.9% of optometrists referred for CLs (p = 0.02). When binocular BCVA with CLs dropped to ≤ 6/18, 83.7% (p = 0.18) referred to the ophthalmologist for surgical intervention. Few OCOs fitted rigid CLs (15.4% OCOs, 51.0% optometrists; p = 0.01), majority referred to optometrists (82.7% OCOs, 43.7% optometrists; p < 0.01). Progression was monitored in 70.1% (p = 0.11) of mild, 50.9% (p = 0.54) moderate and 25.3% (p = 0.31) advanced cases. Few OCOs (15.4%) performed corneal cross-linking (CXL). A few respondents (5.4%; p = 0.13) did not know when to refer keratoconus patients for CXL. Co-management with ophthalmologists was reported by 58.0% (p = 0.06) of respondents.ConclusionThe results of this study highlight the need to map services for keratoconus patients, review current curricula and continuous education priorities for mid-level ophthalmic workers, develop guidelines for the diagnosis and management of keratoconus and improve interdisciplinary collaboration.
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Project description:BackgroundAllergic diseases are some of the most common diseases worldwide. Genome-wide association studies (GWASs) have been conducted to elucidate the genetic factors of allergic diseases. However, no GWASs for allergen component sensitization have been performed.ObjectiveWe sought to detect genetic variants associated with differences in immune responsiveness against allergen components.MethodsThe participants of the present study were recruited from the Tokyo Children's Health, Illness, and Development study, and allergen component-specific IgE level at age 9 years was measured by means of allergen microarray immunoassays. We performed GWASs for allergen component sensitization against each allergen (single allergen component sensitization, number of allergen components analyzed, n = 31), as well as against allergen protein families (allergen protein group sensitization, number of protein groups analyzed, n = 16).ResultsWe performed GWAS on 564 participants of the Tokyo Children's Health, Illness, and Development study and found associations between Amb a 1 sensitization and the immunoglobulin heavy-chain variable gene on chromosome 14 and between Phl p 1 sensitization and the HLA class II region on chromosome 6 (P < 5.0 × 10-8). A GWAS-significant association was also observed between the HLA class II region and profilin sensitization (P < 5.0 × 10-8).ConclusionsOur data provide the first demonstration of genetic risk for allergen component sensitization and show that this genetic risk is related to immune response genes including immunoglobulin heavy-chain variable gene and HLA.
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Project description:AimPaediatric cut-off values for serum allergen-specific IgE (sIgE) using the Siemens IMMULITE(®) 2000 system to diagnose allergic rhinoconjunctivitis have not been established. We aimed to determine cut-off levels for sIgE for 10 common inhalant allergens and to study the relationship between sIgE, total IgE and fractional exhaled nitric oxide (FENO ).MethodsWe enrolled 243 schoolchildren, including 164 with allergic rhinoconjunctivitis. Parental interviews, skin prick tests, sIgE, total IgE, FENO measurements, spirometry and exercise tests were performed.ResultsCut-off values with the best combined sensitivity and specificity were above the detection limit of the assay for seven of the ten allergens (0.23-1.1 kU/L). The overall accuracy of the IMMULITE(®) in detecting allergic rhinoconjunctivitis was good. sIgE was superior to total IgE and FENO in predicting allergic rhinoconjunctivitis to timothy, birch, mugwort, cat, dog and house dust mite. FENO was elevated in children with allergic rhinoconjunctivitis, irrespective of asthma.ConclusionCut-off values for sIgE were dependent on the allergic phenotype and were above the IMMULITE(®) detection limit for seven of ten inhalant allergens. Consequently, using the detection limit for sIgE as the decision point would result in over-diagnosing allergic rhinoconjunctivitis. When measuring elevated FENO in children, allergic rhinoconjunctivitis should be suspected.
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