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Background: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile., Methods: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented., Results: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions., Conclusions: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients., (© 2021 S. Karger AG, Basel.)

Only few data on safety during high-dose, accelerated escalation schedules during subcutaneous allergen immunotherapy (AIT) are available. The aim of this study was to assess the safety and tolerability of an accelerated dose escalation schedule of AIT in adult patients with moderate to severe seasonal rhinoconjunctivitis in a multicenter, open-label, randomized phase II trial. The dose escalation scheme for patients in Group I (1 strength) included 3 injections with 1 strength, B (10,000 TU/mL), whereas the dose escalation scheme for Group II (standard) included 7 injections with 2 strengths, A (1,000 TU/mL) and B (10,000 TU/mL), of an aluminum hydroxide-adsorbed allergoid grass pollen preparation. Overall, 72 of 87 randomized patients (83.7%) reported at least 1 treatment-emergent adverse event (TEAE; 82.2 [Group I] vs. 85.4% [Group II]); 58.8% of all reported TEAEs were assessed as being related to AIT (60.0 vs. 48.8%). The most frequently reported AIT-related TEAEs were swelling (46.7 vs. 34.1%), erythema (28.9 vs. 36.6%), and pruritus (31.1 vs. 17.1%) at the site of the injection. Systemic allergic reactions occurred in 5 (5.8%) patients overall, with more being reported in the 1-strength group (4 [8.9%] vs. 1 [2.4%]). All systemic allergic reactions were classified as World Allergy Organization (WAO) Grade 1 or Grade 2 reactions. Accelerated high-dose escalation with an aluminum hydroxide-adsorbed grass pollen allergoid can be initiated with a safety and tolerability profile comparable to the standard dose escalation schedule in patients with allergic rhinitis with or without asthma., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background: Recent studies have proposed that clinical and immunological differences exist between mono- and poly-sensitized subjects with allergic diseases, and poly-sensitization was related to multimorbidity of allergic diseases among children and adolescents., Objective: We compared the clinical characteristics and multimorbidity of allergic diseases between adult rhinitis patients mono- and poly-sensitized to common aeroallergens using a retrospective cross-sectional study for tertiary care subjects., Methods: The medical records of 1,615 patients who were clinically diagnosed with rhinitis by an otolaryngologist and evaluated with skin prick tests were reviewed. The severity of the rhinitis symptoms, comorbidities (asthma, conjunctivitis, and eczema), family history of allergic diseases, and the results of skin prick tests were evaluated., Results: There were 392 patients with mono-sensitized rhinitis (mono-sR), 325 with poly-sensitized rhinitis (poly-sR), and 898 with non-sensitized rhinitis (non-sR). Comorbid conjunctivitis and eczema were most common in poly-sR, followed by mono-sR, and least common in non-sR patients. The age at onset of rhinitis was clearly different between adult patients with non-sR and mono-/poly-sR, but not between patients with mono-sR and poly-sR. However, the age at onset of rhinitis was much younger in non-sR and mono-sR patients with conjunctivitis or eczema than those without such comorbidities., Conclusion: Thefrequency of comorbid conjunctivitis and eczema in adult rhinitis patients differed by a quantitative trait of immunoglobulin E sensitization. Depending on the multimorbidity of allergic diseases, onset age of rhinitis seems to be different in adult rhinitis patients., (© 2020 S. Karger AG, Basel.)

Background: Transient receptor potential ankyrin 1 (TRPA1) is an ion channel known to mediate nociception and neurogenic inflammation, and to be activated by reactive oxygen and nitrogen species (ROS and RNS) produced at the sites of inflammation. Because neurogenic inflammation as well as the release of ROS and RNS are typical features of early stages of allergic responses, we hypothesized that TRPA1 may be involved in triggering and/or amplifying allergic inflammation., Objective: This study aims at exploring the role of TRPA1 ion channel in acute ovalbumin-induced allergic inflammation in applicable murine models., Methods: The effects of pharmacological blockade and genetic deletion of TRPA1 in ovalbumin-induced allergic conjunctivitis and acute paw inflammation were studied in mice sensitized to ovalbumin., Results: Ovalbumin-induced allergic conjunctivitis was milder in TRPA1-deficient mice and alleviated in wild-type mice treated with the TRPA1 antagonist TCS 5861528. Subcutaneous challenge with ovalbumin caused a significant paw edema and interleukin (IL)-4 production in sensitized mice; these responses were attenuated in animals treated with the TRPA1 antagonist and in TRPA1-deficient mice. Interestingly, blockade of the major secondary effector of TRPA1, substance P, also resulted in attenuated ovalbumin-induced paw edema and IL-4 production. However, the splenocytes' responses to ovalbumin were similar in cells from wild-type and TRPA1-deficient mice sensitized to ovalbumin., Conclusion: These results introduce a novel concept that TRPA1 mediates early events in allergic inflammation, but does not seem to affect allergic sensitization, and could therefore be a novel drug target to treat conditions associated with allergic inflammation., (© 2019 S. Karger AG, Basel.)

Background: Liposomal eye spray (LS) has been introduced for the treatment of dry eye. Whether LS can also relieve symptoms due to allergic rhinoconjunctivitis (ARC) has not yet been sufficiently investigated., Objectives: The aim of this study was to assess the onset of action, the reduction of allergy symptoms, and the safety of LS - a nonpharmacological treatment option - compared with those of antihistamine eye drops (AD)., Methods: In this open, prospective, controlled, monocenter noninterventional study, adults with ARC received either LS or AD for the relief of eye irritation after a positive conjunctival provocation test (CPT). All patients completed a questionnaire before and after the CPT. Eye irritation was rated on a visual analogue scale (VAS) at 6 time points. Conjunctival redness was analyzed using objective digital analysis based on images taken during the study visit., Results: Data were collected from 40 patients (20 per group). In both groups, 80% of patients perceived an onset of action within 0-2 min after application of LS or AD following the CPT. Relief of eye irritation (as determined by VAS) increased throughout the visit for both groups. In the digital analysis, the mean proportion of redness of the eye decreased from 10.3 to 7.0% for LS and from 10.4 to 6.5% for AD, with the largest difference observed 10 min after application (LS: 8.9%; AD: 6.0%; p = 0.094)., Conclusions: LS is a nonpharmacological treatment option for ARC, showing no significant difference or relevant numerical inferiority to AD in any parameter studied. It was generally safe and well tolerated., (© 2019 S. Karger AG, Basel.)

Background: Early pollen flight and new allergens prolonging the pollen season means that the time for up-dosing of allergen-specific subcutaneous immunotherapy (SCIT) outside the pollen season becomes shorter. Hence, for patients who wish or need to be up-dosed faster, an accelerated induction regimen would provide a useful treatment option., Methods: An accelerated up-dosing regimen (0.1-0.3-0.5 mL at weekly intervals) was compared to conventional up-dosing (0.05-0.1-0.2-0.3-0.4-0.5 mL at weekly intervals) using an allergoid birch pollen SCIT preparation. After up-dosing, the maintenance dose (0.5 mL) was given 3 times at biweekly intervals. The multicenter study was performed according to an open randomized, parallel-group design., Results: A total of 123 birch pollen-allergic patients (81 adults and 42 adolescents) presenting with rhinitis or rhinoconjunctivitis with or without mild asthma (FEV1 >70%) were randomized to either the conventional registered up-dosing or an accelerated regimen. In total, 96.7 and 98.4% successfully reached the maintenance dose for the conventional and accelerated regimen, respectively, without relevant differences between adults and adolescents. Both regimens were safe and well tolerated. Furthermore, significant increases (similar in size) in specific IgG and IgG4 after 3 months of treatment were observed in both groups, independent of age., Conclusion: The accelerated SCIT regimen was revealed to be as safe as the conventional regimen, and the immunological effects of both regimens are similar. Accordingly, the accelerated regimen may be used to up-dose patients of adult as well adolescent age within 2 weeks., (© 2017 S. Karger AG, Basel.)

Background: Allergic reactions in patients with seasonal or perennial rhinoconjunctivitis mediated by airborne allergens can be effectively assessed with the conjunctival provocation test (CPT). The CPT is a fast and easy diagnostic procedure that challenges the ocular mucosa with instillations of allergen solutions into the conjunctival region. This paper aimed to investigate the possible influence of repeated diagnostic CPT procedures on the patient's clinical presentation, i.e. to analyze desensitization effects caused by diagnostic solutions and to show the reproducibility of CPT results., Methods: Treatment progress in 120 placebo-treated patients from 2 immunotherapeutic dose-finding studies was estimated and documented, as based on the CPT which was applied at 4 visits with intervals of 4, 8 and 16 weeks. High-resolution digital photos collected as part of the CPT documentation were analyzed by an external observer and by digital analysis software to determine conjunctival redness, completely independent of the subjectivity of investigators and patients., Results: Two extremal scenarios of the redness changes were considered after provocation with 10,000 standard quality units/ml. A maximal decrease of about 3% (t test: p = 0.0002; U test: p = 0.001) and a minimal decrease of about 1% (t test: p = 0.254; U test: p = 0.431) were found., Conclusions: The observed decrease in conjunctival hyperemia can be explained by local desensitization or by placebo effect. Due to the setup of both studies considered, we could not ascertain how these factors influence the decrease in redness. In order to attribute the observed effects to local conjunctival desensitization with certainty, further pilot studies are needed., (© 2016 S. Karger AG, Basel.)

Background: Massive B cell lymphoid hyperplasia and its associated factors may play a role in exacerbating inflammation in allergic disorders. We here investigated the chemokines and CD4-positive T cell subset involved in the development of secondary lymphoid follicles (iCALT) in conjunctival tissues in an atopic keratoconjunctivitis mouse model (AKC mouse)., Methods: NC/Nga mice were divided into three groups: AKC (percutaneous sensitization and instillation of crude house dust mite antigen), AD (percutaneous sensitization only) and C (untreated control). Pathological changes in the conjunctival tissues of each group were investigated using histological and immunohistochemical detection of CD4 and CD20. Furthermore, tissue sections of iCALT (AKC-iCALT subgroup) and conjunctiva without iCALT (AKC-conjunctiva subgroup) were obtained from AKC mice using laser-assisted microdissection. mRNA expression of chemokine and T cell subset-related transcription factors were compared between the AKC-iCALT and AKC-conjunctiva subgroups using polymerase chain reaction (PCR) array and real-time reverse transcription-PCR (RT-PCR) methods., Results: iCALT with central aggregation of CD20-positive B cells and CD4-positive T cell infiltration surrounding B cells was observed in the palpebral conjunctival tissue of the AKC group, but not in that of the AD and C groups. Chemokine and T cell subset-related transcription factor expression was confirmed using real-time RT-PCR, with significant increases in Ccl5, Ccl17, Cxl20, Cxcl3, Ccr7, Foxp3 and T-bet mRNA expression in the AKC-iCALT subgroup compared with those in the AKC-conjunctiva subgroup., Conclusions: We concluded that CCL5, CCL17 and CCL20, as well as T-bet- and Foxp3-positive lymphocytes may be iCALT-related factors and that iCALT-related chemokines are worth evaluating as biomarkers., (© 2015 S. Karger AG, Basel.)

Background: Patients with allergic rhinoconjunctivitis are susceptible to both nasal and ocular symptoms. The conjunctival provocation test (CPT) is an established diagnostic procedure used in allergic rhinoconjunctivitis, particularly to document a patient's current reactivity to allergens. To date, there are no international guidelines defining the CPT. No approved evaluation method exists for interpreting CPT results. This paper aims to establish the digital analysis of macroimages as an objective, validated and standardized method for interpreting CPT results., Methods: In a clinical immunotherapy trial with 155 patients, treatment progress was documented based on the CPT. Local investigators used a symptom score to grade tearing, reddening and the patients' subjective perception of symptoms (mucosal irritation). A central observer rated conjunctival hyperemia via digital photography. Digital image analysis software was utilized to determine conjunctival hyperemia., Results: Spearman's correlation between the local investigators' and the central observer's ratings was r = 0.729 (p < 0.001); the percentage of total agreement was 48% (based on 739 photos). Digital image analysis (based on 48 photos) had a high percentage of total agreement with the central observer's ratings (69%) but a low percentage of total agreement with the investigators' ratings (38%). The corresponding correlations were r = 0.264 and 0.064, respectively., Conclusion: Photography-based rating by a central observer may represent a valuable supplement to the local investigator's assessment for making an objective evaluation of CPT results. Digital image analysis possesses the potential of being an objective evaluation method compared to the wide-spread subjective evaluation by the investigators., (© 2013 S. Karger AG, Basel.)

Background: Most panel studies focusing on rhinitis and conjunctivitis symptoms and birch pollen have been performed on a linear basis and have not included air pollution and meteorological variables as potential confounders. The objective of this panel study was to assess the relationship between symptoms of seasonal allergic rhinoconjunctivitis and daily airborne birch pollen concentrations, checking with adequate statistical tools the shapes of concentration-response curves and controlling for confounders., Methods: The severity of rhinitis, conjunctivitis, and bronchial symptoms was recorded daily in March and April 2010 (3,311 person-days) in 61 seasonal allergic rhinoconjunctivitis patients sensitized to birch. Data were analyzed with generalized additive and generalized estimating equation models to quantify the effects of birch pollens., Results: The relationship between birch pollen and the percentage of patients with nasal, ocular and bronchial symptoms was linear until birch daily average concentrations of, respectively, 110, 70, and 70 grains/m(3); it reached a plateau thereafter. For an increase of 10 grains/m(3), the OR (95% CI) for nasal, ocular, and bronchial symptoms were, respectively, 1.07 (1.03-1.12), 1.17 (1.08-1.27), and 1.12 (1.03-1.21). At the beginning of the season, no nasal or ocular symptoms were observed below a threshold of 30 grains/m(3)., Conclusions: Adequate modeling regression shows that the clinical response to natural exposure to birch pollen in sensitized patients varies during Betula pollen season, with a threshold at the beginning of the season, while over the whole season the relationship is linear for nasal, ocular, and bronchial symptoms up to a saturation point, followed by a plateau., (© 2013 S. Karger AG, Basel.)

Background: Nonpathogenic Escherichia coli strain Nissle 1917 (EcN) has immunomodulatory properties and can act on different cells which are important for the allergic immune response. Herein, we investigated the efficacy and tolerability of EcN in subjects with grass pollen-dependent allergic rhinoconjunctivitis., Methods: Grass pollen-allergic subjects were randomly allocated to receive EcN in a double-blind, placebo-controlled manner. The treatment was performed from 2 months before onset until the end of one grass pollen season (in total: 6 months). The clinical symptom score and the intake of symptomatic medications were assessed. A skin prick test and grass pollen-specific immunoglobulin (Ig) E and IgA were evaluated before and after treatment., Results: Our results show that coseasonal treatment with EcN in grass pollen-allergic subjects was not superior to placebo as assessed using the symptom-medication score (p = 0.257). Interestingly, an increase [median (range)] in grass pollen-specific IgA was detectable in the EcN group [20,556 LU/ml (1,812-60,800)] versus placebo [5,246 LU/ml (944-50,467)] (p = 0.048)., Conclusions: The results indicate that 6 months of coseasonal nonspecific immunomodulation by EcN is not sufficient to achieve clinical efficacy in grass pollen-allergic subjects. Future approaches in which such immunomodulators are combined with an allergen-specific protocol might enhance the clinical efficacy of the allergen-specific treatment., (© 2013 S. Karger AG, Basel.)

Background: Sublingual immunotherapy (SLIT) is a clinically effective treatment in allergic conjunctivitis (AC); however, the mechanism of the underlying pharmacodynamics remains unclear. Here, we investigate the efficacy and the mechanism of a sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine AC model., Methods: A murine model of AC caused by Der f extract was developed in BALB/c mice by repeated application of allergen. Sensitized mice were SLIT treated by Der f drops and subsequently analyzed for AC symptoms, histopathological and immunological parameters., Results: In this study, Der f extract successfully induced the symptoms of AC in BALB/c mice. In these sensitized mice, clinical symptoms (scratching behavior, lacrimation, conjunctival hyperemia and edema), immunological and histopathological findings (inflammatory cell infiltration) were very similar to those in human AC. SLIT treatment of sensitized mice markedly reduced the clinical and histopathological symptoms and decreased the expression levels of total immunoglobulin E (IgE), Der f-specific IgE and T helper cell 2 (Th2) cytokine interleukin-4, with a significant increase in Der f-specific IgG4 and Th1 cytokine interferon-γ., Conclusions: SLIT with Der f drops is a potentially effective means of immunotherapy for Der f-induced AC by modulating the Th2-biased allergic immune response., (Copyright © 2013 S. Karger AG, Basel.)

Background: We performed an in vitro elicitation test to determine the ability of different types of wheat-allergic patients' IgE to induce humanized mast cell activation after the addition of various time-treated acid-hydrolyzed wheat proteins (HWPs)., Methods: The reactivity of heat- and various time-treated acid-hydrolyzed glutens (acid-HGs) and commercial acid-HWP (HWP1), using serum IgE from wheat allergy accompanied by skin and rhinoconjunctival sensitization to HWP1 in the facial soap, pediatric subjects with food allergy to native wheat, adult wheat-dependent exercise-induced anaphylaxis subjects, and nonatopic healthy subjects, was elucidated by dot blot and a luciferase assay-based in vitro elicitation test (EXiLE test)., Results: Serum from subjects sensitized with HWP1 reacted only to acid-HGs (acid-HGs treated for 0.5-3 or 6 h), but not native gluten, in the results of the dot blot. In contrast, sera from pediatric subjects sensitized with native wheat reacted to native gluten more strongly and showed only slight reactions to 0.5- to 1-hour-treated acid-HGs. The results of the in vitro elicitation test showed that acid hydrolyzation of the gluten attenuated antigen-induced luciferase expression in a time-dependent manner for sera from native-wheat-sensitized pediatric subjects. On the other hand, in the sera from HWP1-sensitized subjects, acid hydrolyzation of the gluten for 0.5 h dramatically increased luciferase expression., Conclusions: Even after prolonged hydrolyzation, acid-HGs still retained the ability to activate mast cells in the case of HWP1-sensitized subjects., (Copyright © 2012 S. Karger AG, Basel.)

Background: Seasonal allergic conjunctivitis can manifest itself through tear film instability and symptoms of eye discomfort during the pollen season. This study investigated whether seasonal allergic inflammation defines tear film instability outside the season., Methods: Twenty-three control subjects and 13 ragweed-allergic patients were involved (21 female, 15 male; mean age 26.6 ± 5.4 years). Outside the pollen season, subjective ocular symptoms, non-invasive tear film break-up time, lower tear meniscus height and the tear lipid layer's interference pattern grade were recorded. C3a complement activation level was also measured in collected tear samples., Results: Non-invasive tear film break-up time, lower tear meniscus height, C3a complement activation level and the incidence of the different grades of tear lipid pattern did not differ significantly in the two examined groups (p ≥ 0.223). The mean eye symptom score outside the season was greater in the allergic group, but the difference was not significant (p = 0.062). The C3a complement activation level showed a significant and inverse correlation with the lipid layer grade (r = -0.343, p = 0.017). Among the participants with thinner tear lipid layers, the complement activation in the tear samples was higher than among those patients with normal tear lipid layers., Conclusion: Seasonal allergic inflammation did not cause permanent tear film instability and eye symptoms were not observed outside the pollen season., (Copyright © 2011 S. Karger AG, Basel.)

Background: Allergic conjunctivitis is characterized by itchy, watery and swollen eyes which occur in response to exposure to seasonal or environmental allergens. The early phase reaction of allergic conjunctivitis is primarily mediated by mast cell degranulation while the late phase reaction is driven by Th2 cells and eosinophils. Prostaglandin D(2) (PGD(2)), released from mast cells, is present in allergic conjunctival tears and may elicit classical allergic responses via interaction with the high-affinity DP2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells, CRTh2). Furthermore, antagonism of this receptor is well known to inhibit eosinophil chemotaxis, basophil activation and Th2 cytokine production. PGD(2), therefore, may be involved in both early and late phase reactions in response to allergen challenge., Methods: Thus, we explored whether our novel and selective DP2 antagonist AM156 would be efficacious in animal models of allergic conjunctivitis. Furthermore, as respiratory syncytial virus (RSV) has been implicated in the pathogenesis of allergic conjunctivitis, we examined the effects of DP2 antagonism in a murine model of RSV ocular infection., Results: Utilizing a guinea pig ovalbumin model and a murine ragweed model we demonstrated that AM156 reduces redness, discharge and swelling in response to allergen challenge. These effects were equal to or greater than those of current clinical treatment options for allergic conjunctivitis including topical corticosteroids and a dual-mechanism antihistamine and decongestant. AM156 significantly reduced RSV-induced ocular inflammation and IL-4 production., Conclusion: These results suggest that a topical DP2 antagonist such as AM156 may represent a novel therapeutic for allergic conjunctivitis., (Copyright © 2011 S. Karger AG, Basel.)

Background: The clinical value of conjunctival allergen challenge (CAC) with latex allergen in patients with allergic conjunctivitis remains undefined. The aim of this study was to assess the value of conjunctival allergen challenge with latex extract in a group of patients with latex sensitization and a history of conjunctivitis after contact with latex products., Methods: Fifty patients who had symptoms of conjunctivitis following contact with latex were studied. The control group consisted of 30 subjects without any symptoms of conjunctivitis, negative skin prick test and sIgE <0.35 kU/l for latex. Questionnaires on signs and symptoms, skin prick tests with latex, sIgE and CAC with latex extract were administered. The study was performed at the Department of Allergology of the Medical University of Gdansk in Poland., Results: CAC with latex was positive in 46 patients (92%) and in none of the control group. CAC was the most sensitive diagnostic method (92% sensitivity and 100% specificity). The sensitivity of other methods (skin prick test and sIgE) was lower: 84 and 88%, respectively. Provocation did not induce any serious adverse events., Conclusion: Our study demonstrated the high sensitivity and safety of CAC with the extract of latex allergens in the diagnosis of patients with latex allergy. This method may be considered a diagnostic option in cases with uncertain diagnosis., (Copyright © 2010 S. Karger AG, Basel.)

Background: Recently, a new commercial test for specific IgE based on immunochromatography (Immfast Check J1®) has been developed. We previously reported on the use of this kit for tear fluid samples during spring. In this study, we compared the level of specific IgE in tear fluid among patients with seasonal allergic conjunctivitis during spring or autumn and control subjects., Methods: A nonrandomized, cross-sectional study was conducted in patients with moderate-to-severe allergic conjunctivitis occurring in spring (n = 56, spring group) or autumn (n = 52, autumn group), as well as in age- and sex-matched healthy control subjects (n = 50, control group). Levels of specific IgE for cedar pollen, cat epithelium and Dermatophagoides pteronyssinus were measured in tear fluid with the Immfast Check J1., Results: Specific IgE scores for cedar pollen and D. pteronyssinus were significantly higher in the spring and autumn groups than in the control group (p < 0.0001). In the autumn group, the highest detection rate for a specific allergen was 96.2% for D. pteronyssinus, followed by cedar pollen (86.5%) and cat epithelium (25.5%). In the spring group, the highest detection rate was 98.3% for cedar pollen, followed by D. pteronyssinus (51.7%) and cat epithelium (19.0%)., Conclusions: These results suggest that both house dust mite allergen and outdoor allergens such as cedar pollen can be causes of allergic conjunctivitis during both spring and autumn in Japan. The Immfast Check J1 provides rapid measurement of specific IgE in tear fluid, which allows easy diagnosis of allergic conjunctivitis in an outpatient setting., (Copyright © 2011 S. Karger AG, Basel.)

Background: Recently, a new commercial test for total tear IgE based on immunochromatography (Allerwatch®) was developed. We examined the relationship between total tear and serum IgE levels with the Allerwatch test., Methods: A nonrandomized cross-sectional study was conducted in 40 patients with allergic conjunctivitis, 35 age- and sex-matched healthy control subjects, and 6 patients with epidemic keratoconjunctivitis (EKC). The total tear IgE score was determined with the Allerwatch test (0, 1 and 2), and the serum total IgE level was measured by solid-phase immunoassay (Phadezym PRIST) in all subjects., Results: Total tear IgE was assayed within 10 min of collection in all samples. The total tear IgE-positive rate was significantly higher in the allergic group than in the control and EKC groups (92.5 vs. 0.0 vs. 0.0%; p < 0.00001). Sensitivity and specificity were 0.925 and 1.000, respectively. The total IgE score and log (total serum IgE) were also higher in the allergic group than in the control and EKC groups [total IgE score: 1.48 ± 0.63 vs. 0.00 ± 0.00 vs. 0.00 ± 0.00, p < 0.00001; log (serum total IgE): 2.23 ± 0.50 vs. 0.80 ± 0.31 vs. 0.79 ± 0.37, p < 0.00001]. The total tear IgE score was significantly correlated with log (total serum IgE) in the allergic group (r = 0.712, p < 0.00001)., Conclusions: These results show that this rapid test for the measurement of total tear IgE is easy to perform on an outpatient basis and may be helpful in the management of ocular allergy., (Copyright © 2010 S. Karger AG, Basel.)

Background: Polymerised allergenic extracts (allergoids) are commonly used in allergen immunotherapy. Clinical efficacy and safety of these extracts have been demonstrated. Recently, allergen sequences have been identified by mass spectrometry in depigmented and polymerised (Dpg-Pol) extracts. The objectives of this study were to investigate the presence of allergens in Dpg-Pol extracts of house dust mite and to analyze the immunological changes induced by these extracts in asthmatic patients enrolled in a double-blind, placebo-controlled study., Methods: Dpg-Pol extracts were manufactured and vaccines with a composition of 50% Dermatophagoides pteronyssinus and 50% D. farinae (100 HEPL/ml) were prepared. Allergen composition was analyzed by mass spectrometry. Patients with asthma and rhinoconjunctivitis were treated in a 1-year, double-blind, placebo-controlled, parallel-group study with 6 up-dosing and monthly maintenance injections. Specific IgE and IgG4 titres to D. pteronyssinus, Der p 1 and Der p 2 were measured in patients' sera using the CAP system and direct ELISA experiments., Results: Sequences from the major allergens Der p 1 and Der p 2 and from other allergens were identified in native and Dpg-Pol extracts. There was a statistically significant increase in specific IgG4, a decrease in the ratio of IgE/IgG4 to D. pteronyssinus and a significant increase in specific IgG4 to Der p 1 and Der p 2 in the patients allotted to active treatment., Conclusions: The detection of allergen sequences suggests preservation of major and minor allergens in Dpg-Pol allergoids from house dust mites. Efficacy in asthma treatment and the increase in specific IgG4 seem to be associated with the presence of major allergens in Dpg-Pol allergen extracts., (Copyright (c) 2010 S. Karger AG, Basel.)

Background: CD11b and F4/80 are macrophage surface markers. How these molecules participate in allergic eosinophil infiltration remains unclear. We examined the roles CD11b and F4/80 play in the conjunctival eosinophil infiltration associated with experimental allergic conjunctivitis., Methods: Ragweed-immunized BALB/c mice were challenged with ragweed in eye drops to induce conjunctival eosinophil infiltration. The effect of challenge on conjunctival CD11b+ and F4/80+ cell numbers was determined by immunohistochemistry. In the same model, blocking anti-CD11b and anti-F4/80 Abs were injected intraperitoneally during the induction or the effector phase, or subconjunctivally 2 h before challenge, to determine their effect on challenge-induced conjunctival eosinophilia. To examine whether eosinophils express CD11b and F4/80 molecules, splenocytes from IL-5 gene-electroporated mice were subjected to flow cytometric analysis. To clarify the involvement of CD11b and F4/80 in conjunctival eosinophil infiltration, mice were intraperitoneally injected with anti-CD11b and anti-F4/80 Abs and then subconjunctivally injected with eotaxin to induce conjunctival eosinophilia., Results: Ragweed challenge elevated conjunctival CD11b+ and F4/80+ cell numbers. Systemic anti-CD11b and anti-F4/80 Ab treatments during the effector phase, but not in either the induction phase or the local injection of Ab, suppressed conjunctival eosinophil infiltration in ragweed-induced conjunctivitis. Most splenic eosinophils from IL-5 gene-introduced mice expressed CD11b and F4/80. Systemic anti-CD11b and anti-F4/80 Ab treatment suppressed conjunctival eosinophilia induced by subconjunctival eotaxin injection., Conclusions: CD11b and F4/80 appear to participate in conjunctival eosinophil infiltration in allergic conjunctivitis. Their involvement in conjunctival eosinophilia appears to be due to their expression on eosinophils rather than on macrophages., (2009 S. Karger AG, Basel.)

Background: Systemic and mucosal roles of eosinophils in the pathogenesis of allergic rhinoconjunctivitis (AR) are known. The aim of this study was to investigate the relationship of clinical parameters and quality of life with eosinophilic cationic protein (ECP) in grass pollen-sensitive children with seasonal AR., Methods: This study included 31 children with AR and 18 healthy controls aged between 5 and 15 years. ECP levels in nasal lavage fluid and serum were measured. AR symptom scores were calculated and the pediatric rhinoconjunctivitis quality of life questionnaire (PRQLQ) was filled in for all patients., Results: Mean serum and nasal ECP levels (ng/ml) were significantly higher in the patient group (p < 0.05 for both). In the AR group, the mean clinical symptom score was 7.3 +/- 2.2, while the total PRQLQ score, activity limitation, symptoms and emotional function domains were 2.5 +/- 0.9, 3.0 +/- 1.1, 2.5 +/- 1.2 and 2.6 +/- 1.1, respectively. The total clinical symptom score and disease duration showed a significant correlation with the total PRQLQ score (p = 0.00 and 0.003, respectively). However, neither nasal lavage nor serum ECP levels were significantly correlated with symptom score, duration of disease, PRQLQ total score or domains (p > 0.05 for all)., Conclusion: These results may indicate the absence of a correlation between clinical status and quality of life and levels of ECP in tissues with allergic inflammation., ((c) 2008 S. Karger AG, Basel.)

Background: We showed previously that treatment with an agonistic anti-4-1BB Ab during the induction phase of murine experimental allergic conjunctivitis (EC) suppresses the development of this model disease. It was reported that 4-1BB promotes the expansion of regulatory T cells. Here we asked whether the suppression of EC by agonistic anti-4-1BB Ab treatment is mediated by regulatory T cells., Methods: Neonatal BALB/c mice were thymectomized and intraperitoneally injected with anti-CD25 Ab. At 6 weeks of age, these mice were immunized with ragweed (RW) in alum. As a control, immunocompetent BALB/c mice were immunized. Ten days later, the mice were challenged with RW in eye drops and 24 h later, the conjunctivas and spleens were harvested for histological and flow-cytometric analyses, respectively. The agonistic anti-4-1BB Ab or control normal rat IgG was injected intraperitoneally during the induction phase of EC., Results: With regard to immunocompetent mice, anti-4-1BB Ab treatment significantly suppressed the severity of EC as evaluated by conjunctival eosinophil numbers. In contrast, in thymectomized and anti-CD25 Ab-treated mice in which CD4+CD25+ regulatory T cells were efficiently depleted, anti-4-1BB Ab treatment did not affect the severity of EC., Conclusions: These results indicate that CD4+CD25+ regulatory T cells play a critical role in the suppression of EC by anti-4-1BB Ab treatment., (Copyright 2008 S. Karger AG, Basel.)

Background: Endogenous IL-17 is needed for the Ag sensitization that results in murine allergic asthma, a Th2-mediated disease. Here, we aimed to investigate the role IL-17 plays in the development of murine experimental allergic conjunctivitis (EC) which is also a Th2-mediated disease., Methods: To induce EC, wild-type (WT) and IL-17-deficient (IL-17 KO) mice on the BALB/c and C57BL/6 backgrounds were immunized with ragweed (RW) in alum and challenged with RW in eye drops. Alternatively, EC was induced by adoptively transferring RW-primed splenocytes followed by challenge with RW-containing eye drops. Twenty-four hours after the RW challenge, the conjunctivas and spleens were harvested for histological analyses and cytokine assays, respectively., Results: The WT and IL-17 KO mice on both backgrounds did not differ in terms of the severity of actively induced EC, as evaluated by the conjunctival eosinophil infiltration. They also did not differ with regard to the phenotypes of the inflammatory cells infiltrating the conjunctivas, although primed IL-17 KO splenocytes stimulated in vitro with RW extract did produce significantly higher amounts of IL-4, IL-13 and IFN-gamma than WT splenocytes. Reciprocal adoptive transfer experiments also demonstrated that the IL-17 from both the donor splenocytes and the recipient mice is not involved in the development of EC., Conclusions: Endogenous IL-17 does not appear to play a significant role in the development of EC., (Copyright (c) 2008 S. Karger AG, Basel.)

Background: Galectin-9 was recently identified as a ligand for Tim-3, which negatively regulates Th1 cells. Here, we investigated whether administration of anti-galectin-9 antibodies (Abs) affects the development of murine experimental allergic conjunctivitis (EC), a Th2-mediated disease., Methods: EC was induced in BALB/c mice by active immunization with ragweed (RW) followed by RW challenge in eye drops. Normal rat IgG (nrIgG) or anti-galectin-9 Ab was injected intraperitoneally into the mice either during the induction phase treatment or effector phase treatment. Alternatively, Abs were injected into the subconjunctival space during the effector phase. To evaluate in vitro effects of anti-galectin-9 Abs, splenocytes from RW-sensitized mice were cultured in vitro with RW in the presence of nrIgG or anti-galectin-9 Abs. To induce EC, these splenocytes were transferred into naïve BALB/c mice followed by RW challenge., Results: Treatment with anti-galectin-9 Abs in vivo during either the induction or effector phase did not significantly affect the severity of EC. However, when the splenocytes from RW-primed mice treated with anti-galectin-9 Abs during the induction phase were stimulated in vitro and adoptively transferred into naïve recipients, they induced significantly severer EC. In contrast, when RW-primed splenocytes were restimulated in vitro with RW in the presence of anti-galectin-9 Abs and then adoptively transferred, they induced less severe EC and produced significantly less IL-5 and IL-13 and more IFN-gamma compared to nrIgG-treated control splenocytes., Conclusions: These observations may reflect the fact that galectin-9 not only regulates T-cell function, it is also involved in many other biological functions., (Copyright 2007 S. Karger AG, Basel.)

CD4+ CD25+ T cells regulate various kinds of immune-mediated diseases. Here, we sought to clarify whether CD4+ CD25+ T cells also regulate the development of experimental allergic conjunctivitis (EC). Thymectomized BALB/c mice, treated with anti-CD25 antibody (PC61), normal rat immunoglobulin G (nrIgG) or left untreated were immunized with short ragweed pollen (RW). Ten days later, the mice were challenged with RW in eye drops, and 24 h later, the conjunctivas, blood and spleens were harvested. The severity of EC, as evaluated by conjunctival eosinophil numbers, was significantly higher in the PC61-treated group as compared with the other two groups. The PC61-treated group also had significantly higher RW-specific IgE and IgG1 levels and displayed RW-specific splenocyte proliferation and RW-induced splenocyte T helper cell 2 cytokine production. However, PC61 treatment of unthymectomized mice did not affect the severity of EC. Thus, thymus-derived CD25+ T cells regulate the development of EC. Furthermore, transfer of Foxp3-expressing CD4+ CD25+ T cells from naïve mice into RW-sensitized mice suppressed the development of EC in these mice after RW challenge. Taken together, these results suggest that CD4+ CD25+ T cells regulate the development of EC., (Copyright 2007 S. Karger AG, Basel.)

Background: The efficacy of standardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens., Methods: Forty adults with European cypress-allergic rhinoconjunctivitis were randomized to receive immunotherapy or a matched placebo. Specific immunotherapy was performed with a standardized, aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR (arbitrary index of reactivity) containing 54 microg of Jun a 1/ml (Alustal, Stallergenes, France). Subcutaneous injections started in October 2000. The maintenance dose was 0.30 ml of the 100-IR concentration per month. Rhinitis and conjunctivitis symptoms were rated according to a 4-point score., Results: Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001; 14 in each group completed year 2002. A statistically significant improvement (41%, p < 0.02) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season. Improvement in rhinitis (17%) was not significant. This significant improvement was greater at the peak of the 2002 pollen season (63%, p < 0.01)., Conclusions: This study therefore indirectly validates the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted.

Interleukin (IL)-10 is known to act as an immunoregulatory cytokine in both T helper cell 1 (Th1)- and Th2-mediated immune responses. Here, we ask whether IL-10 regulates the development of experimental allergic conjunctivitis (EC), a Th2-mediated inflammatory disease. Wild-type (WT) and IL-10 knockout (IL-10 KO) mice were immunized with ragweed (RW) and then repeatedly challenged with RW in eye drops. Twenty-four hours after the final challenge, conjunctivas were harvested for histological analysis, while the blood and spleens were used to determine the RW-specific immunoglobulin levels in serum and proliferation or cytokine responses and splenocyte transfer, respectively. The IL-10 KO mice had significantly less severe EC (as determined by conjunctival eosinophil infiltration) than the WT mice and evinced greater RW-specific splenocyte proliferation and cytokine production. However, the RW-specific immunoglobulin levels of the two strains did not differ. When the splenocytes from RW-primed WT mice were transferred into IL-10 KO or WT mice, the IL-10 KO mice showed significantly less conjunctival eosinophil infiltration. In contrast, when the splenocytes from RW-primed IL-10 KO or WT mice were transferred into WT mice, both splenocyte populations generated equivalent severe EC. These data indicate that IL-10 does not serve as an immunoregulatory cytokine in the development of EC. Instead, it appears that IL-10 produced by antigen-irrelevant cells acts in the effector phase to promote the development of EC.

Background: Recent work indicates that subcutaneous specific immunotherapy induces specific T-cell anergy, a shift in the TH1/TH2 ratio, and antibody production in favor of IgG4. There are few data on sublingual immunotherapy (SLIT), especially in children., Methods: We assessed the proliferation of peripheral blood mononuclear cells ((3)H-thymidine incorporation) and secretion of interleukin (IL)-4, interferon (IFN)gamma and IL-5 (ELISA) after in vitro stimulation with allergen or phytohemagglutinin (PHA) in 29 children with allergic rhinoconjunctivitis receiving SLIT with grass pollen before, and after 1 and 2 years of treatment in a multicenter placebo-controlled study on the efficacy of the treatment. Further, non-specific intracellular production of IL-4, IL-13, IFNgamma, IL-2, IL-10 and IL-5 (FACS) and serum total and specific IgE and IgG4 (ELISA) were analyzed., Results: Proliferation and IL-4 and IL-5 secretion after stimulation with allergen or PHA did not differ between the groups. In addition, we observed no effect of SLIT on intracellular cytokine production. IFNgamma secretion after allergen coculture was comparable between the groups. Following PHA stimulation, IFNgamma secretion was significantly higher in the SLIT group after 1 year, and a trend was observable already before and after 2 years of treatment, probably due to the inhomogeneity in the groups despite randomization (for age and asthma). No significant changes were observed for sIgE/sIgG4 ratios over time either in or between the groups., Conclusion: During 2 years of SLIT in children with a positive effect on rescue medication use, we observed no significant effects on in vitro T-cell immune responses or immunoglobulins. So far, pediatric studies demonstrating stable effects of SLIT on such reactions are missing, probably due to limited effects of SLIT on systemic immunologic reactions., (Copyright (c) 2005 S. Karger AG, Basel.)

Background: Allergen immunotherapy is a widely accepted treatment for IgE-mediated allergies. The evaluation of immunotherapy-induced IgG4 antibodies based on allergen extract is questionable because the amount of allergen-extract-specific IgG4 to individual disease-eliciting allergens cannot be determined using crude allergen extracts. In this study, we examined the specific IgE and IgG4 serum binding profiles to individual Phleum pratense allergens in grass-pollen-sensitive patients who had received grass-pollen-specific immunotherapy (SIT)., Methods: The study included 33 patients from North-West Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. A modified "cluster" regimen of injections of a standardized aluminium-adsorbed P.pratense extract, with once-weekly visits and 10 injections for 5 weeks followed by 3 weeks of maintenance injections was instituted. Patients' sera were analyzed for specific IgE and IgG4 reactivity to individual P. pratense allergens (recombinant Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 7, Phl p 11, Phl p12 and native Phl p 4) and natural P. pratense extract using the Pharmacia CAP system., Results: IgE reactivities to new allergen components were not detected by CAP in treated patients after 15 weeks and a cumulative dose of approximately 65 microg of the major allergen Phl p 5. Patients lacking specific IgE reactivity towards individual allergens at the start of SIT did not produce significant levels of specific serum IgG4 to serum IgE-negative allergens. On the other hand, an increase in specific IgG4 only to allergens to which patients were previously sensitized was observed. Significant increases in specific IgG4 levels to rPhl p 1 (p < 0.05), 2 (p < (0.01), 5 (p < 0.0001), 6 (p < 0.0001), 7 (p < 0.05), 11 (p < 0.05) and nPhl p 4 (p < 0.01) were observed after P. pratense extract immunotherapy. No significant rPhl p 12-specific IgG4 antibody increase was documented after treatment., Conclusion: These findings suggest that Phl p 12 was underrepresented in the extract used, as indicated by the low specific IgG4 response induced by this grass-pollen-specific vaccine. Thus, the simple detection of specific serum IgG4 antibodies a few weeks after the start of SIT could represent a valuable tool to estimate the presence of relevant allergens in a given immunotherapeutic allergen extract., (Copyright 2004 S. Karger AG, Basel)

Background: Workers in hydroelectric plants appear to be readily sensitized to caddisfly allergens. This sensitization probably occurs de novo from occupational exposure. In some workers, sensitization occurs on a non-atopic background. Cytokine synthesis of IFN-gamma, IL-5 and IL-13 in atopic and non-atopic caddisfly-allergic workers was examined to determine if responses were similar or different., Methods: Peripheral blood mononuclear cells were isolated from atopic caddisfly-allergic workers, non-atopic caddisfly-allergic workers and non-atopic caddisfly-exposed but non-allergic workers. Stimulation with caddisfly antigens was carried out and synthesis of IFN-gamma, IL-5 and IL-13 was determined by sandwich ELISA., Results: Both caddisfly-allergic and non-allergic subjects responded to stimulation with caddisfly extract. The response in non-atopic caddisfly-non-allergic subjects was TH1 predominant, while that in atopic caddisfly-allergic subjects was TH2 predominant. The response in non-atopic caddisfly-allergic subjects was between that of the atopic caddisfly-allergic workers and the non-atopic caddisfly-non-allergic workers and the trend was to a TH2 response. Work-related symptoms were similarly intermediate between the atopic caddisfly-allergic and non-atopic caddisfly-non-allergic group. Differences were significant for IFN-gamma/IL-5 ratios but not IFN-gamma/IL-13 ratios for atopic and non-atopic caddisfly-allergic individuals, compared to non-atopic caddisfly-non-allergic workers. However, a linear relationship existed between IFN-gamma synthesis and IL-5 and IL-13 synthesis in non-atopic caddisfly-allergic workers but not in atopic caddisfly-allergic subjects., Conclusions: Caddisfly allergy in hydroelectric workers may be a useful model for the development of allergy to a previously unencountered allergen, and points to some interesting differences between atopic and non-atopic subjects who become sensitized to environmental allergens., (Copyright 2003 S. Karger AG, Basel)

Background: Blomia tropicalis and Dermatophagoides pteronyssinus are important mite species in Tenerife, Canary Islands, Spain. Several studies have demonstrated a variable degree of allergenic cross-reactivity in vitro. However, only a few have addressed their allergenic cross-reactivity using challenge tests., Objective: The objective of this study was to conduct conjunctival and bronchial challenge tests with B. tropicalis and D. pteronyssinus extracts in a group of 42 patients with allergic asthma and/or rhinoconjunctivitis sensitised to house dust mites (31 females, 11 males; mean age 21.7 +/- 7.02 years)., Methods: Prick tests using standardised extracts and specific IgE determinations using the CAP system were performed. Bronchial and/or conjunctival challenges were conducted using freeze-dried extracts of both mite species. A patient was considered sensitive to a mite species if she/he had a positive prick and/or CAP test result. A total of 32 conjunctival and 15 bronchial challenges were performed with both mite species., Results: Prick tests were positive to B. tropicalis in 23 patients (54.7%) and to D. pteronyssinus in 41 (97.6%). One patient (2.4%) was exclusively sensitive to B. tropicalis. The CAP test was positive for B. tropicalis in 28 patients and for D. pteronyssinus in 41. Conjunctival challenges to B. tropicalis were positive in 20 patients (18 sensitised and 2 non-sensitised) and negative in 12 (5 sensitised and 7 non-sensitised patients). Conjunctival challenges with D. pteronyssinus were positive in all 31 D. pteronyssinus-sensitised patients who underwent conjunctival challenges. Bronchial challenges with B. tropicalis were positive in 9 sensitised patients and negative in 6 patients (2 sensitised and 4 non-sensitised). Bronchial challenges with D. pteronyssinus were positive in all patients except 1, who only reacted to B. tropicalis., Conclusions: Allergens of the mite species B. tropicalis induce positive conjunctival and bronchial challenges in B. tropicalis-sensitised individuals. Our results suggest that although there is a low to moderate degree of in vivo cross-reactivity between B. tropicalis and D. pteronyssinus, B. tropicalis seems to be a relevant source of allergens in areas where patients are exposed., (Copyright 2003 S. Karger AG, Basel)

Background: Sensitivity to birch pollen allergens is a common feature among European patients with seasonal pollen allergy. In this in vitro study, we examined the specific serum IgE binding profiles to individual birch pollen allergens in birch-sensitive patients from six European populations., Methods: The study included 242 patients from Finland, Sweden, Austria, France, Switzerland and Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. Their sera were analyzed for specific IgE reactivity to individual birch pollen allergens (recombinant Bet v 1, Bet v 2 and Bet v 4) and natural birch pollen extract using Pharmacia CAP System and immunoblotting., Results: Almost all Finnish, Swedish and Austrian sera contained IgE specific for Bet v 1 (>or=98%). Bet v 1-specific IgE antibodies were found in 90% of the French sera, and in 65 and 62% of the sera from Switzerland and Italy, respectively. Few Finnish (2%) and Swedish (12%) patients had IgE to Bet v 2, while Bet v 2 reactivity was more common in the other populations (20-43%). Reactivity to Bet v 4 was rare in all populations (5-11%) except for the Italian patients, in whom 3 of 11 sera were positive (27%). The immunoblot results supported the specific IgE profiles obtained with Pharmacia CAP System showing a broader IgE reactivity profile in patients from central and southern Europe as compared to northern Europe., Conclusion: Component-resolved allergy diagnosis with recombinant allergens reveals that the IgE reactivity profiles to individual birch pollen allergens vary between European populations. This observation may be explained by sensitization to different allergen sources and will have an impact on allergen-specific prevention and therapy strategies., (Copyright 2002 S. Karger AG, Basel)

Background: Japanese cedar pollinosis is an important allergic rhinoconjunctivitis in Japan in spring. We investigated the relationship between the amount of pollen in the air and the prevalence of the disease and sensitization to Japanese cedar pollen in this ecological study., Methods: The IgE antibody to Japanese cedar pollen (JCP-IgE) was determined in human serum and rhinoconjunctival symptoms were surveyed in 407-510 children in May or June every year from 1995 to 2001. Japanese cedar pollinosis was defined as being JCP-IgE >or=1.5 IU/ml and having any rhinoconjunctival symptom lasting 3 weeks or longer in March or April., Results: Prevalence rates of Japanese cedar pollinosis were 13.8-22.9%. Prevalence rates of being JCP-IgE >or=1.5 IU/ml were 39.0-50.1%, and those of being JCP-IgE >or=15.01 IU/ml were 11.4-23.2%. All prevalence rates were significantly related to the amount of pollen in the air. The proportion of subjects with rhinoconjunctival symptoms was relatively constant in each stratum of low JCP-IgE levels (<0.35, 1.50-2.99, 3.0-14.9 IU/ml)., Conclusion: High exposure to Japanese cedar pollen was associated with higher levels of JCP-IgE antibody and a high prevalence of Japanese cedar pollinosis. The relationship between the level of JCP-IgE and the proportion of subjects with symptoms was relatively constant., (Copyright 2002 S. Karger AG, Basel)

Red soft coral (RSC; Dendronephthya nipponica, a marine coelenterate) causes spiny lobster fishermen living along the Pacific coast of Miyazaki Prefecture in Japan to develop occupational allergies, such as conjunctivitis, rhinitis, dermatitis and bronchial asthma. The aim of this study was to purify and to characterize RSC allergen, which causes occupational asthma in spiny lobster fishermen. The allergic responsiveness of spiny lobster fishermen to RSC was examined. The examinations included specific IgE production, skin test responses, lymphocyte stimulation tests and specific IgG production. We found that RSC has a strong sensitizing activity in humans at a molecular weight of 10 kD or more, while it has no IgE-producing activity at a molecular weight of less than 10 kD. Neither the nonatopic controls nor the atopic non-coral-allergic controls exhibited any RAST-binding activity to any fraction. For the purification and the identification of this new allergen component, repeated gel filtration of the RSC extract was performed on a Sephacryl S-200 column, followed by gel filtration on a Superose-6 column. The purified major allergen component Den n 1, which is separated on a Mono-Q column, showed intradermal responses, lymphocyte stimulating activity and specific IgG-producing activity in RSC-induced bronchial asthma patients. The 53-kD component was electroblotted on a polyvinylidene difluoride membrane. The N-terminal amino acid sequence of this new allergen component (Den n 1) was determined as Asp-Asp-Ile-Asn-Arg-Tyr-Ala-Phe-Asp-Asn-Lys-Ile-Asn- Asp-Lys-Leu-Phe-Asp-His-Trp-Gln-Ser., (Copyright 2001 S. Karger AG, Basel)

Background: We have previously shown aberrant expression of the 'leukocyte' integrin LFA-1 on epithelial cells in chronic autoimmune thyroiditis. In the present study we investigated whether conjunctival epithelial cells, which bear the adhesion molecule ICAM-1 on their surface during allergic inflammation, may also aberrantly express its natural ligand, the 'leukocyte' integrin LFA-1., Methods: We studied 13 patients with rhinoconjunctivitis allergic to mites, chronically exposed to the allergen, 11 patients allergic to pollen tested out of the pollen season and 8 normal volunteers. Single and double immunocytochemical staining of conjunctival smears was employed., Results: LFA-1 staining on epithelial cells was demonstrated in 12/13 patients allergic to mites and not in normal controls or in patients allergic to pollen tested out of the pollen season. The epithelial localization of LFA-1 was confirmed by double staining with anti-LFA-1 and anti-cytokeratin antibodies (both immunocytochemical and immunofluorescence)., Conclusions: Coexpression of LFA-1 and ICAM-1 during persistent allergen stimulation may be relevant for interaction between epithelial cells and activated effector cells, such as eosinophils, which bear on their surface both ICAM-1 and its beta2 integrin ligands., (Copyright 2001 S. Karger AG, Basel)

A number of structurally different allergens trigger the release of mediators from basophils by cross-linking of IgE receptors. In this study, we analyzed the effects of cyclosporine A (CSA) and FK-506 on allergen-induced histamine release in human blood basophils obtained from birch- or grass-pollen-allergic donors (n = 12). Preincubation of basophils with CSA (0.003-3 microg/ml) or FK-506 (0.003-3 microg/ml) led to inhibition of histamine release induced by purified recombinant tree pollen allergens (r Bet v 1, r Bet v 2) and timothy grass pollen allergens (r Ph1 p 1, r Ph1 p 2, r Ph1 p 5). The effects of CSA and FK-506 were dose dependent, with IC50 values ranging between 0.03 and 0.3 microg/ml for both CSA and FK-506. Cyclosporine H, an inactive CSA analog, did not show any effect on allergen-induced histamine secretion. IgE dependency of the reaction was demonstrated in passive transfer experiments using highly enriched human basophils (> 95% pure) and specific IgE from a patient allergic to Bet v 2. In summary, our data show that CSA and FK-506 inhibit recombinant-allergen-induced histamine release from peripheral blood basophils in allergic donors.

A previous study has reported a strong association of a variant (Ile181Leu) of the beta-subunit of the high-affinity IgE receptor (Fc epsilon RI-beta) with allergic asthma bronchiale in a random patient sample. Based on their results the authors concluded that Fc epsilon RI-beta may be the maternally inherited, atopy-causing locus. We have investigated 40 unrelated atopic patients, 30 with allergic asthma and 10 with atopic dermatitis or allergic rhinoconjunctivitis along with some of their relatives for the presence of Ile181Leu by nucleic acid sequence analysis and/or hybridization with mutation-specific oligonucleotide probes. None of the probands showed this mutation suggesting that its association with atopy may be restricted to certain populations or occur at lower frequency than reported.

Allergy to pollen of Cupressaceae has been linked to pollens of Cupressus, Juniper and Cryptomeria. The authors report 2 cases of rhinitis and conjunctivitis induced by thuja, another member of the Cupressaceae family. Monosensitization to thuja pollen has been identified as the causal agent: (1) of a long-standing springtime rhinitis in 1 patient with negative skin tests and specific IgE titers to the main inhalants (specificity of the prick test and nasal provocation with the thuja extract was confirmed by a positive RAST) and (2) in a 2nd patient without former history of allergy, who consulted for conjunctivitis following acquisition of a dog; the standard battery of skin tests, and Phadiotop were all negative. After controls, only the thuja extract gave significant skin test response. The level of total IgE was low, and RAST was negative. Sensitization and pollen provocation were produced by the intermediary of the dog, carrying thuja pollens on its fur. The immunoprint and the crossed radioimmunoelectrophoresis revealed common antigenicity between cypress and thuja extracts.

Clinical studies of vernal keratoconjunctivitis (VKC) patients show that total IgE serum levels are increased even in the absence of IgE antibodies to common allergens. Activated eosinophils are also a constant feature of VKC at both the circulation (cytofluorimetry) and tissue (tear cytology and conjunctival scrapings) levels. Moreover, allergen challenge induces a prolonged inflammatory reaction with a prevalent participation of eosinophils, lymphocytes and possibly basophils. Immunohistochemical studies of VKC biopsies show a multicellular inflammatory infiltrate with prevalence of activated eosinophils, mast cells and CD4 lymphocytes in both epithelium and subepithelium. Mediator studies indicate that eosinophil products (eosinophil peroxidase, eosinophinal cationic protein and eosinophil-derived neurotoxin/eosinophil protein X) are increased in both serum and tears, where tryptase and interleukin (IL)-5 are also detectable in higher amounts than in controls. On the basis of these findings, we postulate that VKC can represent a phenotypic model of up-regulation of the cytokine gene cluster on chromosome 5q which through its products (IL-3, IL-4, IL-5 and granulocyte/macrophage-colony-stimulating factor) regulates Th2 prevalence, IgE production as well as mast cell and eosinophil growth and function in VKC.

Nonspecific hyperreactivity to a number of physical, chemical and pharmacological agents in a common characteristics of allergic subjects, which is strictly related to the inflammatory events consequent to an allergic reaction. Hyperosmolar stimulus has previously been shown to cause an inflammatory response inducing mast cell activation and subsequent mediator release. We investigated the clinical and cytological events following conjunctival challenge using a hyperosmolar agent (i.e. glucose solution) in patients with allergy due to pollen, in patients with allergy due to mites and in healthy individuals in order to investigate the possible existence of 'conjunctival hyperreactivity', similar to the well-known nasal and bronchial nonspecific hyperreactivity in allergic patients. Hyperosmolar stimulus was able to produce an immediate inflammatory response evidenced by clinical symptomatology, inflammatory cell infiltrate and CD54 expression on conjunctival epithelium in all allergic subjects and healthy volunteers. House dust mite-sensitive subjects, but not pollen-sensitive subjects studied out of pollen season, showed conjunctival hyperreactivity as shown by histamine challenge, in that they required lower glucose concentrations to elicit the conjunctival reaction. This is probably related to an underlying although mild, inflammation.