Japanese Cedar Pollen-specific IgE Research Articles

Safety profile and immunological response of dual sublingual immunotherapy with house dust mite tablet and Japanese cedar pollen tablet

BackgroundThere have been no studies of dual administration of sublingual immunotherapy (SLIT) tablets for perennial and seasonal allergic rhinitis. This trial (JapicCTI-184014) was conducted to investigate the safety profile and immunological response during dual therapy with SQ house dust mite (HDM) and Japanese cedar pollen (JCP) SLIT tablets. MethodsThis was a multicenter, open-label, randomized trial of 109 Japanese patients with coexisting HDM and JCP allergic rhinitis who had positive tests for HDM- and JCP specific IgE (≥0.7 kU/L). Patients were allocated to receive HDM (N = 54) or JCP (N = 55) SLIT tablets alone for 4 weeks followed by 8 weeks of dual therapy with both SLIT tablets administered within 5 min of each other. Adverse events (AEs), adverse drug reactions (ADRs), and serum IgE and IgG4 specific for HDM (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and JCP were recorded. ResultsThe percentage of subjects with AEs and ADRs was similar between the two groups and between the two periods of monotherapy and dual therapy. Most AEs and ADRs were mild in severity, and no serious events were observed. The most common ADRs were local events in the oral cavity. Levels of IgE and IgG4 specific for HDM (D. farinae, D. pteronyssinus) and JCP were increased after treatment with HDM and JCP SLIT tablets, respectively. ConclusionsDual therapy with both SLIT tablets administered within 5 min after 4 weeks of monotherapy with HDM or JCP tablet was well tolerated and induced the expected immunological responses.

Peripheral basophil reactivity, CD203c expression by Cryj1 stimulation, is useful for diagnosing seasonal allergic rhinitis by Japanese cedar pollen.

Measuring specific IgE can yield direct, accurate, and objective data. Nevertheless, clinical symptoms of allergy are often inconsistent with these data. Recently, the expression of CD203c, a surface marker of basophils, has been reported as capable of distinguishing allergic patients. This study compared specific IgE in serum and skin tests against antigen to assess CD203c as a biomarker correlated with allergic rhinitis (AR). We asked 3,453 subjects whether they experienced any AR related symptom. All subjects were assessed for six specific IgEs for common aeroallergens. Skin tests were also conducted for six aeroallergens. We observed the reactivity of peripheral basophil by measuring the levels of CD203c by Cryj1 stimulation using flow cytometry. Of the 3,453 participants, 1,987 (57.5%) possessed Japanese cedar pollen (JCP) specific IgE in their serum. Among those 1,987 JCP specific IgE positive participants, 552 (27.8%) had not experienced any allergic symptom during the JCP season. The levels of CD203c in the peripheral basophil by Cryj1 stimulation were significantly higher in SAR-JCP subjects than in non-SAR-JCP subjects (Cryj1 0.5 ng/ml: 2.25 ± 0.90% vs. 60.2 ± 27.4%, p < 0.01, Cryj1 50 ng/ml: 1.89 ± 0.90% vs. 68.0 ± 21.2%, p < 0.01). Our results indicate that the levels of CD203c in peripheral basophils by Cryj1 stimulation is a more objective and reliable marker that better reflects the allergic reaction by SAR-JCP in vivo than measuring specific IgE in serum or skin tests.

Changes of micro-RNAs in asymptomatic subjects sensitized to Japanese cedar pollen after prophylactic sublingual immunotherapy.

Japanese cedar pollinosis is the predominant seasonal allergic rhinitis in Japan, and it has increased in prevalence during the past 10 years. Sublingual immunotherapy (SLIT) is considered a safe and effective treatment for pollinosis. Micro-RNAs (miRNAs) are a class of short single-stranded RNA molecules that posttranscriptionally silence gene expression and may mediate allergic immune responses. The aim of this study was to investigate the miRNA alteration in asymptomatic subjects sensitized to Japanese cedar pollen under prophylactic SLIT under part of a randomized, double-blind, placebo-controlled, multiple-center trial. Analysis was undertaken in 15 asymptomatic subjects sensitized to Japanese cedar pollen–specific IgE (ImmunoCAP class ≥2) who participated in 2013. The SLIT group (n = 6) received standardized Japanese cedar pollen extract and the placebo group (n = 9) received an inactive placebo for 5 months covering the cedar pollen season. Changes in serum miRNAs were measured by real-time quantitative polymerase chain reaction to determine whether SLIT had effects on profiles of circulating miRNA. Seven subjects in the placebo group developed pollinosis symptoms, whereas no subjects in the SLIT group did (p = 0.007). Serum hsa-miR-223 was significantly up-regulated in postseason compared with preseason samples. The hsa-let-7b was significantly more down-regulated in postseason than in preseason samples from the placebo group; however, no significant differences were observed in those from the SLIT group. A significant decrease in circulating let-7b was also observed in the subjects who developed symptoms. Prophylactic SLIT was effective in preventing the development of pollinosis. Alterations in miRNA expression occurred in asymptomatic, sensitized subjects during cedar pollen season.

Immunological parameters in prophylactic sublingual immunotherapy in asymptomatic subjects sensitized to Japanese cedar pollen

BackgroundThis study aims to examine the immunological parameters, focusing IL-10 productivity, in prophylactic sublingual immunotherapy (SLIT) in asymptomatic subjects sensitized to Japanese cedar pollen (JCP). MethodsThis study was conducted as part of a randomized, double-blind, placebo-controlled, multiple center trial, and was performed for two consecutive pollen seasons in 2012 and 2013. The present results were based only on our institution. We recruited 29 participants with specific IgE against JCP of at class 2 and higher levels without history of the pollinosis symptoms at the time of JCP scattering. The SLIT group received standardized JCP extract for five months over the pollen season. We observed and judged development of the symptoms in the pollen season. The percentage of IL-10 producing CD4+ T (Trl) cells, B cells and monocytes were analyzed by flow cytometry. JCP specific IgE and total IgE were also measured. ResultsThe ratio of development of cedar pollinosis was significantly lower in the SLIT group compared to the placebo group in 2013. In 2012, the percentage of circulating Tr1 cells and IL-10 producing monocytes significantly increased in the SLIT group. In 2013, the percentage of circulating Tr1 cells and IL-10 producing B cells increased significantly in the SLIT group. The percentage of circulating IL-10 producing monocytes significantly decreased in the placebo group. ConclusionsProphylactic SLIT is effective for prevention of the development of pollinosis. Induction of IL-10 producing T cells, B cells and monocytes is an important mechanism of SLIT for prevention of pollinosis in asymptomatic but sensitized subjects.

Measurement of Japanese Cedar Pollen-Specific IgE in Nasal Secretions

Japanese cedar pollen (JCP) is the most common allergen for seasonal allergic rhinitis in Japan. Little is known about local production of immunoglobulin (Ig)E in people with or without Japanese cedar pollinosis. The aims of this study were to measure levels of JCP-specific IgE in nasal secretions and determine correlations with levels in serum. Forty-six subjects were enrolled in this study, comprising 24 symptomatic subjects, 9 asymptomatic subjects sensitized to JCP, and 13 subjects not sensitized to JCP. Nasal secretions were obtained during a period of Japanese cedar dispersal, and levels of JCP-specific IgE were measured with CAP-fluorescent enzyme immunoassay. Serum JCP-specific IgE and total IgE were also measured using the same method. Among the 46 subjects enrolled, JCP-specific IgE in nasal secretions was measureable in 43 subjects. Irrespective of symptom development, sensitized subjects showed higher levels of JCP-specific IgE in nasal secretions than non-sensitized subjects. A significant moderate correlation was observed between JCP-specific IgE levels in nasal secretions and serum in all 43 subjects. With stratification by subject group, only symptomatic subjects showed a substantial correlation between JCP-specific IgE levels in nasal secretions and serum. Our results imply a certain association between JCP-specific IgE in nasal secretions and sensitization of Japanese cedar pollinosis. Therefore, levels of allergen-specific IgE in nasal secretions can be used as an alternative diagnostic marker for allergic rhinitis patients.

Efficacy ofLactobacillus plantarumStrain HSK201 in Relief from Japanese Cedar Pollinosis

To determine the effects of Lactobacillus plantarum strain HSK201 on Japanese cedar pollinosis, a single-blind, placebo-controlled study was conducted in 2008. The HSK201 group was administered fermented milk prepared with HSK201 for 8 weeks, and the placebo group was administered non-fermented milk adjusted to the same acidity and taste. We found HSK201 strain intake to suppress both helper T cell type 1/2 ratio reduction and serum Japanese cedar pollen-specific IgE elevation at the peak of pollen dispersion. In addition, the nasal and ocular symptom scores in the HSK201 group were also lower than those in the placebo group during the early phase of the pollen season. Although this was a preliminary study with 19 employees of our own company serving as subjects, the results suggest that ingestion of the HSK201 strain alleviates pollinosis symptoms during the period when pollen exposure is low and the symptoms are mild.

Efficacy of Oral Administration of a Heat-KilledLactobacillus gasseriOLL2809 on Patients of Japanese Cedar Pollinosis with High Japanese-Cedar Pollen-Specific IgE

A randomized, double-blind, placebo-controlled clinical trial was conducted to determine whether oral administration of heat-killed Lactobacillus gasseri OLL2809 would affect the immune response and reduce the symptoms of Japanese cedar pollinosis (JCP) in subjects with JCP. Following a 1-week pre-observation period, the subjects were randomly divided into two groups and were orally administered a placebo or tablets containing 100 mg of L. gasseri OLL2809 per d for 8 weeks during the pollen season in 2007. The results showed no obvious differences between the groups. Supplementary subgroup analysis revealed that the OLL2809 subgroups with CAP-RAST scores of 4 or 5 exhibited improvement in nasal symptoms scores and serum allergy-related items, including Japanese cedar pollen-specific IgE levels. L. gasseri OLL2809 was found to be effective in reducing symptoms in subjects with a high predisposition to allergies by modulating systemic immune systems.

Clinical Evaluation of Measurement Method for Antigen Specific IgE in Tears of Patients with Allergic Conjunctival Disease

To investigate a method for determining antigen specific IgE antibodies in tears of patients with allergic keratoconjunctival disease. Antigen specific IgE antibodies to Japanese cedar pollen or Housedust-Mites in tears of patients with allergic conjunctival diseases were examined. Both eyes in each patient were examined. The right eye was examined in normal healthy volunteers as a control. The number of eyes examined for IgE antibodies to Japanese ceder pollen was 32 eyes with seasonal allergic conjunctivitis(SAC), 12 eyes with perennial allergic conjunctivitis(PAC), 12 eyes with atopic keratoconjunctivitis (AKC), 4 eyes with vernal keratoconjunctivitis (VKC), and 12 eyes of the controls. The number of eyes examined for IgE antibodies to Housedust-Mites was 32 eyes with SAC, 20 eyes with PAC, 30 eyes with AKC, 22 eyes with VKC, and 10 eyes with the control. Tears were sampled by the method of Schirmer Test-1. Sampled tears were eluded with 200 microliters of phosphate buffered solution(pH 7.2, 0.05 M) and analyzed by the AlaSTAT-IMMULYZE method. Recovery rate of absorbance by filter paper for IgE antibodies in tears was determined by ratio to the standard sample of serum solution containing Housedust-Mite specific IgE antibodies with known concentration. Recovery rate of filter paper for IgE antibodies in tears was 83.6%. IgE antibodies in tears to Japanese cedar pollen were detected in 11 of 32 eyes of SAC. In other subjects, IgE antibodies were under the limit of the detection concentration except one eye of a patient with AKC. In the positive cases of Japanese cedar pollen specific IgE antibodies, there was no significant difference in the concentration between the right and the left eyes. IgE antibodies to Housedust-Mites were significantly higher not only in incidence but also in concentration in 18 of 22 eyes with VKC than in that in other in 8 of 20 eyes with PAC and 12 of 30 eyes with AKC. The method for determining antigen specific IgE antibodies in tears is clinically useful to diagnose and to investigate pathophysiology of allergic conjunctival diseases.

Reduction of Allergic Skin Responses and Serum Allergen-Specific IgE and IgE-Inducing Cytokines by Drinking Deep-Sea Water in Patients with Allergic Rhinitis

Deep-sea water intake reduces allergic skin responses and serum levels of total IgE, Japanese cedar pollen-specific IgE, interleukin (IL)-4, IL-6, IL-13, and IL-18 in patients with allergic rhinitis, while distilled water intake fails to do so.

Clinical Evaluation of Lumiward Immunoassay System for Detection of Specific IgE Associated with Allergic Rhinitis

The detection of specific IgE is a critical prerequisite for both the definitive diagnosis and the therapeutic strategy of allergic rhinitis and other allergic disorders. The aim of the present study was thus to evaluate the clinical significance of the solid phase capture system (CAP) and the lumiward immunoassay system (LMD) in the diagnosis of allergic rhinitis due to Dermatophagoides farinae ( D. farinae ) and Japanese cedar ( Cryptomeria japonica ) pollens. The specificity of both the CAP and the LMD in the detection of D. farinae -specific IgE and Japanese cedar pollen-specific IgE was 100%. The sensitivity to detect D. farinae -specific IgE was 95.76% in the skin test, 86.53% in the CAP and 88.53% in the LMD, respectively. The combination of the nasal provocation test and the CAP substituted for the skin test resulted in correct diagnoses for 98.25% of the patients, and the combination of the nasal provocation test and the LMD substituted for the skin test resulted in correct diagnoses for 98.00% of the patients. Therefore, the diagnostic significance of the LMD for perennial allergic rhinitis is likely to be equal to that of the CAP. The sensitivity to detect Japanese cedar pollen-specific IgE was 94.50% in the skin test, 84.47% in the CAP, and 96.76% in the LMD, respectively. The sensitivity of the CAP in the detection of Japanese cedar pollen-specific IgE was inferior to that of the skin test, but the sensitivity of the LMD in the detection of pollen-specific IgE was somewhat superior to that of the skin test. In addition, the combination of the nasal provocation test and the CAP substituted for the skin test resulted in correct diagnoses for 98.38% of the patients, whereas the combination of the nasal provocation test and the LMD substituted for the skin test resulted in correct diagnoses for 100% of the patients. Therefore, the diagnostic significance of the LMD for seasonal allergic rhinitis due to Japanese cedar pollens is probably larger than that of the CAP. In conclusion, the LMD may be a better “gold standard” for the detection of Japanese cedar pollen-specific IgE than the skin test, and the combination of the nasal provocation test and the LMD is a better diagnostic tool for the detection of Japanese cedar pollen-induced seasonal allergic rhinitis than the combination of the nasal provocation test and the skin test or the CAP.

Cry j 1-induced Synthesis of Interleukin-5 and Interferon-Gamma by Peripheral Blood Mononuclear Cells of Patients with Seasonal Allergic Rhinitis due to Japanese Cedar Pollens

This study comprised 130 adult patients with Japanese cedar pollen-specific IgE in the serum and 15 non-atopic individuals. Eighteen patients had no seasonal aggravation of nasal symptoms during the pollen season in 1998 (asymptomatic group). Forty-two patients had not been treated previously with immunotherapy and were treated with antihistamine tablets during the pollen season in 1998 (medication group). Sixty-one patients had undergone variable periods of immunotherapy using pollen extracts, and they were further divided into a good-IT group who responded markedly to immunotherapy and a poor-IT group who responded poorly to immunotherapy. The remaining nine patients had been treated with immunotherapy for more than 12 years and all of them had stopped immunotherapy by the end of May 1997 because they had no nasal symptoms for the last three pollen seasons and were considered to be cured of seasonal allergic rhinitis (cure group). Peripheral blood mononuclear cells (PBMCs) were collected from each subject during the cedar pollen season in 1998 and were stimulated for 96 h with 10 w g/ml Cry j 1. The concentrations of interleukin-5 (IL-5) and interferon-gamma (IFN- n ) in the culture supernatant were determined using an enzyme-linked immunosorbent assay. The levels of IFN- n did not differ significantly among the non-atopic group, the asymptomatic group, the medication group, the poor-IT group and the good-IT group. The level of IL-5 in the asymptomatic group was not different from that in the non-atopic group. The levels of IL-5 in the medication group, the good-IT group and the poor-IT group were significantly higher than in the non-atopic group. The level of IL-5 in the good-IT group, but not in the poor-IT group, was significantly lower than in the medication group. The level of IL-5 in the cure group was not significantly different from in the non-atopic group, and the level of IFN- n in the cure group was significantly lower than in the non-atopic group. In conclusion, immunotherapy can decrease the pollen allergen-induced synthesis of IL-5, but not of IFN- n , and this immunological modulation is involved in the working mechanism of immunotherapy related to its clinical efficacy. A tolerance or anergy of both TH1 and TH2 cells under allergen stimulation may be an immunological indication of cure after the treatment of seasonal allergic rhinitis. Thus, the suppression of synthesis of IL-5 and IFN- n by allergen-stimulated PBMCs is likely to be a reliable criterion for a possible cure of seasonal allergic rhinitis after immunotherapy.

Seasonal Changes in Phytohemagglutinin-induced Cytokine Synthesis by Peripheral Blood Lymphocytes of Patients with Seasonal Allergic Rhinitis due to Japanese Cedar Pollens

We investigated the seasonal changes in non-specific stimulation-induced cytokine production by peripheral blood mononuclear cells (PBMCs) in patients with seasonal allergic rhinitis due to Japanese cedar pollen. This study included 16 non-allergic healthy adult volunteers and 115 patients with detectable levels of Japanese cedar pollen-specific IgE in their serum. The 115 patients were divided into five groups, an asymptomatic group (specific IgE was positive but there were no nasal symptoms), a medication group (typical symptoms of Japanese cedar pollinosis and treated with antihistamine tablets), a good-IT group (responded well to immunotherapy), a poor-IT group (responded poorly to immunotherapy) and a cure group (no symptoms after discontinuation of immunotherapy). PBMCs (1.0 2 10 6 cells/ml) were collected before and during the cedar pollen season in 1998, and were cultured for 24 h in the presence of 10 w g/ml phytohemagglutinin. The concentrations of IL-4, IL-5 and IFN- n in the culture supernatants were measured by an enzyme-linked immunosorbent assay. None of the levels of IL-4, IL-5 and IFN- n synthesized by PBMCs in the asymptomatic group, medication group, good-IT group, poor-IT group or cure group were significantly different from those in the non-atopic group. In the medication group, the synthesis of TH2-type cytokines (both IL-4 and IL-5), but not of TH1-type cytokine (IFN- n ) was significantly increased during the pollen season compared with before the pollen season, whereas in the non-atopic group, the synthesis of IL-4, IL-5 and IFN- n did not differ significantly before and during the pollen season. The synthesis of both IL-4 and IL-5 was significantly increased during the pollen season in the poor-IT group, whereas the synthesis of IL-4 and IL-5 was not increased during the pollen season in the good-IT or cure groups. In conclusion, our study demonstrates that T-cell reactivity to non-specific stimulation outside of the pollen season did not differ between the patients with seasonal allergic rhinitis and non-atopic individuals, that T-cells in patients with seasonal allergic rhinitis are affected or primed by the natural pollen exposure to synthesize TH2-type cytokines even in response to non-specific stimulation, and that successful immunotherapy could decrease the natural pollen exposure-primed hyperreactivity of TH2 cells to non-specific stimulants.

Yearly and seasonal changes of specific IgE to japanese cedar pollen in a young population.

There have been no detailed long-term observations of the relationship between specific IgE production and stimulation by various naturally occurring allergens. This study was conducted to elucidate the yearly and seasonal changes of specific IgE antibody production to Japanese cedar pollen, an allergen of Japanese cedar pollinosis, in young adults. The number of Japanese cedar pollen were counted over a period of 9 years. Changes in the percentages of antibody carriers to Japanese cedar pollen and mite were examined during these years. Changes in Japanese cedar pollen-specific IgE levels between a low exposure year and a high exposure year in individual subjects were also investigated. From 1987 to 1995, the percentages of Japanese cedar pollen-IgE carriers varied from about 30% to 50% with the intensity of pollen stimulation, and carriers tended to increase yearly. The rates of anti-mite IgE carriers changed little. In the spring which is the pollen season, Japanese cedar pollen-IgE levels in low exposure years were weaker than those in high exposure years in individual subjects. Levels in autumn, which is not the pollen season, showed equivalent levels in both high and low exposure years. Anti-mite IgE levels in individual subjects varied little during these years. A long-term follow-up study supported that Japanese cedar pollen-IgE production is mainly associated with the degree of allergen exposure.