The 1st step initiation essential for allergen-specific IgE antibody production upon the 2nd step: Induction of non-specific IgE+ small B cells containing secondly-sensitized allergen-specific ones in mice firstly-sensitized with an allergen.

There was a significant amount of non-specific, but not of allergen (e.g., papain, mite feces and four kinds of pollen)-specific, IgE antibodies (Abs) in the sera of normal mice. An i.n. injection of each allergen without adjuvant into mice caused an increase in total IgE Ab titers with a similar time course in the serum. However, the stage of initiation of allergy varied from allergen to allergen. Submandibular lymph node cells from normal mice contained papain-, but not mite feces- or pollen-specific IgE+ cells and an i.n. injection of papain induced papain-specific IgE Abs in the serum. In contrast, one (i.n.) or two (i.n. and s.c) injections of mite feces induced neither mite feces-specific IgE+ cells in the lymph nodes nor mite feces-specific IgE Abs in the serum. I.n. sensitization with cedar pollen induced cedar pollen-specific IgE+ small B cells in the lymph nodes on Day 10, when non-specific IgE Ab titers reached a peak in the serum, implying induction of related allergen-specific IgE+ small cells as well. In fact, a second (s.c.) injection of ragweed (or cedar) pollen into mice sensitized i.n. once with cedar (or ragweed) pollen, but not with mite feces, induced a large amount of ragweed (or cedar) pollen-specific IgE Abs in the serum. These results indicate that when firstly-sensitized non-specific IgE+ small B cells in mouse lymph nodes include some secondly-sensitized allergen-specific ones, mice produce IgE Abs specific for the secondly-injected allergen.

A retrospective study of 231 Japanese vitiligo patients with special reference to phototherapy.

Although the outcomes of various treatment modalities for vitiligo have been studied extensively, the influence of the participant's characteristics on treatment response has not been thoroughly investigated. Therefore, we retrospectively investigated treatment effects and their association with clinical characteristics in Japanese patients with vitiligo. The charts of patients with vitiligo treated in our institution were reviewed. Clinical response was evaluated as a marked response rate, defined as repigmentation in >75% of the initial lesional area. 162 patients were treated with phototherapy, while 69 were treated with topical mono-therapy. The patients treated with phototherapy and those treated with both phototherapy and topical treatment demonstrated significantly higher clinical response rates compared to patients treated solely with topical mono-therapy (marked response rate: 19.1% vs. 5.8%, P<0.05; and 23.5% vs. 5.8%, P<0.01, respectively). Among the phototherapy-treated patients, younger subjects (≤15 years old) were more responsive to phototherapy compared to older patients (37.0% vs. 15.6%; P=0.015). The disease subtypes did not affect treatment response. In conclusion, phototherapy appears to have a therapeutic effect superior to topical mono-therapy on both focal and generalized vitiligo, especially in younger patients. Thus, any type of psychosocially devastating lesions in a pediatric patient may be a good target for phototherapy.

Continuous 6-year follow-up study of sensitization to Japanese cedar pollen and onset in schoolchildren.

BACKGROUND: Intra individual longitudinal data has been lacking for IgE-mediated seasonal allergic rhinitis (SAR), especially in young children. Little is known about the development and natural course of SAR in terms of prevalence and incidence rates in schoolchildren. METHODS: In May or June each year from 1994 to 2007, schoolchildren were assessed for serum Japanese cedar pollen (JCP)-IgE and house dust mite (HDM)-IgE levels, and surveyed regarding nasal symptoms. RESULTS: Among the 220 children initially assessed in the first grade, 69 (31.4%) were already sensitized to JCP at first grade and 119 (54.1%) did not develop JCP sensitivity during the 6-year study at all. In the first grade children who were HDM-sensitized but JCP non-sensitized, JCP-IgE level was significantly elevated compared to the JCP and HDM non-sensitized group. This seems to indicate that HDM sensitization was very strongly associated with JCP sensitization. CONCLUSIONS: Elevated serum IgE is a consequence of specific sensitization to HDM and HDM sensitization appeared to develop prior to the start of primary school which distinguishes HDM sensitization from JCP sensitization.

Essential role of macrophages in the initiation of allergic rhinitis in mice sensitized intranasally once with cedar pollen: regulation of class switching of immunoglobulin in B cells by controlling interleukin-4 production in T cells of submandibular lymph nodes.

The production of allergen-specific IgE antibodies (Abs) in allergen-sensitized patients or animals has a mutual relationship with the immunologic response leading to allergic rhinitis. We recently reported that, after an intranasal injection of cedar pollen into mice, an interleukin-4 (IL-4)-dependent increase in serum nonspecific IgE Abs was a prerequisite for the production of serum allergen-specific IgE Abs. Here, we explored which lymphoid organs were responsive to the intranasally injected allergen and how IL-4 and IgE Abs were produced in the lymphocytes. Time-dependent changes in the total cell numbers and in in vitro IgE Ab production in various lymphoid organs revealed that the submandibular lymph nodes were the main responsible organ. After treatment with allergen (for IgE production) or allergen and complete Freund's adjuvant (for IgG production), we separated submandibular lymph node cells into macrophage-, lymphocyte-, and granulocyte-rich populations by discontinuous Percoll density-gradient centrifugation. Unexpectedly, bulk cells, but not the lymphocyte- or macrophage-rich populations, produced significant amounts of IL-4, IgE, and IgG; whereas production was restored by addition of Mac-1(+) cells from the macrophage-rich to the lymphocyte-rich fraction. Furthermore, a combination of the lymphocyte-rich population (for IgG [or IgE]) production) and the macrophage-rich population (for IgE [or IgG]) production) produced a large amount of IgE (or IgG). These results indicate that, in the initiation of allergic rhinitis, macrophages in the submandibular lymph nodes are essential not only for IL-4 or immunoglobulin production, but also for class switching of immunoglobulin in lymphocytes.

Examination, diagnosis and classification for Japanese allergic rhinitis: Japanese guideline.

Many countries throughout the world have experienced an increase in the prevalence of allergic rhinitis (AR), which has come to be a major cause of morbidity in developed countries. The pathology underlying AR is regarded as IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the most common allergic disease, has become a salient public health challenge. Almost all primary care physicians and otorhinolaryngologists have been consulted by AR patients between February and April. Although most such patients have received treatment, numerous patients with AR have not received proper examinations for AR. Clinical guidelines are systematically developed statements that are designed to help practitioners make decisions about appropriate and effective health care. Guidelines in many countries including Japan have been published for AR. Unfortunately, those guidelines have remained untested. Moreover, they might be difficult for non-specialists to use. In this review, we specifically examine the present standard examination for diagnosis of AR and optimal classification for AR in Japan. We hope that this review would be used not only for the support of daily practice but also for selection of AR patients for clinical trials.

Evaluating the effects of testing period on pollinosis symptoms using an allergen challenge chamber.

BACKGROUND: We previously built a pollen challenge test unit (allergen challenge chamber: ACC) to collect objective data about Japanese cedar pollinosis. In this study, we investigated adequate conditions for pollen challenge using the ACC. METHODS: The study consisted of two parts. The first part was conducted in November, which is not in pollen season. Subjects were exposed to Japanese cedar pollen at a concentration of 50,000 grains/m3 in the chamber for 120 min each day over the course of three consecutive days. The second part was conducted in April, which is just after pollen season. Subjects were exposed to Japanese cedar pollen at the same concentration (50,000 grains/m3) in the chamber for 90 min on a single day. Subjects recorded nasal and ocular symptoms before challenge and every 15 min after challenge initiation. The minimum cross-sectional area in the nasal cavity was measured using acoustic rhinometry before and after challenge as an indicator of nasal obstruction. Inflammatory markers in nasal lavage fluid and serum were also measured before and after challenge. RESULTS: Nasal and ocular symptoms were significantly exacerbated after challenge on all days of the single and 3-consecutive-day challenge tests, particularly on the third day of the consecutive challenge test. Nasal and ocular symptoms were also quickly induced with challenge immediately after the end of pollen season. No significant changes in inflammatory markers were seen. CONCLUSIONS: Care is needed with regard to pollen challenge conditions in the ACC, including timing of the challenge, to induce pollinosis symptoms that accurately reflect chronic inflammation.

Allergic potency of Japanese cedar pollen Cry j 1 is reduced by a low concentration of hypochlorous acid generated by electolysis.

BACKGROUND: Although Japanese cedar (Cryptomeria japonica) pollinosis has developed into a health problem, few methods eradicate indoor allergens completely. In a recent study, however, the effectiveness of inactivation with sodium hypochlorite (NaOCl) treatment was revealed. Therefore, the present study aimed to elucidate the ability of chlorine bleach (NaOCl) to reduce the immunogenicity of the major allergenic protein of Japanese cedar (Cry j 1). METHODS: Sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, enzyme-linked immunosorbant assay, and skin testing were carried out in 7 individuals. RESULTS: The allergenic protein was undetectable using sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver staining at a sodium hypochlorite/allergenic protein molar ratio of 457. Western blotting with human sera showed the same dose-dependent efficacy. The immunogenicity of the purified protein and cedar pollen was also demonstrated on enzyme-linked immunosorbant assay to be reduced by sodium hypochlorite treatment in a dose- and time-dependent manner. Moreover, sodium hypochlorite-treatment inhibited the skin test response to the protein in all 7 individuals. CONCLUSIONS: Hypochlorous acid generated by electrolysis is an effective method for significantly reducing the immunogenicity of Cry j 1.

IL-4-dependent induction of IgE basophils in peripheral blood and IgE B cells in spleen as respective indicators of allergen sensitization and a precursor of cells secreting allergen-specific IgE antibody.

It was recently reported by us that either primary i.n. or i.p. injection of cedar pollen extract into BALB/c mice, or a second s.c. injection of the allergen into i.v. or s.c. sensitized mice, causes an IL-4-dependent increase in total IgE serum antibody to produce allergen-specific IgE antibody upon further s.c. sensitization. To determine the biology of total IgE antibody, in the present study IgE+ cells in peripheral blood or lymphoid tissues of allergen-sensitized BALB/c mice have been characterized. In peripheral blood, mice sensitized one to three times with the allergen produced a 2.5- to 4-fold increase in the number of IgE+ cells, with a time-course similar to that of the concentration of total IgE antibody in serum. These IgE+ cells were basophils. On the other hand, the number of IgE+ cells in the lymphoid tissues did not change significantly after an i.n., i.p., i.v. or s.c. injection of allergen into the mice, whereas a second s.c. injection of the allergen into the i.v.-, but not into the i.n.-, i.p.- or s.c.-, sensitized mice induced a small number of IgE+/IgM+/B220+ B cells in the spleen. In contrast, IgE+ cells were not seen in the blood or spleen of IL-4 -/- mice after sensitization with the allergen. These results suggest that IgE+ basophils in the peripheral blood, and IgE+ B cells in the spleen, might be IL-4-dependently induced as an indicator of sensitization with allergen, and a precursor of cells secreting allergen-specific IgE antibody, respectively.

Effect of local nasal immunotherapy on nasal blockage in pollen-induced allergic rhinitis of Guinea pigs.

BACKGROUND: As a non-injection route for immunotherapy, local nasal immunotherapy has been examined in allergic rhinitis patients. However, it is unclear how the immunotherapy affects sneezing, biphasic nasal blockage and nasal hyperresponsiveness. Thus, we evaluated the therapeutic effects of nasal immunotherapy on the symptoms of guinea pig allergic rhinitis. Additionally, we also evaluated whether the immunotherapy relieved pollen-induced allergic conjunctivitis. METHODS: Sensitized animals were repeatedly challenged by pollen inhalation once every week. After the 7th challenge, the pollen extract was intranasally administered 6 times a week until the 30th challenge. Sneezing frequency was counted after each of the challenges. As an indicator of nasal blockage, changes in specific airway resistance were measured. Nasal hyperresponsiveness was assessed by measuring leukotriene D(4)-induced nasal blockage. Additionally, during the immunotherapy, we applied pollen onto the ocular surface to induce the allergic conjunctivitis symptoms. RESULTS: At the 11th-30th challenges, the nasal immunotherapy showed inhibition or a tendency to inhibit the biphasic nasal blockage although the inhibitions were variable at respective challenges. The development of nasal hyperresponsiveness was markedly suppressed by the immunotherapy. Nevertheless, neither sneezing nor antigen-specific IgE antibody production was substantially influenced by the immunotherapy. On the other hand, the nasal immunotherapy did not affect the induction of allergic conjunctivitis symptoms. CONCLUSIONS: Local nasal immunotherapy may be clinically useful for allergic nasal blockage associated with nasal hyperresponsiveness. The mechanisms responsible for this effectiveness might not be related to IgE production. Additionally, the effectiveness for nasal tissue was dissociated from that seen for the ocular tissue.

A 13-year study of Japanese cedar pollinosis in Japanese schoolchildren.

BACKGROUND: Japanese cedar pollen (JCP) sensitization and Japanese cedar pollinosis (JCPS) appear to be increasingly prevalent in younger children. The present study investigated factors affecting JCP sensitization and JCPS development in school children. METHODS: In May or June each year from 1994 to 2006, 275-510 children were assessed for serum JCP-IgE and house dust mite (HDM)-IgE levels, and surveyed regarding rhinoconjunctival symptoms. RESULTS: Strong JCP sensitization (IgE > or = 17.5 U(A)/ml) was associated with age (odds ratio (OR) = 2.65), the amount of dispersed pollen in the observed year (OR = 2.03) and in the year following birth (OR = 1.51), the month of birth (OR = 2.18), and the recent birth cohort (OR = 1.96). Symptoms were negatively correlated with the recent birth cohort (OR = 0.69) after adjusting for JCP-IgE levels. Strong HDM sensitization was associated with gender (OR = 0.65 for girls) and the recent birth cohort (OR = 1.76). CONCLUSIONS: JCP sensitization appeared to be associated with the recent birth cohort and to increases in dispersed pollen just after birth and in the observed season. Although the recent birth cohort was more easily sensitized, they were not more likely to develop symptoms. In contrast to JCP sensitization, strong HDM sensitization appeared to develop prior to commencement of primary school and was more likely to affect boys.

Essential role of monocytes in the in vitro production of IL-4 and nonspecific IgE antibody by peripheral blood lymphocytes from mice sensitized s.c. once with cedar pollen.

To explore which cytokine or cell is essential for the production of antibodies (Abs) of the IgE class in allergic diseases, we injected cedar pollen into wild-type, interferon-gamma(-/-) (IFN-gamma(/)), or interleukin-4(-/-) (IL-4(-/-)) BALB/c mice through four (i.n., i.p., s.c., and i.v.) different routes without adjuvant. Wild-type or IFN-gamma(-/-), but not IL-4(-/-), mice sensitized once or twice showed a significant increase in total IgE Ab in their serum, revealing the essential role of IL-4 in the production of total IgE Ab. We separated peripheral blood mononuclear cells (PBMCs) from untreated or sensitized mice into monocyte-rich, lymphocyte-rich, and granulocyterich populations by Percoll density-gradient centrifugation or into specific antigen cells by flow cytometry, cultured the cells in various combinations, and examined the levels of cytokines and IgE Ab released into the medium. The PBMCs from mice sensitized s.c. once, but not those from untreated animals, produced significant amounts of IL-4 and total IgE Ab, whereas the lymphocyte-rich population alone did not. Unexpectedly, IL-4 and IgE Ab production was restored by the addition of Mac-1(+) cells in the monocyte-rich fraction to the lymphocyte-rich fraction. These results indicate the essential role of monocytes in the production of IL-4 and total IgE Ab by lymphocytes during the initial stage of sensitization.

Effect of oral immunotherapy on nasal blockage in experimental allergic rhinitis.

We previously reported that when Japanese cedar pollen was prophylactically p.o. administered before a sensitization stage in a guinea-pig model of allergic rhinitis, pollen-induced nasal blockage was suppressed. In this study, we evaluated whether the oral immunotherapy is also effective when the pollen extract was administered starting from the day when the nasal blockage was clearly induced and whether the effectiveness continued after cessation of the immunotherapy. Sensitized animals were repeatedly challenged by pollen inhalation once every week. After the 7th challenge, the extract was orally administered twice a week until the 30th challenge. At the 11th challenge, the oral immunotherapy showed inhibition of the biphasic nasal blockage. The effectiveness was consistently observed during the immunotherapy until the 30th challenge. Furthermore, the increased nasal responsiveness to intranasal application of leukotriene D4 was markedly suppressed by the immunotherapy. Interestingly, even after cessation of the therapy, inhibition of the nasal blockage was sustained for more than 2 months. Nevertheless, neither sneezing nor antigen-specific IgE antibody production was substantially influenced by the immunotherapy. In conclusion, Oral immunotherapy may be clinically useful for allergic nasal blockage. Mechanisms underlying the effectiveness may be associated with the hyporesponsiveness of the nasal mucosa to released mediators.

IgE production after four routes of injections of Japanese cedar pollen allergen without adjuvant: crucial role of resident cells at intraperitoneal or intranasal injection site in the production of specific IgE toward the allergen.

The production of specific IgE antibodies directed toward cedar pollen correlates well with the onset of allergic rhinitis; but the mechanisms of allergen recognition as nonself and Ig class switch to IgE by the immune system are still not fully understood. In the present study, we injected cedar pollen into mice through 4 different routes (intranasal (i.n.), intraperitoneal (i.p.), intravenous (i.v.), and subcutaneous (s.c.)) without adjuvant 1 to 3 times, and determined time-dependent changes in the total and specific serum IgE levels compared with those in the serum levels of other isotype Igs. After an i.p. or i.n. injection of allergen into the mice, they produced a 1.5-to 1.7-fold increase in total IgE, but none in IgG, IgM, or IgA antibodies in their serum, whereas an i.v. or s.c. injection of allergen was inactive as an inducer of total IgE antibodies. Upon a 2nd (s.c.) injection of the allergen into the i.p. or i.n. sensitized mice, a large amount of allergen-specific IgE antibodies was found in the serum. In the case of i.v. or s.c. sensitized mice, however, they produced total, but not specific, IgE antibodies; and a 3rd (s.c.) injection of the allergen resulted in a large amount of specific IgE antibodies in the serum. These results imply that resident cells at the i.p. or i.n. injection site may play a crucial role in the efficient production of total and specific IgE antibodies toward the allergen.

The efficacy of short-term administration of 3 antihistamines vs placebo under natural exposure to Japanese cedar pollen.

BACKGROUND: Japanese cedar pollinosis, a common disease with morbidity of approximately 20% in the Japanese population, is characterized by subjectively irritating symptoms during an annual 3-month period. OBJECTIVE: To investigate the effectiveness of cetirizine hydrochloride, loratadine, and fexofenadine hydrochloride in reducing pollinosis symptoms induced while walking in a park during the pollen season. METHODS: A randomized, double-masked, placebo-controlled trial was conducted in 113 individuals with Japanese cedar pollinosis during 2 days in March 2003 in Osaka Expo Park, Osaka, Japan. Participants (aged 20-57 years) were divided into 4 groups according to treatment assignment: cetirizine hydrochloride, 10 mg/d; fexofenadine hydrochloride, 120 mg/d; loratadine, 10 mg/d; and placebo (lactose), twice daily. Symptoms were recorded hourly during the study. Furthermore, all the patients completed the Japanese version of the Rhinoconjunctivitis Quality of Life Questionnaire before and after the trial. RESULTS: Self-evaluated symptom scores in all 3 active treatment groups showed significant improvements compared with the placebo group. Furthermore, the cetirizine group showed significant improvement in the domains of frequency of nose blowing and nasal obstruction compared with placebo. In addition, improvement in Japanese Rhinoconjunctivitis Quality of Life Questionnaire scores was higher in the cetirizine group than in the loratadine and placebo groups. CONCLUSION: Cetirizine seems to be more effective than fexofenadine and loratadine at reducing subjective symptoms in this study population.

Kinins are involved in the development of allergic nasal hyperresponsiveness in guinea pigs.

We evaluated roles of kinins in allergen-induced nasal blockage and sneezing, and development of nasal hyperresponsiveness to leukotriene D4 in a Japanese cedar pollen-induced allergic rhinitis model of guinea pigs. Sensitised guinea pigs were repeatedly challenged by pollen inhalation once every week. Neither a bradykinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin nor a bradykinin B2 receptor antagonist, icatibant suppressed allergen-induced sneezing and nasal blockage. However, development of nasal hyperresponsiveness to leukotriene D4 was significantly suppressed by them. The amount of bradykinin in nasal cavity lavage fluid was immediately increased after the challenge. In non-sensitised animals, hyperresponsiveness to leukotriene D4 was developed by a bradykinin B2 receptor agonist, bradykinin, but not by a bradykinin B1 receptor agonist, des-Arg10-kallidin, while in the sensitised-challenged animal, both agonists developed hyperresponsiveness. In conclusion, the nasal hyperresponsiveness appeared to be induced by kinins produced in response to the antigen challenge through activation of not only bradykinin B2 but also B1 receptors.

Acquired nasal hyperresponsiveness aggravates antigen-induced rhinitis in the guinea pig.

Whether a state of nasal hyperresponsiveness influences antigen-induced biphasic nasal blockage and sneezing were examined using a guinea pig model of allergic rhinitis. Sensitized animals were challenged with an antigen, Japanese cedar pollen, once every week. Before the 13th challenge, the animals were randomly divided into 2 groups, and then the 13th challenge was performed (Groups A-0 and B-0). The 14th challenge was done on day 2 (Group A-2) and on day 7 (Group B-7) after the 13th challenge, on which nasal hyperresponsiveness was present and absent, respectively. Biphasic nasal blockage and sneezing after the challenge in Group A-2 were more severe than those in Group A-0, while those of Group B-7 were almost the same as those of Group B-0. An anti-histaminic, mepyramine, inhibited sneezing but not the biphasic nasal blockage in Group B-7. A cysteinyl leukotriene (CysLT) antagonist, pranlukast, suppressed the late nasal blockage but not the early blockage and sneezing in Group B-7. In contrast, in Group A-2, mepyramine significantly attenuated not only sneezing but also the early nasal blockage. Pranlukast significantly inhibited both nasal blockage and sneezing in Group A-2. In conclusion, nasal hyperresponsiveness aggravated the antigen-induced nasal responses, to which histamine and CysLTs considerably contributed.

[Clinical study of the paranasal sinuses of patients with Japanese Cedar pollinosis].

To clarify paranasal sinus change in patients with Japanese cedar pollinosis, we studied reactions to medical treatment via X-ray images of patients during the 2000 cedar pollen season. Medication was administered to 577 patients consulting facilities in 3 regions--Kyoto, Fukui and Osaka--having different pollen counts i.e., 4555/cm2 in Fukui, 801/cm2 in Kyoto and 531/cm2 in Osaka. The paranasal sinus was X-rayed by Water's method, and the degree of positivity was classified by Katagiri'shadow classification. Patients were grouped into 334 suffering extensive Fukui pollen dispersion and 243 suffering relatively limited Kyoto and Osaka pollen dispersion. At 3-4 weeks after pollen dispersion, contrast shadow positivity was 22.2%, with no difference before pollen dispersion (22.2%) in Kyoto and Osaka. In Fukui, positivity was 39.7%, a clear increase over pre pollen dispersion (19.2%). In the initial treatment group, positivity was 25.8% in Fukui and 28.6% in Kyoto and Osaka. Our results suggest that the incidence of sinusitis in patients with Japanese cedar pollinosis tended to increase with exposure to extensive pollen dispersion and to be suppressed by initial treatment.

Prevalence of Japanese cedar pollinosis among schoolchildren in Japan.

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.