Biochemical composition of Phleum pratense pollen grains: A review.

The Poaceae family is composed of 12,000 plant species. Some of these species produce highly allergenic anemophilous pollen grains (PGs). Phleum pratense pollen grains (PPPGs) emerged as a model for studies related to grass allergy. The biochemical composition of allergenic PGs has not yet been fully described despite potential health effects of PG constituents other than allergenic proteins. This review brings together the information available in literature aiming at creating a comprehensive picture of the current knowledge about the chemical composition of allergenic PGs from timothy grass. PPPGs have an average diameter between 30-35 µm and the mass of a single PG was reported between 11 and 26 ng. The pollen cytoplasm is filled with two types of pollen cytoplasmic granules (PCGs): the starch granules and the polysaccharide particles (p-particles). Starch granules have a size between 0.6-2.5 µm with an average diameter of 1.1 µm (estimated number of 1000 granules per PG) while p-particles have a size ranging around 0.3 to 0.4 µm (estimated number between 61,000-230,000 p-particles per PG). The rupture of PG induces the release of PCGs and the dispersion of allergens in the inhalable fraction of atmospheric aerosol. PPPGs are composed of sporopollenin, sugars, polysaccharides, starch, glycoproteins (including allergens), amino-acids, lipids, flavonoids (including isorhamnetin), various elements (the more abundant being Si, Mg and Ca), phenolic compounds, phytoprostanoids, carotenoids (pigments) metals and adsorbed pollutants. PPPG contains about a hundred different proteins with molecular masses ranging from 10 to 94 kDa, with isoelectric points from 3.5-10.6. Among these proteins, allergens are classified in eleven groups from 1 to 13 with allergens from groups 1 and 5 being the major contributors to Phl p pollen allergy. Major allergen Phl p 5 was quantified in PPPGs by several studies with concentration ranging from 2.7 and 3.5 µg.mg-1 in unpolluted environment. Values for other allergens are scarce in literature; only one quantitative assessment exists for allergen groups Phl p 1, 2 and 4. The extractible lipid fraction of PPPGs is estimated between 1.7-2.2% of the total PG mass. The main chemical families of lipids reported in PPPGs are: alkanes, alkenes, alcohols, saturated and unsaturated fatty acids, di- and tri-hydroxylated fatty acids, aldehydes and sterols. Several lipid compounds with potential adjuvant effects on allergy have been specifically quantified in PPPGs: E2-like prostaglandin (PGE2), B4-like leukotriene (LTB4), unsaturated fatty acids (linoleic and linolenic acids and their hydroxylated derivatives), adenosine, vitamins and phenolic compounds. Some other biochemical characteristics such as NAD(P)H oxidase, protease activity and pollen microbiome were described in the literature. The bioaccessibility in physiological conditions has not been described for most biochemicals transported by allergenic PPPGs. There is also a considerable lack of knowledge about the potential health effects of pollen constituents other than allergens. The variability of pollen composition remains also largely unknown despite its importance for plant reproduction and allergy in an environment characterized by chemical pollution, climate change and loss of biodiversity.

Depletion of CD56+CD3+ invariant natural killer T cells prevents allergen-induced inflammation in humanized mice.

BACKGROUND: CD56-expressing natural killer (NK) cells as well as invariant NK T (iNKT) cells have been shown to either promote or inhibit allergic immune responses. OBJECTIVE: The aim of the present study was to investigate the impact of these cells in a recently developed humanized mouse model of allergen-induced IgE-dependent gut and lung inflammation. METHODS: Nonobese diabetic-severe combined immunodeficiency γ-chain knockout mice were injected intraperitoneally with human PBMCs or CD56-depleted (CD56neg) PBMCs from highly sensitized donors with birch or grass pollen allergy together with the respective allergen or with NaCl as a control. Three weeks later, the mice were challenged with the allergen rectally and gut inflammation was monitored by video miniendoscopy and by histology. Furthermore, airway inflammation was measured after an additional intranasal allergen challenge. RESULTS: Allergen-specific human IgE in mouse sera, detectable only after coinjection of the respective allergen, was reduced in mice being injected with CD56neg PBMCs compared with in mice receiving nondepleted PBMCs. Consequently, allergen-induced IgE-dependent colitis, airway hyperreactivity, and mucus-producing goblet cells were significantly inhibited in these mice. Interestingly, reconstitution of CD56neg PBMCs with nondepleted CD56+ cells and with CD56+CD3+ iNKT cells restored gut as well as lung inflammation, whereas addition of CD3-depleted CD56+ cells did not. CONCLUSION: These results demonstrate that allergen-specific gut and lung inflammation in PBMC-engrafted humanized mice is promoted by CD56+CD3+ iNKT cells, which opens new possibilities of therapeutic intervention in allergic diseases.

Repetitive nasal allergen challenge in allergic rhinitis: Priming and Th2-type inflammation but no evidence of remodelling.

BACKGROUND: Local tissue eosinophilia and Th2 cytokines are characteristic features of seasonal allergic rhinitis. Airway remodelling is a feature of asthma whereas evidence for remodelling in allergic rhinitis (AR) is conflicting. OBJECTIVE: By use of a novel human repetitive nasal allergen challenge (RAC) model, we evaluated the relationship between allergic inflammation and features of remodelling in AR. METHODS: Twelve patients with moderate-severe AR underwent 5 alternate day challenges with diluent which after 4 weeks were followed by 5 alternate day challenges with grass pollen extract. Nasal symptoms, Th1/Th2 cytokines in nasal secretion and serum were evaluated. Nasal biopsies were taken 24 hours after the 1st and 5th challenges with diluent and with allergen. Sixteen healthy controls underwent a single challenge with diluent and with allergen. Using immunohistochemistry, epithelial and submucosal inflammatory cells and remodelling markers were evaluated by computed image analysis. RESULTS: There was an increase in early and late-phase symptoms after every allergen challenge compared to diluent (both P < .05) with evidence of both clinical and immunological priming. Nasal tissue eosinophils and IL-5 in nasal secretion increased significantly after RAC compared to corresponding diluent challenges (P < .01, P = .01, respectively). There was a correlation between submucosal mast cells and the early-phase clinical response (r = 0.79, P = .007) and an association between epithelial eosinophils and IL-5 concentrations in nasal secretion (r = 0.69, P = .06) in allergic rhinitis. No differences were observed after RAC with regard to epithelial integrity, reticular basement membrane thickness, glandular area, expression of markers of activation of airway remodelling including α-SMA, HSP-47, extracellular matrix (MMP7, 9 and TIMP-1), angiogenesis and lymphangiogenesis for AR compared with healthy controls. CONCLUSION: Novel repetitive nasal allergen challenge in participants with severe persistent seasonal allergic rhinitis resulted in tissue eosinophilia and increases in IL-5 but no structural changes. Our data support no link between robust Th2-inflammation and development of airway remodelling in AR.

Age-of-onset information helps identify 76 genetic variants associated with allergic disease.

Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P<3x10-8) with age-of-onset. Forty-five variants had comparable effects on the onset of the three individual diseases and 38 were also associated with allergic disease case-control status in an independent study (n = 222,484). We observed a strong negative genetic correlation between age-of-onset and case-control status of allergic disease (rg = -0.63, P = 4.5x10-61), indicating that cases with early disease onset have a greater burden of allergy risk alleles than those with late disease onset. Subsequently, a multivariate GWAS of age-of-onset and case-control status identified a further 26 associations that were missed by the univariate analyses of age-of-onset or case-control status only. Collectively, of the 76 variants identified, 18 represent novel associations for allergic disease. We identified 81 likely target genes of the 76 associated variants based on information from expression quantitative trait loci (eQTL) and non-synonymous variants, of which we highlight ADAM15, FOSL2, TRIM8, BMPR2, CD200R1, PRKCQ, NOD2, SMAD4, ABCA7 and UBE2L3. Our results support the notion that early and late onset allergic disease have partly distinct genetic architectures, potentially explaining known differences in pathophysiology between individuals.

Frequency and clinical features of pollen-food syndrome in children.

BACKGROUND: Pollen-food syndrome (PFS) is an allergic reaction to fresh fruits, vegetables and/or nuts that can occur in patients who are allergic to pollen. The prevalence of PFS in children is not clearly known. OBJECTIVE: The objective of this study was to determine the frequency and clinical features of PFS in pediatric patients with pollen-induced allergic rhinitis (AR). METHOD: This study was conducted in the pediatric allergy outpatient clinic of our hospital. Pollen-induced seasonal AR patients who were evaluated for any symptoms appearing after consuming any fresh fruits and vegetables. RESULTS: Six hundred and seventy-two pollen-sensitized patients were included in this study. The symptoms related to PFS were reported in 22 (3.3%) patients. The median age of the patients was 12.3 years and 59% (n=13) were female. Peach was the most common culprit (22%). There were isolated oropharyngeal symptoms in 20 (91%) patients and anaphylaxis in two (9%) patients with the suspected food. The multiple logistic regression analysis revealed that female gender, history of atopic dermatitis and allergic diseases in the family were the potential risk factors for PFS [Odds ratio 95%CI: 3.367 (1.344-8.435), 5.120 (1.935-13.550), 3.046 (1.239-7.492), respectively]. CONCLUSION: PFS can be seen in children who are followed up for pollen-induced AR. The symptoms of PFS are usually mild and transient. However, comprehensive evaluation of patients is important since serious systemic reactions such as anaphylaxis can also be observed.

Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses.

BACKGROUND: IgE is the least abundant immunoglobulin and tightly regulated, and IgE-producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood. OBJECTIVE: The cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT) were investigated. METHODS: In a randomized double-blind, placebo-controlled, time course SLIT study, PBMCs and nasal biopsy samples were collected from 40 adults with seasonal allergic rhinitis at baseline and at 4, 8, 16, 28, and 52 weeks. RNA was extracted from PBMCs, sorted B cells, and nasal biopsy samples for heavy chain variable gene repertoire sequencing. Moreover, mAbs were derived from single B-cell transcriptomes. RESULTS: Combining heavy chain variable gene repertoire sequencing and single-cell transcriptomics yielded direct evidence of a parallel boost of 2 clonally and functionally related B-cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells. Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relatively stable as per heavy chain isotype, somatic hypermutations, and clonal composition. Single IgGE+ memory B-cell and IgE+ preplasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and able to elicit basophil activation at very low allergen concentrations. CONCLUSION: For the first time, we have shown that on mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These cells rapidly switch isotype, expand into short-lived IgE+ plasmablasts, and serve as a potential target for therapeutic intervention.

Pollen Allergy Suppression Effect by the Oral Administration of Acetic Acid Bacteria (Gluconacetobacter hansenii).

BACKGROUND/AIM: Gluconacetobacter hansenii (G. hansenii) is an acetic acid bacterium of vinegar production. Its anti-allergic effect on mice upon oral administration was examined. MATERIALS AND METHODS: The amount of LPS was measured by the Limulus reaction. Mice were sensitized by peritoneal and intranasal administration of cedar pollen and alum followed by oral administration of 30 or 150 mg/kg of heated G. hansenii cells. Pollen was administered intranasally to evaluate nasal symptoms, and at 8 weeks, IgE and IL-10 levels in blood were measured by ELISA. RESULTS: The amount of LPS in dried bacterial cells was 10.4±3.3 mg/g. In the cedar pollinosis model of mice, a significant reduction was observed in nose scratching of both groups administered with the bacterial cells (30, 150 mg/kg). CONCLUSION: G. hansenii contains LPS, and its oral administration showed an anti-allergic effect by a significant mitigation of the symptoms in a pollen allergy mouse model.

T-cell activation by transgenic rice seeds expressing the genetically modified Japanese cedar pollen allergens.

Transgenic rice seeds that contain genetically modified Cry j 1 and Cry j 2, the two major allergens of Cryptomeria japonica (Japanese cedar; JC), have been developed as immunotherapeutic candidates for JC pollinosis. Because the transgenic rice (TG-rice) seeds express allergens containing whole amino acid sequences of Cry j 1 and Cry j 2 in the endosperm tissue (edible part of rice grain), they can potentially target all Cry j 1- and Cry j 2-specific T-cells. However, it was unknown whether antigenicity of Cry j 1 and Cry j 2 could be completely preserved in TG-rice seeds. We verified the antigenicity of TG-rice seeds to T-cells through the analysis of the proliferative responses of T-cells in Cry j 1- or Cry j 2-immunized mice or T-cell lines to TG-rice seed extract. First, four mouse strains were immunized with Cry j 1 or Cry j 2. T-cells in the immunized mice proliferated on treatment with TG-rice seed extract, but not non-transgenic wild-type rice (WT-rice) seed extract. Furthermore, T-cell lines were established from the spleen cells of the immunized mice. Each T-cell line resulted in a proliferative response to TG-rice seed extract, but not to WT-rice seed extract, suggesting that TG-rice seeds certainly express T-cell epitopes corresponding to T-cell lines. Considering the modified amino acid sequences of Cry j 1 and Cry j 2 in TG-rice seeds, the expression of specific T-cell epitopes suggested that TG-rice seeds express all possible T-cell epitope repertoires of Cry j 1 and Cry j 2.

Discriminating severe seasonal allergic rhinitis. Results from a large nation-wide database.

Allergic rhinitis (AR) is a chronic disease affecting a large amount of the population. To optimize treatment and disease management, it is crucial to detect patients suffering from severe forms. Several tools have been used to classify patients according to severity: standardized questionnaires, visual analogue scales (VAS) and cluster analysis. The aim of this study was to evaluate the best method to stratify patients suffering from seasonal AR and to propose cut-offs to identify severe forms of the disease. In a multicenter French study (PollinAir), patients suffering from seasonal AR were assessed by a physician that completed a 17 items questionnaire and answered a self-assessment VAS. Five methods were evaluated to stratify patients according to AR severity: k-means clustering, agglomerative hierarchical clustering, Allergic Rhinitis Physician Score (ARPhyS), total symptoms score (TSS-17), and VAS. Fisher linear, quadratic discriminant analysis, non-parametric kernel density estimation methods were used to evaluate miss-classification of the patients and cross-validation was used to assess the validity of each scale. 28,109 patients were categorized into "mild", "moderate", and "severe", through the 5 different methods. The best discrimination was offered by the ARPhyS scale. With the ARPhyS scale, cut-offs at a score of 8-9 for mild to moderate and of 11-12 for moderate to severe symptoms were found. Score reliability was also acceptable (Cronbach's α coefficient: 0.626) for the ARPhyS scale, and excellent for the TSS-17 (0.864). The ARPhyS scale seems the best method to target patients with severe seasonal AR. In the present study, we highlighted optimal discrimination cut-offs. This tool could be implemented in daily practice to identify severe patients that need a specialized intervention.

The Relationship of Pollen Dispersal with Allergy Symptoms and Immunotherapy: Allergen Immunotherapy Improves Symptoms in the Late Period of Japanese Cedar Pollen Dispersal.

BACKGROUND: The severity of symptoms of pollen-induced allergic rhinitis is affected by the amount of scattered pollen. However, the relationships between the pollen dispersal pattern, symptom severity, and treatment efficacy are not clear. METHODS: Between 2007 and 2012, we performed 4 randomized, placebo-controlled studies of sublingual immunotherapy (SLIT) on patients with Japanese cedar-induced allergic rhinitis who lived in or around Chiba, Japan. The participants were asked to avoid using rescue medicines during the cedar pollen season as much as possible and to record their nasal symptoms in allergy diaries. The amount of pollen dispersed daily was quantified using the Durham method, and the season was divided into early and late periods based on the pollen count. RESULTS: A total of 721 patients were enrolled in the 4 studies during the 6-year study period. In the placebo group (n = 349), a correlation was observed between the amount of pollen dispersed and the severity of symptoms in the early but not late period of pollen dispersal. Treatment with SLIT (n = 372) significantly improved symptom severity in the late but not early period. CONCLUSION: For patients with Japanese cedar pollen-induced allergic rhinitis, the fluctuation of daily pollen dispersal had a minimal effect on the severity of symptoms during the late period. SLIT was remarkably effective in alleviating symptoms during this period but not in the early period.

Is eosinophilic esophagitis an equivalent of pollen allergic asthma? Analysis of biopsies and therapy guided by component resolved diagnosis.

BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by esophageal dysfunction and, histologically, by eosinophilic inflammation. There is not a clear etiologic treatment. Biopsies analysis using plant histology methods may show callose and pollen tubes in the esophageal mucosa. Component-resolved diagnosis (CRD) with microarrays could detect possible allergens involved and indicate an elimination diet and allergen immunotherapy (AIT). METHODS: One hundred and twenty-nine patients with EoE were tested for environmental and food allergens. CRD, histological and botanical analysis were performed. Clinical scores and endoscopic biopsy were performed every six months for three years. Fifty healthy patients, 50 asthmatics due to pollen, and 53 celiac disease patients were included as comparison groups. CRD-directed AIT was administered in 91 EoE patients and elimination diet in 140 patients (87 EoE and all 53 CD patients). RESULTS: CRD detected allergen hypersensitivity in 87.6% of patients with EoE. The predominant allergens were grass group 1 (55%), lipid transfer proteins (LTP) of peach and mugwort, hazelnuts and walnuts. Callose from pollen tubes was found in 65.6% of biopsies. After CRD-guided elimination diet and/or AIT, 101 (78.3%) EoE patients showed significant clinical improvement (p<0.017) and 97 (75.2%) were discharged (negative biopsy, no symptoms, no medication) without relapse. AIT-treated patients had better outcomes (odds ratio 177.3, 95% CI 16.2-1939.0). CONCLUSION: CRD-directed AIT and/or elimination diet was efficient in treating EoE patients and was well tolerated.

Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy.

BACKGROUND: Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease. OBJECTIVE: The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet compared with placebo on the risk of developing asthma. METHODS: A total of 812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial, comprising 3 years of treatment and 2 years of follow-up. RESULTS: There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication at the end of trial (odds ratio = 0.66, P < .036), during the 2-year posttreatment follow-up, and during the entire 5-year trial period. Also, grass allergic rhinoconjunctivitis symptoms were 22% to 30% reduced (P < .005 for all 5 years). At the end of the trial, the use of allergic rhinoconjunctivitis pharmacotherapy was significantly less (27% relative difference to placebo, P < .001). Total IgE, grass pollen-specific IgE, and skin prick test reactivity to grass pollen were all reduced compared to placebo. CONCLUSIONS: Treatment with the SQ grass sublingual immunotherapy tablet reduced the risk of experiencing asthma symptoms and using asthma medication, and had a positive, long-term clinical effect on rhinoconjunctivitis symptoms and medication use but did not show an effect on the time to onset of asthma.

Pollen Lipids Can Play a Role in Allergic Airway Inflammation.

In seed plants, pollen grains carry the male gametes to female structures. They are frequent in the ambient air, and cause airway inflammation in one out of four persons in the population. This was traditionally attributed to soluble glycoproteins, leaking into the nasal mucosa or the conjunctiva, and able to bind antibodies. It is now more and more recognized that also other immunomodulating compounds are present. Lipids bind to Toll-like and PPARγ receptors belonging to antigen-presenting cells in the mammal immune system, activate invariant Natural Killer T-cells, and are able to induce a Type 2 reaction in effector cells. They may also mimic lipid mediators from mammal mast cells. Pollen grains have a rich lipodome of their own. Among the lipids that have been associated with an atopic reaction are saturated and unsaturated fatty acids, glycophospholipids, sphingolipids, sterols, and oxylipids, as well as lipopolysaccharides from the microbiome on the pollen surface. Lipids can be ligands to allergenic proteins.

Effect of cigarette smoke on counts of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa in young patients with perennial allergic rhinitis / Efeito do tabagismo nas contagens de células imunorreativas a eotaxina-1 e eosinófilos na mucosa nasal em pacientes jovens com rinite alérgica perene

Abstract Introduction: In teenagers with perennial allergic rhinitis, exposure to tobacco cigarette smoke increases the count of eosinophils in the nasal mucosa; the recruitment of eosinophils arises from the combined action of a number of cellular and molecular signals, including eotaxin. Objective: To assess the effect of exposure to tobacco cigarette smoke on the count of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa of children and teenagers with perennial allergic rhinitis. Methods: In a cross-sectional study, forty-four patients were evaluated (aged 7-19 years old): 22 with and 22 with no exposure to tobacco cigarette smoke. After replying to 2 validated questionnaires, on Asthma and Allergies in Childhood and on the severity of nasal symptoms, nasal mucosal samples were obtained by scraping the middle one-third of the inferior turbinates. Then counts of immunoreactive cells to eotaxin-1 and eosinophils were assessed by immunohistochemistry. Results: Patients with exposure to tobacco cigarette smoke showed higher cell counts of both eotaxin-1 and eosinophils than patients with no exposure to the smoke, with no correlation between the two variables. However, both counts, of eotaxin-1 and eosinophils, were related to the cotinine/creatinine ratio. Conclusions: Exposure to tobacco cigarette smoke can increase eotaxin-1 and the count of eosinophils in the nasal mucosa of young patients with perennial allergic rhinitis.

Resumo Introdução: Em adolescentes com rinite alérgica perene, a exposição à fumaça do cigarro de tabaco aumenta a contagem de eosinófilos na mucosa nasal. O recrutamento de eosinófilos surge da ação combinada de alguns sinais celulares e moleculares, inclusive a eotaxina. Objetivo: Avaliar o efeito da exposição à fumaça do cigarro de tabaco na contagem de células imunorreativas a eotaxina-1 e eosinófilos na mucosa nasal de crianças e adolescentes com rinite alérgica perene. Método: Em um estudo transversal, 44 pacientes foram avaliados (entre sete e 19 anos): 22 com e 22 sem exposição à fumaça do cigarro de tabaco. Depois de responder a dois questionários validados, sobre asma e alergias na infância e sobre a gravidade dos sintomas nasais, as amostras de mucosa nasal foram obtidas por meio de raspagem do terço médio das conchas inferiores. Em seguida, as contagens de células imunorreativas para eotaxina-1 e eosinófilos foram avaliadas por imuno-histoquímica. Resultados: Os pacientes com exposição à fumaça do cigarro de tabaco apresentaram contagens de células mais elevadas tanto para eotaxina-1 como para eosinófilos em comparação com os pacientes sem exposição à fumaça, sem correlação entre as duas variáveis. No entanto, ambas as contagens, de eotaxina-1 e eosinófilos foram relacionadas com a razão cotinina/creatinina. Conclusões: A exposição à fumaça do cigarro de tabaco pode aumentar a eotaxina-1 e a contagem de eosinófilos na mucosa nasal de pacientes jovens com rinite alérgica perene.

Safety and efficacy of short-term oral immunotherapy with Cry j 1-galactomannan conjugate for Japanese cedar pollinosis: a randomized controlled trial.

Current allergen-specific immunotherapy (AIT) for pollinosis requires long-term treatment with potentially severe side effects. Therefore, development of an AIT that is safe and more convenient with a shorter regimen is needed. This prospective, double-blind, placebo-controlled trial randomized 55 participants with Japanese cedar pollinosis (JCP) to active or placebo groups to test the safety and efficacy of short-term oral immunotherapy (OIT) with Cry j 1-galactomannan conjugate for JCP. Mean symptom-medication score as the primary outcome in the active group improved 27.8% relative to the placebo group during the entire pollen season. As the secondary outcomes, mean medication score in active group improved significantly, by 56.2%, compared with placebo during the entire pollen season. Mean total symptom score was similar between active and placebo groups during the entire pollen season. There were no severe treatment-emergent adverse events in the active and placebo groups. Therefore short-term OIT with Cry j 1-galactomannan conjugate is safe, and effective for reducing the amount of medication use for JCP.