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Objective At least 3 years of sublingual immunotherapy (SLIT) is required to achieve long-term clinical tolerance for allergens. However, immunological changes with more than 3 years of SLIT have not yet been elucidated in detail. The present study investigated whether the numbers of regulatory T (Treg) cells and regulatory B (Breg) cells increased with 4 years of SLIT and if these increases correlated with clinical effects for pollinosis. Methods Seven Japanese cedar pollinosis patients received SLIT in 2014 or 2015 and continued treatment until May 2019. In May 2017 and May 2019, peripheral blood mononuclear cells (PBMCs) were collected from the patients, and analyzed by flow cytometer. Results (1) The visual analogue scale (VAS) was significantly higher in 2019 than in 2017. (2) The percentages of Foxp3 + Treg cells, type 1 regulatory T (Tr1) cells, and Breg cells in PBMCs were significantly higher in 2019 than in 2017. (3) The percentage of Foxp3 + Treg cells in PBMCs positively correlated with VAS, whereas those of Tr1 cells and Breg cells did not. Conclusions These results suggest that 4 years of SLIT is needed to achieve sustained increases in Foxp3 + Treg cells, which are closely associated with the efficacy of SLIT.

Automatic pollen images recognition is crucial for pollinosis symptoms prevention and treatment. The problem of pollen recognition can be efficiently solved using deep learning, however neural networks require tens of thousands of images to generalize. At the same time, the existing open pollen images datasets are very small. In this paper, we present a novel open pollen dataset annotated for both detection and classification tasks. Based on our dataset we study learning from a small data using different state-of-the-art approaches. For the detection task we propose to use our new Bayesian RetinaNet network, which models aleatoric uncertainty. We compare it with the baseline RetinaNet and demonstrate that our model allows for higher detection precision. For the classification task we compare the impact of pre-training on the synthetic images from generative adversarial networks (GANs) and metric-based few-shot learning. Namely, we pre-trained our small convolutional neural network and Siamese neural network classifiers on synthetic pollen images generated by two GANs: StyleGAN and Self-attention GAN. The best classifier is the convolutional neural network pre-trained on StyleGAN images. Our best models achieved 96.3% of mean average precision for the detection task and 97.7% of F1 measure for the classification task on 13 pollen plant species. We have implemented the best models in our pollen recognition web service, which is available for palynologists on request. •Fully automatic precise approach for pollen images detection and classification for bright-field microscopy.•The largest open pollen dataset from the bright-field microscope annotated for the classification and detection tasks.•A web service for palynologists and researchers based on our methods, available at https://pollen-analyst.ru/on request.

Japanese cedar (JC, Cryptomeria japonica) pollen allergens are the primary cause of JC pollinosis, a widespread seasonal allergic disorder and a significant public health issue in Japan. Nevertheless, rare information on repressing the pollen allergens released from JC pollen is available. This study aims to validate the repression of allergen Cry j 1 (the dominant JC pollen allergen that triggers JC pollinosis) using todomatsu oil produced from Abies sachalinensis waste, through surface plasmon resonance (SPR) experiments, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and blind docking simulation. The findings revealed that todomatsu oil reduces the antibody reactivity and content of allergen Cry j 1 by 85.96% and 42.12%, respectively. The docking modeling suggested that alkyl hydrophobic forces, pi–sigma bonding, and hydrogen bonding are the principal motivating forces for todomatsu oil components to dock with allergen Cry j 1. More than 50% of the amino-acid residues docked by each todomatsu oil component (except α-pinene) are hydrophobic. Furthermore, oil components, especially β-maaliene, exhibited potent repression of allergen Cry j 1. Consequently, todomatsu oil, due to its inexpensive, available, convenient, and ecologically beneficial nature, is a viable measure to repress allergen Cry j 1.

ObjectivesAutoimmune and allergic diseases are outcomes of the dysregulation of the immune system. Our study aimed to elucidate differences or shared components in genetic backgrounds between autoimmune and allergic diseases.MethodsWe estimated genetic correlation and performed multi-trait and cross-population genome-wide association study (GWAS) meta-analysis of six immune-related diseases: rheumatoid arthritis, Graves’ disease, type 1 diabetes for autoimmune diseases and asthma, atopic dermatitis and pollinosis for allergic diseases. By integrating large-scale biobank resources (Biobank Japan and UK biobank), our study included 105 721 cases and 433 663 controls. Newly identified variants were evaluated in 21 778 cases and 712 767 controls for two additional autoimmune diseases: psoriasis and systemic lupus erythematosus. We performed enrichment analyses of cell types and biological pathways to highlight shared and distinct perspectives.ResultsAutoimmune and allergic diseases were not only mutually classified based on genetic backgrounds but also they had multiple positive genetic correlations beyond the classifications. Multi-trait GWAS meta-analysis newly identified six allergic disease-associated loci. We identified four loci shared between the six autoimmune and allergic diseases (rs10803431 at PRDM2, OR=1.07, p=2.3×10−8, rs2053062 at G3BP1, OR=0.90, p=2.9×10−8, rs2210366 at HBS1L, OR=1.07, p=2.5×10−8 in Japanese and rs4529910 at POU2AF1, OR=0.96, p=1.9×10−10 across ancestries). Associations of rs10803431 and rs4529910 were confirmed at the two additional autoimmune diseases. Enrichment analysis demonstrated link to T cells, natural killer cells and various cytokine signals, including innate immune pathways.ConclusionOur multi-trait and cross-population study should elucidate complex pathogenesis shared components across autoimmune and allergic diseases.

Sugi-pollinosis poses a significant socioeconomic and public health concern in Japanese society. Consequently, the use of male-sterile plants (pollen-free plants or PFPs) is anticipated in reforestation efforts. In this context, we developed an improved, simplified method for efficiently propagating sugi PFPs. In the present study, we compared the efficiency of different embryogenic cell lines (ECLs) in producing somatic embryos and examined how effectively these embryos germinate and convert into plantlets. We also evaluated the germination potential of somatic embryos stored for various durations at temperatures above freezing and room temperature. The production efficiency of somatic embryos ranged from 129.6 to 504.1 per plate, with an average of 349.8 across the ECLs tested. The overall average germination and conversion rates of somatic embryos were found to be 93.9% and 92.4%, respectively. Furthermore, although differences were observed among the evaluated genotypes, our five-year study demonstrated that sugi somatic embryos could be stored at 25 °C, 15 °C, or 5 °C for 6, 12, or 24 months, respectively, without a notable decline in germination capacity. The developed method enhances flexibility in plant production scheduling and facilitates the optimal timing for transferring somatic seedlings to the field.

Existing API approaches usually independently leverage detection or classification models to distinguish allergic pollens from Whole Slide Images (WSIs). However, palynologists tend to identify pollen grains in a progressive learning manner instead of the above one-stage straightforward way. They generally focus on two pivotal problems during pollen identification. (1) Localization: where are the pollen grains located? (2) Classification: which categories do these pollen grains belong to? To perfectly mimic the manual observation process of the palynologists, we propose a progressive method integrating pollen localization and classification to achieve allergic pollen identification from WSIs. Specifically, data preprocessing is first used to cut WSIs into specific patches and filter out blank background patches. Subsequently, we present the multi-scale detection model to locate coarse-grained pollen regions (targeting at “pollen localization problem”) and the multi-classifiers combination to determine the fine-grained category of allergic pollens (targeting at “pollen classification problem”). Extensive experimental results have demonstrated the feasibility and effectiveness of our proposed method.

Accumulating evidence suggests that Lactococcus lactis subsp. cremoris YRC3780 isolated from kefir has the potential to alleviate allergic responses. Herein, we investigated the effect of YRC3780 on a murine model of Japanese cedar pollinosis (JCP). BALB/c mice immunized with cedar pollen extract (CPE) exhibited an increase in serum immunoglobulin E and developed nasal inflammatory responses including sneezing, nasal hyperresponsiveness, and nasal eosinophil accumulation upon intranasal allergen challenge. These responses were suppressed by the oral administration of YRC3780, although the effects on CPE-induced sneezing response and eosinophil infiltration were not statistically significant. Total fecal microbiota diversity was not affected by allergen immunization and challenge or by YRC3780 administration. However, the abundances of Bifidobacteriales, Veillonellaceae, Lactococcus, and Lactococcus lactis were larger and that of Bacteroides was smaller in YRC3780-treated mice compared with those in CPE-challenged and YRC3780-untreated mice. Our findings suggest the usefulness of YRC3780 for alleviating JCP.

Sublingual immunotherapy for Japanese cedar pollinosis can improve the symptoms of allergic rhinitis and modify its natural course. However, sublingual immunotherapy requires a long treatment period and some patients do not respond to treatment. In this study, we aimed to identify biomarkers that could predict the efficacy of sublingual immunotherapy at an early stage. In this study, 40 patients from phase III trials were recruited and divided into good and poor response groups. Using peripheral blood mononuclear cells from before and two months after the start of medication, microarray, discriminant analysis, and real-time polymerase chain reaction were performed to extract candidate genes that could be biomarkers. Furthermore, these genes were validated in 30 patients in general clinical practice. Complement factor H was upregulated in the good response group and downregulated in the poor response group. Complement factor H may be a useful biomarker for predicting the efficacy of sublingual immunotherapy for Japanese cedar pollinosis at early time points after treatment initiation.

In allergic models, administration of rice that expresses a hybrid peptide consisting of 7 major T cell epitopes of Cry j 1 and Cry j 2 (7Crp), suppressed allergic symptoms, IgE elevation and specific T cell response to Japanese cedar pollen. To evaluate the efficacy and safety of 7Crp-expressing rice in patients with Japanese cedar pollinosis. A 24-week randomized, double-blind, placebo-controlled study was performed to see the efficacy of 7Crp on allergic symptoms using scoring systems, in which 45 patients were assigned to take either 5 g, 20 g test rice, or placebo daily. A 96-week open study was also conducted to determine its inhibitory effect on serum IgE and T cell proliferative response for Japanese cedar pollen, in which 10 patients consumed 5 g test rice daily. No adverse events associated with the test rice occurred, and the intake rate was more than 96%. The test rice did not show suppression of symptoms related to Japanese cedar pollinosis within 24 weeks. However, intake of 5 g test rice led to a significant decrease in T cell response to Japanese cedar pollen during and after the second disperse season in a 96-week open trial, whereas the specific IgE titer remained unchanged. Tolerability and safety of 7Crp-expressing rice was accepted. Daily intake of up to 20 g transgenic rice did not provide beneficial effects on Japanese cedar pollinosis within 24 weeks, however, continuous intake of 5 g rice might reduce allergen specific T cell response.

Sublingual immunotherapy (SLIT) often has low adherence rates. To provide effective support for SLIT continuation, we investigated potential predictors of SLIT adherence through a prospective analysis of patient characteristics. We excluded evaluation of treatment effect and symptoms during treatment, aiming instead to identify predictors of later dropout or insufficient adherence due to indolence or forgetfulness using only information obtained at initial examination. We provided patients with a questionnaire and monitored self-reported adherence once every 6 months. Cases of dropout for clear reasons were excluded, but cases of dropout or insufficient adherence to SLIT for indolence or forgetfulness were included. Fifty-three patients receiving SLIT were assessed. Nine patients dropped out after providing a clear reason. Thirty-four patients maintained good adherence. Seven patients continued SLIT but with insufficient adherence, while three patients discontinued SLIT for unclear reasons (indolence or forgetfulness) and these ten individuals were classified as the poor-adherence group. Univariate analysis and multivariate logistic regression analysis of the good-adherence and poor-adherence groups showed age to be a significant predictor of SLIT adherence. Based on analysis of a receiver operating characteristic curve, age < 40.5 years was selected as the optimal cutoff value for predicting poor adherence to SLIT. To prevent treatment SLIT discontinuation on account of indolence or forgetfulness, the necessity of longterm treatment continuity should be communicated clearly prior to commencing treatment, especially for patients under 40 years of age.