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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.

Some types of airborne pollen can cause pollinosis, and several studies have been conducted on the fluctuation and prediction of their dispersal amount. In Sapporo, Betula pollen is the main cause of hay fever, as in Europe and North America, and various types of pollen other than Betula pollen are dispersed from early spring to autumn. These pollen grains vary in size and shape, and the distribution of their sources is also diverse. In this study, in order to obtain knowledge about the localized pollen dispersion trends within the same city, airborne pollen was comprehensively observed for six years at two sites, one in the center of Sapporo and the other about 10 km away near the mountain area. In addition, stellate hairs, which are airborne substances derived from plants other than pollen, were also observed. Cryptomeria pollen showed the highest correlation between the two sites among all 17 pollen groups. Betula pollen includes three species ( B. platyphylla , B. maximowicziana and B. ermanii ) that differ in dispersal time, size and distribution of source plants, but it showed a high correlation between the two sites. Although it was revealed that the trends differed depending on the pollen, it is interesting that large pine pollen with air sacs showed high correlation only in the daily fluctuations. We believe that it is useful information that a statistically high correlation was shown between the two locations in both daily and annual fluctuations of Cryptomeria and Betula pollens, which are involved in pollinosis in Japan.

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.

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.

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.

Allergic rhinitis (AR) is a common inflammatory condition of the nasal mucosa and it is an immunoglobulin E–mediated disease. The incidence and prevalence of AR globally have been escalating over recent years. Antihistamines, intranasal corticosteroids, decongestants, intranasal anticholinergics, intranasal cromolyn, leukotriene receptor antagonists and immunotherapy have been used in the treatment of AR. However, there is a need to search for more effective and safer remedies as many of the current treatments have reported side effects. Medicinal plants have been used traditionally to relief symptoms of AR but their efficacy and safety have not been scientifically proven. In this review, up-to-date reports of studies on the anti-allergic rhinitis of several medicinal plants and their bioactive metabolites through suppression of the immune system are compiled and critically analyzed. The plant samples were reported to suppress the productions of immunoglobulin E, cytokines and eosinophils and inhibit histamine release. The suppression of cytokines production was found to be the main mechanistic effect of the plants to give symptomatic relief. The prospect of these medicinal plants as sources of lead molecules for development of therapeutic agents to treat AR is highlighted. Several bioactive metabolites of the plants including shikonin, okicamelliaside, warifteine, methylwarifteine, luteolin-7- O -rutinoside, tussilagone, petasin, and mangiferin have been identified as potential candidates for development into anti-allergic rhinitis agents. The data collection was mainly from English language articles published in journals, or studies from EBSCOHOST, Medline and Ovid, Scopus, Springer, and Google Scholar databases from the year 1985–2020. The terms or keywords used to find relevant studies were allergic rhinitis OR pollinosis OR hay fever, AND medicinal plant OR single plant OR single herb OR phytotherapy. This comprehensive review serves as a useful resource for medicinal plants with anti-allergic rhinitis potential, understanding the underlying mechanisms of action and for future exploration to find natural product candidates in the development of novel anti-allergic rhinitis agents.

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.