Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and ...reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today.
To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.
Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and ...reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today.
To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.
Th2 Cells in Health and Disease Nakayama, Toshinori; Hirahara, Kiyoshi; Onodera, Atsushi ...
Annual review of immunology,
04/2017, Letnik:
35, Številka:
1
Journal Article
Recenzirano
Helper T (Th) cell subsets direct immune responses by producing signature cytokines. Th2 cells produce IL-4, IL-5, and IL-13, which are important in humoral immunity and protection from helminth ...infection and are central to the pathogenesis of many allergic inflammatory diseases. Molecular analysis of Th2 cell differentiation and maintenance of function has led to recent discoveries that have refined our understanding of Th2 cell biology. Epigenetic regulation of
Gata3
expression by chromatin remodeling complexes such as Polycomb and Trithorax is crucial for maintaining Th2 cell identity. In the context of allergic diseases, memory-type pathogenic Th2 cells have been identified in both mice and humans. To better understand these disease-driving cell populations, we have developed a model called the pathogenic Th population disease induction model. The concept of defined subsets of pathogenic Th cells may spur new, effective strategies for treating intractable chronic inflammatory disorders.
For patients with head and neck squamous cell carcinoma (HNSCC), survival rates have not improved due to local recurrence and distant metastasis. Current targeted molecular therapies do not ...substantially benefit HNSCC patients. Therefore, it is necessary to use advanced genomic approaches to elucidate the molecular mechanisms underlying the aggressiveness of HNSCC cells. Analysis of our microRNA (miRNA) expression signature by RNA sequencing showed that the miR‐199 family (miR‐199a‐5p, miR‐199a‐3p, miR‐199b‐5p and miR‐199b‐3p) was significantly reduced in cancer tissues. Ectopic expression of mature miRNA demonstrated that all members of the miR‐199 family inhibited cancer cell migration and invasion by HNSCC cell lines (SAS and HSC3). These findings suggested that both passenger strands and guide strands of miRNA are involved in cancer pathogenesis. In silico database and genome‐wide gene expression analyses revealed that the gene coding for integrin α3 (ITGA3) was regulated by all members of the miR‐199 family in HNSCC cells. Knockdown of ITGA3 significantly inhibited cancer cell migration and invasion by HNSCC cells. Moreover, overexpression of ITGA3 was confirmed in HNSCC specimens, and high expression of ITGA3 predicted poorer survival of the patients (P = 0.0048). Our data revealed that both strands of pre‐miR‐199a (miR‐199a‐5p and miR‐199a‐3p) and pre‐miR‐199b (miR‐199b‐5p and miR‐199b‐3p) acted as anti‐tumor miRNA in HNSCC cells. Importantly, the involvement of passenger strand miRNA in the regulation of cellular processes is a novel concept in RNA research. Novel miRNA‐based approaches for HNSCC can be used to identify potential targets for the development of new therapeutic strategies.
Expression of all members of the miR‐199 family was significantly reduced in HNSCC specimens and ectopic expression of miR‐199 family significantly suppressed cancer cell migration and invasion. The integrin a3 gene (ITGA3) was directly regulated by all members of the miR‐199 family in HNSCC cells. Overexpression of ITGA3 was detected in HNSCC clinical specimens, and high expression of ITGA3 predicted shorter survival in patients with HNSCC.
We conducted a randomized, placebo-controlled, double-blind clinical trial to investigate the optimal dose and long-term efficacy and safety of Japanese cedar (JC) pollen tablets for SLIT ...(JapicCTI-142579). Here, we report details of the effects of the JC pollen SLIT tablet on rhinitis and conjunctivitis symptoms over three pollen dispersal seasons.
A total of 1042 JC pollinosis patients (aged 5–64 years) were randomized to receive tablets containing placebo (P), 2000, 5000, or 10,000 Japanese allergy units (JAU) of JC pollen for 15 months to identify an optimal dose. Patients receiving P (n = 240) and the optimal dose (5000 JAU; A, n = 236) were then randomized to receive P or A for an additional 18 months (AA, AP, PA, and PP groups, allocation ratio 2:1:1:2). Nasal and ocular symptoms, rescue medication use, and quality of life (QOL) were assessed on quantitative scales.
In the second and third seasons, the AA, AP, and PA groups exhibited significantly better improvements in nasal, ocular, and medication scores compared with the PP group in the order AA > AP > PA > PP during the second season and AA > PA > AP > PP during the third season. Rescue medication use and QOL scores were also significantly better in the AA, AP, and PA groups compared with the PP group.
The JC pollen SLIT tablet relieved nasal and ocular symptoms and medication use and improved QOL in a treatment duration-dependent manner. Continuous dosing regimens appear to enhance the efficacy of the drug.
The Japanese cedar pollen SLIT tablets exhibited treatment duration-dependent efficacy. Display omitted
The introduction of immune checkpoint inhibitors in cancer treatment highlights the negative regulation of anti-tumor immunity, such as effector T-cell exhaustion in the tumor microenvironment. ...However, the mechanisms underlying the induction and prevention of T-cell exhaustion remain largely unknown. We found that CD69, a type II glycoprotein known to regulate inflammation through T-cell migration and retention in tissues, plays an important role in inducing the exhaustion of tumor-infiltrating T cells. Cd69-/- mice showed reduced tumor growth and metastasis in a 4T1-luc2 murine breast cancer model, in which increased numbers of tumor-infiltrating lymphocytes, relatively little T-cell exhaustion, and enhanced IFNγ production were observed. Anti-CD69 monoclonal antibody treatment attenuated the T-cell exhaustion and tumor progression in tumor-bearing mice. These findings highlight a novel role of CD69 in controlling the tumor immune escape mediated by T-cell exhaustion and indicate that CD69 is a novel target for cancer immunotherapy.
Background
The efficacy and safety of 300 index of reactivity (IR) tablets of house dust mite (HDM) allergen extracts in Japanese pediatric (5‐16 years old) patients with allergic rhinitis (AR) were ...assessed in a double‐blind, randomized, placebo‐controlled study (JAPIC CTI‐152981).
Methods
Patients were randomized 1:1 to HDM sublingual tablets or placebo once daily for 52 weeks. The primary end‐point was average adjusted symptom score (AASS; average of daily Rhinitis Total Symptom Scores, comprising sneezing, rhinorrhea, nasal congestion, and nasal pruritus, adjusted for rescue medication use), analyzed during Weeks 48‐52 (mixed‐effects model for repeated measures).
Results
Of 438 patients randomized, 403 (92%; 193 active, 210 placebo) completed the study. AASS (least‐squares LS mean SE) during Weeks 48‐52 was significantly (P = 0.0005) lower in the active group compared with placebo (6.32 0.20 vs 7.27 0.19; relative LS mean difference, −13%). Immunological responses (IgE and IgG4 antibodies specific to antigens of two HDM species) were significantly greater in the active group compared with placebo (P < 0.0001). Almost all patients experienced mild or moderate adverse events (AEs). The most common treatment‐related AEs were oral pruritus, mouth edema, throat irritation, and ear pruritus. One patient experienced serious pseudocroup (subglottic laryngitis) that recovered. There were no deaths or anaphylaxis requiring the use of injectable adrenaline.
Conclusions
The HDM tablet significantly improved symptoms of HDM‐induced perennial AR and was associated with a significant immunological response. The safety profile in pediatric patients was consistent with that in adults, with no new safety concerns.
Background
The SQ house dust mite (HDM) sublingual immunotherapy (SLIT)‐tablet (TO‐203, Torii, Japan/ALK, Denmark) treatment has been effective against respiratory allergic diseases in patients aged ...≥12 years during European, Japanese, and North American trials. This trial was conducted to investigate the efficacy and safety of this treatment in Japanese children (5‐17 years) with moderate‐to‐severe HDM allergic rhinitis (AR).
Methods
In this randomized, double‐blind, placebo‐controlled trial, 458 Japanese children were randomly assigned to a daily SQ HDM SLIT‐tablet 10 000 Japanese Allergy Unit (JAU), equivalent to 6 SQ‐HDM in Europe and the US or placebo (1:1) treatment for 1 year. Inclusion required an AR symptom score of ≥7 on at least 7 days during a 14‐day run‐in period while symptomatic treatment was withdrawn. The primary endpoint was the total combined rhinitis score (TCRS) comprising AR symptom and medication scores during the last 8 weeks of the treatment period.
Results
The analysis of primary endpoint demonstrated statistically significant absolute reduction in TCRS of 1.22 with a relative difference of 23% (95% confidence interval, 14% to 31%) in the 10 000 JAU compared with placebo. Predefined stratified analyses revealed the same degree of efficacy of 1.11 (P = 0.002), 21% (8% to 32%) and 1.36 (P = 0.001), 26% (11% to 38%), respectively, in pediatric (5‐11 years) and adolescent subjects (12‐17 years). The treatment was well tolerated by both pediatric and adolescent subjects.
Conclusion
This trial, for the first time, demonstrated the efficacy and safety of the HDM SLIT‐tablet in pediatric patients with moderate‐to‐severe HDM AR (JapicCTI‐152953).
This randomized, double‐blind, placebo‐controlled phase III clinical trial demonstrated the efficacy and favorable safety profile of the SQ HDM SLIT‐tablet in Japanese pediatric and adolescent patients with moderate‐to‐severe HDM‐induced AR. The 10 000 JAU group showed statistically significant improvement compared with placebo group in primary endpoint, TCRS during the last 8 weeks of the treatment period. No relevant difference in the efficacy and safety profile was observed between pediatric and adolescent subjects. HDM, house dust mite; SLIT, sublingual immunotherapy; AR, allergic rhinitis; JAU, Japanese allergy unit; TCRS, total combined rhinitis score.
Dear Editor, In Japan, allergic rhinitis is one of the most prevalent allergic diseases, and there has been an increase in seasonal allergic rhinitis in recent years. Matsubara et al. reported that ...the overall prevalence of allergic rhinitis was 49.2%, with a marked increase in Japanese cedar (JC) pollinosis among teenagers. Over the past 20 years, the prevalence of JC pollinosis increased from 16.2% in 1998 to 26.5% in 2008 and 38.8% in 2019, and that of non-JC pollinosis also increased from 10.9% to 15.4% and 25.1%, respectively. It is assumed that this may reflect an increase in Japanese cypress (JCY) pollinosis, in addition to increases in grass pollinosis and Asteraceae pollinosis. JC pollinosis is a typical type I allergic disease in which nasal, ocular, pharyngeal, and skin symptoms occur during the JC pollen dispersal season. JC pollinosis significantly affects daily activity, work productivity, learning, sleep, and quality of life. Furthermore, approximately 70% of patients with JC pollinosis are also allergic to JCY pollen.
Early identification of infants at high risk of allergies can improve the efficacy of preventive interventions. However, an established quantifiable risk assessment method in the early postnatal ...period does not exist. TARC (or CCL17) is a Th2 chemokine used as an activity marker for atopic dermatitis (AD). Therefore, we evaluated the association between cord blood TARC (cTARC) and the development of allergic diseases in childhood.
This is a high-risk birth cohort for allergy, consisting of children with a family history of allergy. We collected 263 pairs of maternal and child cord blood samples perinatally and child blood samples at ages 1, 2, and 5 years. TARC and allergen-specific immunoglobulin E levels were measured, and the relationship between allergic diseases was analyzed.
The median cTARC was 989 pg/mL (interquartile range IQR: 667–1430 pg/mL). The cTARC levels in children who developed AD were higher than those in children who did not develop AD, and the association strengthened with younger age (median IQR at 1 year: 1285 816–1965 vs. 933 662–1330 pg/mL, p < 0.01; at 2 years: 1114 787–1753 vs. 950 660–1373 pg/mL, p = 0.02). In the multivariate analysis, cTARC was associated with AD, egg white sensitization, food allergy, allergic rhinitis, and Japanese cedar pollen sensitization.
cTARC was associated with the development of allergic diseases and allergen sensitization in early childhood. These results suggest that, infantile AD-mediated atopic march starts during fetal life, and this immune status is reflected in the cTARC at birth.
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