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Background Periostin, a matricellular protein that modulates cell functions having various pathophysiological roles, has the potential to be a useful biomarker for various diseases. We recently found that periostin forms a complex with IgA in human serum, which may affect the periostin measurement. Methods We investigated (1) whether the formation of the periostin-IgA complex affects the original periostin ELISA system, decreasing the values of serum periostin? (2) bow each domain of periostin affects periostin measurement by the original periostin ELISA system? (3) whether we can establish a novel ELISA system that is not affected by formation of the IgA complex? Results The periostin value at the reducing condition was significantly higher than that of the non-reducing condition, demonstrating that formation of the IgA complex affects periostin measurement. The monoclonal antibodies (mAbs) for periostin recognizing the EMI and R1 domains immunoprecipitated serum periostin in the reducing condition more than in the non-reducing condition, whereas the mAbs recognizing the R2 or R3 domain immunoprecipitated comparable amounts of serum periostin in the reducing and non-reducing conditions, suggesting the EMI and R1 domains contribute to formation of the complex with IgA. Using SS16A recognizing the R3 domain combined with SS17B recognizing the R4 domain, we established an ELISA system that was able to measure periostin independently of the IgA complex. Conclusions We have established a novel ELISA system that measures periostin independently of the IgA complex. This system is promising in identifying periostin as a biomarker for various diseases.

Background: The chitinase-like protein YKL-40 is associated with airflow limitation on spirometry and airway remodeling in patients with asthma. It remains unclear whether YKL-40 is associated with morphologic changes in the airways and parenchyma or with future progression of airflow limitation in severe asthma. Objective: To evaluate the association of circulating YKL-40 levels with morphologic changes in the airways and parenchyma and with longitudinal progression of airflow limitation. Methods: The patients were participants in the Hokkaido Severe Asthma Cohort Study (n = 127), including smokers. This study consisted of 2 parts. In analysis 1, we analyzed associations between circulating YKL-40 levels and several asthma-related indices, including computed tomography-derived indices of proximal wall area percentage, the complexity of the airways (airway fractal dimension), and the parenchyma (exponent D) crosssectionally (n = 97). In analysis 2, we evaluated the impact of circulating YKL-40 levels on forced expiratory volume in 1 second (FEV1) decline longitudinally for a 5-year follow-up (n = 103). Results: Circulating YKL-40 levels were significantly associated with proximal wall area percentage and airway fractal dimension (r = 0.25, P = .01; r = -0.22, P = .04, respectively), but not with exponent D. The mean annual change in FEV1 was -33.7 (+/- 23.3) mL/y, and the circulating YKL-40 level was a significant independent factor associated with annual FEV1 decline (beta = -0.24, P =.02), even after controlling for exponent D (beta = -0.26, P = .01). Conclusion: These results provide further evidence for the association of YKL-40 with the pathogenesis of airway remodeling in severe asthma. (C) 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Long-term voice abuse or sudden vocal fold microvascular disruption may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and also in various otolaryngological diseases. The aim of this article was to investigate the expression and the role of periostin in the formation of vocal fold polyps. The expression patterns of periostin in 59 surgical specimens of vocal fold polyps from 54 patients were investigated immunohistochemically. Normal vocal fold mucosa specimens from 5 patients who had undergone total laryngectomy were used as the control group. Retrospective study with planned data collection was conducted at Tohoku Medical and Pharmaceutical University. Expression of periostin was detected in 43 (72.9%) samples and four patterns of periostin expression were observed in vocal fold polyps: negative type, superficial type, infiltrative type, and diffuse type. An association was observed between periostin expression patterns and the histological subtypes of vocal fold polyps. The infiltrative pattern of periostin expression was significantly dominant in vascular-hyaline types. Expression of transforming growth factor-β (TGF-β) was also detected in the vocal fold polyps. Our results confirmed that periostin might be involved in certain pathological changes in vocal fold polyps, such as extracellular matrix accumulation, local fibrosis, and formation and development of vocal fold polyps.

Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth and affects long-term respiratory outcomes. The objectives of this study were to establish whether serum periostin at birth, day of life (DOL) 28, and corrected 36 weeks' gestational age could be potential biomarkers for BPD.A total of 98 preterm Japanese infants born at 32 weeks and comparing 41 healthy controls born at term, were divided into BPD (n = 44) and non-BPD (n = 54) cohorts. Serum periostin levels were measured using an enzyme-linked immunosorbent assay.Among 98 preterm infants, the median serum periostin levels at birth were higher with BPD (338.0 ng/mL) than without (275.0 ng/mL, P 0.001). Multivariate analysis revealed that serum periostin levels at birth were significantly associated with BPD (P = 0.013). Serum periostin levels at birth with moderate/severe BPD (345.0 ng/mL) were significantly higher than those with non-BPD/mild BPD (283.0 ng/mL, P = 0.006).Serum periostin levels were significantly correlated with birth weight and gestational age, and serum periostin levels at birth in BPD infants were significantly higher than that in non-BPD infants.This study found higher serum periostin levels at birth in preterm infants subsequently diagnosed with bronchopulmonary dysplasia. It also emerged that serum periostin levels at birth significantly correlated with gestational age and birth weight. The mechanism by which serum periostin is upregulated in BPD infants needs further investigation.

Purpose: To elucidate the usefulness of Japanese cedar pollen (JCP)-specific antigen-specific immunoglobulin (IgG) 4 as a biomarker for predicting the efficacy of sublingual immunotherapy for cedar pollen-induced allergic rhinitis. Methods: We divided a total of 105 cases with Japanese cedar pollinosis into three groups: “SLIT Successful,” SLIT Unsatisfactory,” and “SCIT” groups. The SLIT group patients were treated with JCP Droplet (Torii Pharmaceutical Co. Ltd., Tokyo, Japan) for one year from 2015 and were divided into two groups, the SLIT Successful group or the SLIT Unsatisfactory group. The SLIT Successful group (n = 16) were subjects treated by SLIT only, who were able to experience control of their naso-ocular symptoms without the need for antiallergic rescue agents during the peak season of atmospheric pollen. The SLIT Unsatisfactory group (n = 76) comprised subjects treated with SLIT only, who did not respond successfully, and were administered with rescue agents to control their naso-ocular symptoms. The SCIT group had been treated with standardized JCP extract (Torii Pharmaceutical Co., Ltd., Tokyo, Japan) for three years from 2012, and were also able to experience control of their symptoms during the peak pollen season without the need for antiallergic rescue agents. We determined the serum level of JCP-specific immunoglobulin E (IgE), IgG, and IgG4 used in the 3gAllergy-specific IgE assay (3gAllergy). The serum levels of periostin and SCCA2 were measured using established ELISA procedures (clones SS18A and SS17B, Shino-Test, Japan) following the manufacturer’s instructions. We then made ROC curves for each group and assessed which index was best able to predict the efficacy of sublingual immunotherapy. Results: Serum JCP-specific IgE was significantly lower in the SCIT group than in the SLIT Successful group and the SLIT Unsatisfactory group (p &lt, 0.05). Serum JCP-specific IgG was significantly higher in the SCIT group and the SLIT Successful group than in the SLIT Unsatisfactory group (p &lt, 0.05). Serum JCP-specific IgG4 was also significantly higher in the SCIT group and the SLIT Successful group than in the SLIT Unsatisfactory group (p &lt, 0.05). There was no significant difference among serum levels of periostin in the SCIT group, the SLIT Successful group, or the SLIT Unsatisfactory group. There was also no significant difference in SCCA2 among the three groups. In terms of ROC curves, a serum JCP-specific IgG4 value greater than 989.5 UA/mL showed the best sensitivity (93.3%) and specificity (94.7%) (p &lt, 0.05) among other parameters. Conclusions: The serum JCP-specific IgG4 level is significantly correlated with the clinical efficacy of SLIT. Serum JCP-specific IgG4 cutoff levels greater than 989.5 UA/mL were correlated with an effective clinical response to SLIT, with a sensitivity of 93.3% and a specificity of 94.7%.

Systemic sclerosis (SSc) is a chronic, heterogenous disease of connective tissue characterized by organ fibrosis together with vascular injury and autoimmunity. Transforming growth factor (TGF)-β plays a central role in generating fibrosis, including SSc. Periostin is a matricellular protein playing a key role in the generation of fibrosis by amplifying the TGF-β signals. SOX (SRY-related HMG box) 11 is a transcription factor playing several important roles in organ development in embryos. We have previously shown that SOX11 induces periostin expression. However, the roles of the interactions among the TGF-β signals, periostin, and SOX11 remain unknown in the pathogenesis of SSc. In this study, we found that most clones of dermal fibroblasts derived from SSc patients showed constitutive, high expression of SOX11, which is significantly induced by TGF-β1. SOX11 forms a positive loop with periostin to activate the TGF-β signals in SSc dermal fibroblasts. Genetic deletion of Sox11 in Postn-expressing fibroblasts impairs dermal fibrosis by bleomycin. Moreover, using the DNA microarray method, we identified several fibrotic factors dependent on the TGF-β/SOX11/periostin pathway in SSc dermal fibroblasts. Our findings, taken together, show that a positive loop formed by SOX11 and periostin in fibroblasts upregulates the TGF-β signals, leading to skin fibrosis.

Atopic dermatitis (AD) is a chronic relapsing skin disease accompanied by recurrent itching. Although type 2 inflammation is dominant in allergic skin inflammation, it is not fully understood how non-type 2 inflammation co-exists with type 2 inflammation or how type 2 inflammation causes itching. We have recently established the FADS mouse, a mouse model of AD. In FADS mice, either genetic disruption or pharmacological inhibition of periostin, a downstream molecule of type 2 inflammation, inhibits NF-κB activation in keratinocytes, leading to downregulating eczema, epidermal hyperplasia, and infiltration of neutrophils, without regulating the enhanced type 2 inflammation. Moreover, inhibition of periostin blocks spontaneous firing of superficial dorsal horn neurons followed by a decrease in scratching behaviors due to itching. Taken together, periostin links NF-κB-mediated inflammation with type 2 inflammation and promotes itching in allergic skin inflammation, suggesting that periostin is a promising therapeutic target for AD.

An expert workshop in collaboration of the German Society of Allergy and Clinical Immunology (DGAKI) and the Japanese Society of Allergy (JSA) provided a platform for key opinion leaders of both countries aimed to join expertise and to highlight current developments and achievements in allergy research. Key domains of the meeting included the following seven main sections and related subchapters: 1) basic immunology, 2) bronchial asthma, 3) prevention of allergic diseases, 4) food allergy and anaphylaxis, 5) atopic dermatitis, 6) venom allergy, and 7) upper airway diseases. This report provides a summary of panel discussions of all seven domains and highlights unmet needs and project possibilities of enhanced collaborations of scientific projects. © Dustri-Verlag Dr. K. Feistle.

Fractional exhaled nitric oxide (FeNO) may have a role both as a prognostic and predictive biomarker, in combination with eosinophils, for assessing responsiveness to some biological therapies.We evaluated the value of baseline FeNO, adjusted for baseline blood eosinophil levels and other clinical characteristics, as an independent predictor of treatment response to dupilumab in patients with uncontrolled, moderate-to-severe asthma.We performed a post-hoc analysis of LIBERTY ASTHMA QUEST (NCT02414854), a phase 3, double-blind study in patients aged ≥ 12 years with uncontrolled moderate-to-severe asthma who received dupilumab 200/300 mg, or placebo every 2 weeks up to 52 weeks. Annualized event rate (AER) of severe exacerbations and least squares mean change from baseline in pre-bronchodilator forced expiratory volume in 1 s (FEVAER increased with increasing baseline FeNO in placebo, and decreased in dupilumab groups. The relative risk of severe exacerbations was 22·7%, 58·3%, and 69·3% lower for dupilumab vs placebo for the FeNO25, 25 to50, and ≥ 50 ppb subgroups. The magnitude of FEVIncreased baseline FeNO was associated with greater clinical effects in dupilumab vs placebo, independent of eosinophil levels and other clinical characteristics.

Background Some patients with sarcoidosis experience worsening of pulmonary lesions. However, no biomarker has been identified that reflects pulmonary disease status in sarcoidosis. We investigated the usefulness of potential markers of pulmonary fibrosis in patients with sarcoidosis. Methods Plasma matrix metalloproteinase 7 (MMP-7), CC-chemokine ligand 18 (CCL-18), and periostin levels were evaluated in 60 patients with sarcoidosis and 30 healthy controls; bronchoalveolar lavage fluid levels were analyzed in 22 patients with sarcoidosis. To determine the usefulness of these markers, we explored potential correlations between these markers and sarcoidosis clinical characteristics. Results Plasma MMP-7, CCL-18, and periostin concentrations were significantly higher in patients with sarcoidosis than those in healthy controls. MMP-7 concentrations in plasma and bronchoalveolar lavage fluid were higher in patients with sarcoidosis with parenchymal infiltration than in those without lung lesions. Moreover, MMP-7 concentration was negatively correlated with pulmonary function. Conclusion Among these novel biomarkers, MMP-7 most precisely reflected pulmonary sarcoidosis disease status and thus, might be useful for diagnosing and evaluating sarcoidosis, particularly in patients with pulmonary parenchymal lesions.

Interleukin (IL)-24 is a member of the IL-20 family of cytokines and is produced by various types of cells, such as CD4+ T cells, NK cells, mast cells, keratinocytes, bronchial epithelial cells, and myofibroblasts. Previous studies suggest that IL-24 plays an essential role in the pathogenesis of pro-inflammatory autoimmune disorders such as psoriasis, arthritis, and inflammatory bowel diseases. However, the role of IL-24 in the pathogenesis of allergic diseases has been elusive. It has already been reported that IL-24 is involved in the pathogenesis of allergic lung and skin diseases. Moreover, we have recently revealed for the first time the pivotal functions of IL-24 in IL-13–mediated skin barrier dysfunction in atopic dermatitis (AD), which is known to be a characteristic of AD caused by Th2 cytokines such as IL-4 or IL-13. In this review, we show recent advances in the basic characteristics of IL-24 and its novel functions in the pathogenesis of allergic skin inflammation, focusing on AD. A better understanding of the role of IL-24 in allergic diseases can lead to the development of new therapeutic options.

Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic ...

Omalizumab is more effective in severe allergic patients with eosinophilic asthma than those with non-eosinophilic asthma. IL-18, a unique cytokine involved in allergic but non-eosinophilic inflammation, might be associated with the latter condition. We aimed to clarify the roles of IL-18 related pathways in insufficient response to omalizumab treatment.Patients with severe allergic asthma who completed 2-year omalizumab treatments at Kyoto University Hospital were included in this study (UMIN000002389). Associations between pretreatment levels of serum free IL-18 in addition to other mediators and asthma phenotypes including responses to omalizumab treatment were analyzed. Changes in serum free IL-18, periostin and total IgE levels during the treatment were also examined.Twenty-seven patients (19 females, average age of 55.7 years) were examined. Fifteen incomplete responders who experienced exacerbations in the second year, were significantly and more frequently obese and showed significantly earlier asthma onset, lower blood eosinophils and more exacerbations before omalizumab treatment than complete responders. Significantly more patients showed high baseline serum free IL-18 levels (≥141 pg/mL, a threshold for the highest tertile) among the incomplete responders than complete responders. Patients with high serum free IL-18 levels shared similar characteristics with incomplete responders, showing significant reductions in serum total IgE levels during omalizumab treatment. Finally, serum free IL-18 levels negatively correlated with serum periostin levels at baseline and in change ratios.High baseline serum free IL-18 levels may predict reduced omalizumab efficacy in severe allergic patients with type-2 low asthma, regarding reduction of exacerbations.

Interleukin (IL)-4 and IL-13, signature type 2 cytokines, exert their actions by binding to two types of receptors sharing the IL-4R α chain (IL-4Rα). Since IL-4 and IL-13 play important and redundant roles in the pathogenesis of allergic diseases, blocking both the IL-4 and IL-13 signals would be a powerful and effective strategy for treating allergic diseases. Dupilumab (Dupixent®) is a fully human monoclonal antibody recognizing IL-4Rα and blocking both the IL-4 and IL-13 signals. Dupilumab was first prescribed for atopic dermatitis (AD) patients and has been widely approved for adult patients with moderate to severe AD since 2018. Dupilumab has since been used for asthma, receiving approval for uncontrolled asthma in 2019. A phase 3 study using dupilumab for chronic rhinosinusitis with nasal polyps (CRSwNP) has been just completed, with positive results. Several clinical trials of dupilumab for other diseases in which type 2 inflammation is dominant are now underway. It is hoped that dupilumab will open the door to a new era for treating allergic patients with AD, asthma, and CRSwNP, and for more patients with type 2 inflammations. Keywords: Asthma, Atopic dermatitis, Chronic rhinosinusitis with nasal polyps, Interleukin-4, Interleukin-13

Introduction Dynamic hyperinflation (DH) is sometimes observed and is associated with impaired daily life activities of asthma. We assessed the relationship between DH and asthma biomarkers (blood eosinophil, fractional exhaled nitric oxide (FeNO) and serum periostin) in patients with asthma. Methods Fifty patients with stable asthma were prospectively recruited and underwent blood test, FeNO measurement, spirometry and metronome-paced tachypnoea (MPT) test to assess DH. In MPT tests, inspiratory capacity (IC) was measured at baseline and after 30 s of MPT with breathing frequencies of 20, 30 and 40 breaths·min−1. DH was assessed by the decline of IC from baseline, and maximal IC reduction ≥10% was considered as positive DH. Results Thirty patients (60%) showed positive DH. Patients with positive DH showed higher serum periostin levels (107.0±30.7 ng·mL−1) than patients with negative DH (89.7±23.7) (p=0.04). Patients in Global Initiative for Asthma treatment steps 4–5 (n=19) showed higher serum periostin levels (p=0.01) and more severe IC reduction after MPT (p, Serum periostin level as a marker of dynamic hyperinflation in patients with asthma https://bit.ly/3djKTeQ