Biomolecules

Research

10 pages, 986 KiB

Open AccessCommunication

Dupilumab Leads to Clinical Improvements including the Acquisition of Tolerance to Causative Foods in Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Disorders

by Naoya Arakawa, Hisako Yagi, Mariko Shimizu, Daisuke Shigeta, Akihiko Shimizu, Shigeru Nomura, Takumi Takizawa and Yoshiyuki Yamada

Biomolecules 2023, 13(1), 112; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13010112 - 5 Jan 2023

Cited by 4 | Viewed by 2900

Abstract

A recent report showed that most pediatric cases of non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal disorders (EGIDs) (non-EoE EGIDs) are persistent and severe compared with those of EoE, thus requiring further effective therapeutic approaches. In this study, we present the first case based on [...] Read more.

A recent report showed that most pediatric cases of non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal disorders (EGIDs) (non-EoE EGIDs) are persistent and severe compared with those of EoE, thus requiring further effective therapeutic approaches. In this study, we present the first case based on a systematic search of non-EoE EGID for which tolerance to causative foods and histological and symptomatic improvements were achieved following dupilumab administration, after elimination diets and omalizumab and mepolizumab treatments. Driven by this case, we investigated the efficacies of biological treatments in non-EoE EGID cases based on the patient studied herein, and other patients identified in the conducted systematic review. Seven articles, including five different biologics, were reviewed. Both clinical efficacies and impact differences among the targeted molecules are demonstrated in this study. Our findings show that dupilumab may affect mechanisms that can suppress symptoms induced by offending foods that are different from those induced by other biologics as identified in the conducted systematic review. Additional studies are required to address the unmet needs of non-EoE EGID treatments. Full article

(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2021”)

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7 pages, 1378 KiB

Open AccessCommunication

Th17-Dependent Nasal Hyperresponsiveness Is Mitigated by Steroid Treatment

by Shusaku Ueda, Kento Miura, Hideki Kawasaki, Sawako Ogata, Norimasa Yamasaki, Shuka Miura, Akio Mori and Osamu Kaminuma

Biomolecules 2022, 12(5), 674; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12050674 - 6 May 2022

Cited by 2 | Viewed by 1810

Abstract

Th17 cells are implicated in allergic inflammatory diseases, including allergic rhinitis (AR), though the effect of steroids on Th17 cell-dependent nasal responses is unclear. Herein, we investigated a nasal inflammation model elicited by allergen provocation in mice infused with Th17 cells and its [...] Read more.

Th17 cells are implicated in allergic inflammatory diseases, including allergic rhinitis (AR), though the effect of steroids on Th17 cell-dependent nasal responses is unclear. Herein, we investigated a nasal inflammation model elicited by allergen provocation in mice infused with Th17 cells and its responsiveness against steroid treatment. We transferred BALB/c mice with Th17 cells, which were differentiated in vitro and showed a specific reaction to ovalbumin (OVA). We challenged the transferred mice by intranasal injection of OVA and to some of them, administered dexamethasone (Dex) subcutaneously in advance. Then, we assessed immediate nasal response (INR), nasal hyperresponsiveness (NHR), and inflammatory cell infiltration into the nasal mucosa. The significant nasal inflammatory responses with massive neutrophil accumulation, INR, and NHR were induced upon allergen challenge. Allergen-induced INR and NHR were significantly suppressed by Dex treatment. This study suggested the effectiveness of steroids on Th17 cell-mediated nasal responses in AR. Full article

(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2021”)

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6 pages, 995 KiB

Open AccessCommunication

Sequential Biotherapy Targeting IL-5 and IL-4/13 in Patients with Eosinophilic Asthma with Sinusitis and Otitis Media

by Ayumi Chikumoto, Keiji Oishi, Kazuki Hamada, Tsunahiko Hirano, Tomoyuki Kakugawa, Keiko Kanesada and Kazuto Matsunaga

Biomolecules 2022, 12(4), 522; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12040522 - 30 Mar 2022

Cited by 5 | Viewed by 2332

Abstract

Type 2 (T2) inflammation plays an important role in the pathogenesis of allergic diseases such as asthma, eosinophilic chronic rhinosinusitis (ECRS), or eosinophilic otitis media (EOM). Currently, in severe asthma with the T2 phenotype, biologics targeting mediators of T2 inflammation dramatically improve the [...] Read more.

Type 2 (T2) inflammation plays an important role in the pathogenesis of allergic diseases such as asthma, eosinophilic chronic rhinosinusitis (ECRS), or eosinophilic otitis media (EOM). Currently, in severe asthma with the T2 phenotype, biologics targeting mediators of T2 inflammation dramatically improve the management of severe asthma. While treatment with a single biologic is common, little is known about cases of the sequential use of two biologics. Here, we report a case of severe asthma with refractory ECRS and EOM in which total control of these allergic diseases could not be achieved with a single biologic but could be achieved via the sequential use of the anti-IL-5 receptor antibody and human anti-IL-4/13 receptor monoclonal antibody. It is suggested that it is necessary to control multiple T2 inflammatory pathways to achieve total control of severe allergic diseases. Sequential biotherapy may help solve the clinical challenges associated with single-agent molecular-targeted therapies. Full article

(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2021”)

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16 pages, 1621 KiB

Open AccessArticle

Effect of Japanese Cedar Pollen Sublingual Immunotherapy on Asthma Patients with Seasonal Allergic Rhinitis Caused by Japanese Cedar Pollen

by Shoko Ueda, Jun Ito, Norihiro Harada, Sonoko Harada, Hitoshi Sasano, Yuuki Sandhu, Yuki Tanabe, Sumiko Abe, Satomi Shiota, Yuzo Kodama, Tetsutaro Nagaoka, Fumihiko Makino, Asako Chiba, Hisaya Akiba, Ryo Atsuta, Sachiko Miyake and Kazuhisa Takahashi

Biomolecules 2022, 12(4), 518; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12040518 - 29 Mar 2022

Cited by 1 | Viewed by 2369

Abstract

Allergen immunotherapy is a promising treatment for allergic diseases that induce immune tolerance through the administration of specific allergens. In this study, we investigate the efficacy of sublingual immunotherapy (SLIT) in asthmatic patients with SAR-JCP and the dynamics of the parameters before and [...] Read more.

Allergen immunotherapy is a promising treatment for allergic diseases that induce immune tolerance through the administration of specific allergens. In this study, we investigate the efficacy of sublingual immunotherapy (SLIT) in asthmatic patients with SAR-JCP and the dynamics of the parameters before and after treatment in a real-world setting. This was a prospective single-center observational study. Patients with asthma and SAR-JCP (n = 24) were recruited for this study and assessed using symptom questionnaires before SLIT and a year after the SLIT. In addition, a respiratory function test, forced oscillation technique, and blood sampling test were performed during the off-season before and after SLIT. The one-year SLIT for asthma patients with SAR-JCP significantly improved not only allergic rhinitis symptoms, but also asthma symptoms during the JCP dispersal season, and significantly improved airway resistance during the off-season. The change in the asthma control test and the visual analog scale score during the season before and after SLIT was negatively and positively correlated with the change in peripheral blood γδ T cells off-season before and after SLIT, respectively. It was suggested that improvement in asthma symptoms during the JCP dispersal season after SLIT was associated with reduced peripheral blood γδ T cells. Full article

(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2021”)

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Review

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25 pages, 1639 KiB

Open AccessEditor’s ChoiceReview

Immunosenescence, Inflammaging, and Lung Senescence in Asthma in the Elderly

by Tomoyuki Soma and Makoto Nagata

Biomolecules 2022, 12(10), 1456; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12101456 - 11 Oct 2022

Cited by 18 | Viewed by 3413

Abstract

Prevalence of asthma in older adults is growing along with increasing global life expectancy. Due to poor clinical consequences such as high mortality, advancement in understanding the pathophysiology of asthma in older patients has been sought to provide prompt treatment for them. Age-related [...] Read more.

Prevalence of asthma in older adults is growing along with increasing global life expectancy. Due to poor clinical consequences such as high mortality, advancement in understanding the pathophysiology of asthma in older patients has been sought to provide prompt treatment for them. Age-related alterations of functions in the immune system and lung parenchyma occur throughout life. Alterations with advancing age are promoted by various stimuli, including pathobionts, fungi, viruses, pollutants, and damage-associated molecular patterns derived from impaired cells, abandoned cell debris, and senescent cells. Age-related changes in the innate and adaptive immune response, termed immunosenescence, includes impairment of phagocytosis and antigen presentation, enhancement of proinflammatory mediator generation, and production of senescence-associated secretory phenotype. Immnunosenescence could promote inflammaging (chronic low-grade inflammation) and contribute to late-onset adult asthma and asthma in the elderly, along with age-related pulmonary disease, such as chronic obstructive pulmonary disease and pulmonary fibrosis, due to lung parenchyma senescence. Aged patients with asthma exhibit local and systemic type 2 and non-type 2 inflammation, associated with clinical manifestations. Here, we discuss immunosenescence’s contribution to the immune response and the combination of type 2 inflammation and inflammaging in asthma in the elderly and present an overview of age-related features in the immune system and lung structure. Full article

(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2021”)

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16 pages, 2061 KiB

Open AccessEditor’s ChoiceReview

Galectin-10 as a Potential Biomarker for Eosinophilic Diseases

by Hiroki Tomizawa, Yoshiyuki Yamada, Misaki Arima, Yui Miyabe, Mineyo Fukuchi, Haruka Hikichi, Rossana C. N. Melo, Takechiyo Yamada and Shigeharu Ueki

Biomolecules 2022, 12(10), 1385; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12101385 - 27 Sep 2022

Cited by 13 | Viewed by 3816

Abstract

Galectin-10 is a member of the lectin family and one of the most abundant cytoplasmic proteins in human eosinophils. Except for some myeloid leukemia cells, basophils, and minor T cell populations, galectin-10 is exclusively present in eosinophils in the human body. Galectin-10 forms [...] Read more.

Galectin-10 is a member of the lectin family and one of the most abundant cytoplasmic proteins in human eosinophils. Except for some myeloid leukemia cells, basophils, and minor T cell populations, galectin-10 is exclusively present in eosinophils in the human body. Galectin-10 forms Charcot–Leyden crystals, which are observed in various eosinophilic diseases. Accumulating studies have indicated that galectin-10 acts as a new biomarker for disease activity, diagnosis, and treatment effectiveness in asthma, eosinophilic esophagitis, rhinitis, sinusitis, atopic dermatitis, and eosinophilic granulomatosis with polyangiitis. The extracellular release of galectin-10 is not mediated through conventional secretory processes (piecemeal degranulation or exocytosis), but rather by extracellular trap cell death (ETosis), which is an active cell death program. Eosinophils undergoing ETosis rapidly disintegrate their plasma membranes to release the majority of galectin-10. Therefore, elevated galectin-10 levels in serum and tissue suggest a high degree of eosinophil ETosis. To date, several studies have shown that galectin-10/Charcot–Leyden crystals are more than just markers for eosinophilic inflammation, but play functional roles in immunity. In this review, we focus on the close relationship between eosinophils and galectin-10, highlighting this protein as a potential new biomarker in eosinophilic diseases. Full article

(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2021”)

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18 pages, 1278 KiB

Open AccessReview

Sex Plays a Multifaceted Role in Asthma Pathogenesis

by Tomomitsu Miyasaka, Kaori Dobashi-Okuyama, Kaori Kawakami, Chiaki Masuda-Suzuki, Motoaki Takayanagi and Isao Ohno

Biomolecules 2022, 12(5), 650; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12050650 - 29 Apr 2022

Cited by 8 | Viewed by 2944

Abstract

Sex is considered an important risk factor for asthma onset and exacerbation. The prevalence of asthma is higher in boys than in girls during childhood, which shows a reverse trend after puberty—it becomes higher in adult females than in adult males. In addition, [...] Read more.

Sex is considered an important risk factor for asthma onset and exacerbation. The prevalence of asthma is higher in boys than in girls during childhood, which shows a reverse trend after puberty—it becomes higher in adult females than in adult males. In addition, asthma severity, characterized by the rate of hospitalization and relapse after discharge from the emergency department, is higher in female patients. Basic research indicates that female sex hormones enhance type 2 adaptive immune responses, and male sex hormones negatively regulate type 2 innate immune responses. However, whether hormone replacement therapy in postmenopausal women increases the risk of current asthma and asthma onset remains controversial in clinical settings. Recently, sex has also been shown to influence the pathophysiology of asthma in its relationship with genetic or other environmental factors, which modulate asthmatic immune responses in the airway mucosa. In this narrative review, we highlight the role of sex in the continuity of the asthmatic immune response from sensing allergens to Th2 cell activation based on our own data. In addition, we elucidate the interactive role of sex with genetic or environmental factors in asthma exacerbation in women. Full article

(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2021”)

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9 pages, 826 KiB

Open AccessReview

Therapeutic Potential for Intractable Asthma by Targeting L-Type Amino Acid Transporter 1

by Keitaro Hayashi and Osamu Kaminuma

Biomolecules 2022, 12(4), 553; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12040553 - 8 Apr 2022

Cited by 1 | Viewed by 2582

Abstract

Bronchial asthma is a chronic disease characterized by airway inflammation, obstruction, and hyperresponsiveness. CD4⁺ T cells, particularly T helper (Th) 2 cells, and their specific cytokines are important mediators in asthma pathogenesis. However, it has been established that Th subsets, other than [...] Read more.

Bronchial asthma is a chronic disease characterized by airway inflammation, obstruction, and hyperresponsiveness. CD4⁺ T cells, particularly T helper (Th) 2 cells, and their specific cytokines are important mediators in asthma pathogenesis. However, it has been established that Th subsets, other than Th2, as well as various cell types, including innate lymphoid cells (ILCs), significantly contribute to the development of allergic inflammation. These cells require facilitated amino acid uptake to ensure their full function upon activation. Emerging studies have suggested the potential of pharmacological inhibition of amino acid transporters to inhibit T cell activation and the application of this strategy for treating immunological and inflammatory disorders. In the present review, we explore the possibility of targeting L-type amino acid transporter (LAT) as a novel therapeutic approach for bronchial asthma, including its steroid-resistant endotypes. Full article

(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2021”)

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Other

Jump to: Research, Review

6 pages, 1650 KiB

Open AccessCommentary

How Can Dupilumab Cause Eosinophilic Pneumonia?

by Momoko Kurihara, Katsunori Masaki, Emiko Matsuyama, Masato Fujioka, Reina Hayashi, Saki Tomiyasu, Kotaro Sasahara, Keeya Sunata, Masato Asaoka, Yuto Akiyama, Miyuki Nishie, Misato Irie, Takae Tanosaki, Hiroki Kabata and Koichi Fukunaga

Biomolecules 2022, 12(12), 1743; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12121743 - 23 Nov 2022

Cited by 8 | Viewed by 2776

Abstract

Reports of eosinophilic pneumonia (EP) as a side effect of dupilumab administration are limited in previous studies. Herein, we report two cases in which EP developed subsequent to the administration of dupilumab for eosinophilic chronic rhinosinusitis (ECRS). Case 1: A 55-year-old woman presented [...] Read more.

Reports of eosinophilic pneumonia (EP) as a side effect of dupilumab administration are limited in previous studies. Herein, we report two cases in which EP developed subsequent to the administration of dupilumab for eosinophilic chronic rhinosinusitis (ECRS). Case 1: A 55-year-old woman presented with ECRS, eosinophilic otitis media, and bronchial asthma, and was treated with dupilumab for ECRS. Five weeks later, fever and dyspnea developed, and infiltration shadows were observed in her lungs. The peripheral blood eosinophil count (PBEC) was 3848/μL (26%), bronchoalveolar lavage fluid showed eosinophilic infiltration, and EP was subsequently diagnosed. Her condition improved following prednisolone treatment. Case 2: A 59-year-old man presented with fatigue and dyspnea after receiving dupilumab for ECRS. He had infiltrative shadows throughout his left lung field, and his PBEC was 4850/μL (26.5%). Prednisolone was initiated, and his condition improved. EP developed in both patients during the period of elevated PBEC after dupilumab administration, and dupilumab was suspected to be the causative agent in their EP. Hence, EP should be considered as a differential diagnosis when fever and dyspnea appear following dupilumab administration. Full article

(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2021”)

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