Omalizumab effectively protects against early and late allergic responses in asthma after 4 weeks

Trischler, Jordis; Lieb, Adrian; Arnold, Marcel; Schulze, Johannes; Rosewich, Martin; Schubert, Ralf; Bottoli, Ivan; Zielen, Stefan

doi:10.1111/all.13217

Cited by 14 publications

(12 citation statements)

References 10 publications

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“…The disease is characterized by shortness of breath, wheeze, cough, reduced airflow on expiration, and airway hyperresponsiveness to nonspecific bronchoconstrictors (1)(2)(3)(4). The complex mechanisms of asthma initiation and progression have been extensively studied for several decades, and many research discoveries have been used in the pre-and clinical settings as therapeutic agents for disease immunotherapy (5)(6)(7)(8)(9). Despite these significant advances in research and therapy, the increase in asthma rates is a worldwide phenomenon and no cure for the disease is currently available (10).…”

Section: Introductionmentioning

confidence: 99%

Semaphorin 4A Stabilizes Human Regulatory T Cell Phenotype via Plexin B1

Chapoval

Hritzo

et al. 2019

ImmunoHorizons

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We previously reported that neuroimmune semaphorin (Sema) 4A regulates the severity of experimental allergic asthma and increases regulatory T (Treg) cell numbers in vivo; however, the mechanisms of Sema4A action remain unknown. It was also reported that Sema4A controls murine Treg cell function and survival acting through neuropilin 1 (NRP-1) receptor. To clarify Sema4A action on human T cells, we employed T cell lines (HuT78 and HuT102), human PBMCs, and CD4 + T cells in phenotypic and functional assays. We found that HuT78 demonstrated a T effector-like phenotype (CD4 + CD25 low Foxp3 2), whereas HuT102 expressed a Treg-like phenotype (CD4 + CD25 hi Foxp3 +). Neither cell line expressed NRP-1. HuT102 cells expressed Sema4A counter receptor Plexin B1, whereas HuT78 cells were Sema4A +. All human peripheral blood CD4 + T cells, including Treg cells, expressed PlexinB1 and lacked both NRP-1 and-2. However, NRP-1 and Sema4A were detected on CD3 negative CD4 intermediate human monocytes. Culture of HuT cells with soluble Sema4A led to an upregulation of CD25 and Foxp3 markers on HuT102 cells. Addition of Sema4A increased the relative numbers of CD4 + CD25 + Foxp3 + cells in PBMCs and CD4 + T cells, which were NRP-1 negative but PlexinB1 + , suggesting the role of this receptor in Treg cell stability. The inclusion of anti-PlexinB1 blocking Ab in cultures before recombinant Sema4A addition significantly decreased Treg cell numbers as compared with cultures with recombinant Sema4A alone. Sema4A was as effective as TGF-b in inducible Treg cell induction from CD4 + CD25 depleted cells but did not enhance Treg cell suppressive activity in vitro. These results suggest strategies for the development of new Sema4A-based therapeutic measures to combat allergic inflammatory diseases. ImmunoHorizons, 2019, 3: 71-87.

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Section: Introductionmentioning

confidence: 99%

Semaphorin 4A Stabilizes Human Regulatory T Cell Phenotype via Plexin B1

Chapoval

Hritzo

et al. 2019

ImmunoHorizons

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“…Omalizumab is a humanized monoclonal antibody that binds to constant region 3 (Cε3) of IgE and blocks this protein from binding to its receptor that is located on mast cells and basophils. It is administered subcutaneously and is approved in the European Union and USA for the treatment of severe allergic asthma with high levels of aero‐allergen specific IgE and chronic spontaneous urticaria . Its intranasal application is under investigation for treatment of allergic rhinitis as well .…”

Section: Precision Medicine In Crsmentioning

confidence: 99%

Novel findings in immunopathophysiology of chronic rhinosinusitis and their role in a model of precision medicine

Ong

Wang

2019

Allergy

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Our understanding of the pathophysiology of chronic rhinosinusitis (CRS) is continuously evolving. The traditional description of CRS in terms of two phenotypes based on the presence or absence of nasal polyps belies the underlying intricate immunopathophysiological processes responsible for this condition. CRS is being increasingly recognized as a disease spectrum encompassing a range of inflammatory states in the sinonasal cavity, with non-type 2 inflammatory disease on one end, type 2 inflammatory, eosinophil-heavy disease on the other and an overlap of both in different proportions in between. Abundance in research on the immune mechanisms of CRS has revealed various new endotypes that hold promise as biomarkers for the development of targeted therapies in severe, uncontrolled CRS. The introduction of precision medicine to manage this chronic, complex condition is a step forward in providing individualized care for all patients with CRS. In this review, the latest research on the pathophysiology of CRS with a focus on potential novel biomarkers and treatment options over the last 2 years are summarized and integrated into a suggested model of precision medicine in CRS. K E Y W O R D S biomarkers, chronic rhinosinusitis, endotypes, immunopathophysiology, precision medicine

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“…Currently, omalizumab is the only efficacious IgE-targeting antibody licensed for the treatment of allergic asthma and chronic spontaneous urticaria (124)(125)(126)(127)(128)(129)(130). Preliminary data indicate that patients suffering from systemic mastocytosis may also benefit from omalizumab treatment (131).…”

Section: Targeting Ige and Ige-expressing B Cellsmentioning

confidence: 99%