Publications by authors named "G Holtappels"
Context: Recent insights into type 2 inflammation have led to the development of monoclonal antibody therapies for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Despite add-on therapy with a monoclonal antibody, some individuals remain uncontrolled in terms of upper and/or lower airway symptoms, prompting an exploration of the efficacy of combining biological therapies and their impact on inflammatory pathways.
Objectives: In this article, we present a distinctive case of a patient with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, who experienced substantial clinical and local inflammatory improvements through dual monoclonal antibody therapy.
Article Synopsis
- Vaccines need to encourage mucosal immunity to effectively prevent infection by respiratory viruses, but the impact of current mRNA COVID-19 vaccines on this type of immunity is not well understood.
- A study with 183 individuals revealed that repeated mRNA booster vaccinations significantly increased neutralizing antibodies in nasal secretions, suggesting a connection between nasal and serum antibody levels.
- Further research in a mouse model indicated that the antibodies linked to mucosal immunity come from the spleen and bone marrow and can migrate from the bloodstream to the respiratory mucosa, providing insights for future vaccine development.
Article Synopsis
- - ILC2s are important for type 2 immunity and play a role in chronic inflammatory conditions like asthma.
- - Research shows that resting ILC2s in humans retain a marker (CD45RO) associated with activated inflammatory ILC2s, while also decreasing another typical marker (CD127) in specific tissues.
- - When isolated and stimulated, these CD127-CD45RO+ ILC2s demonstrate enhanced growth and cytokine production, suggesting that human ILC2s can develop an innate immune memory, prompting a reevaluation of how these cells are identified.
Background: The expression of MZB1 genes is significantly elevated in patients who have chronic rhinosinusitis with nasal polyp (CRSwNP) disease compared with healthy controls.
Objective: To characterize MZB1-positive B cells in CRSwNP and to estimate the contribution of distinct subsets of B cells to the local overproduction of immunoglobulins.
Methods: Single-cell RNA-sequencing with Cellular Indexing of Transcriptomes and Epitopes by Sequencing technology, Switching Mechanism At the 5' end of RNA Template sequencing, flow cytometry, immunohistochemistry and immunofluorescence staining, Western blot, QuantiGene Plex assay, B-cell ImmunoSpot assay, Luminex assay, and enzyme-linked immunosorbent assay were performed.
Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with elevated levels of type 2 inflammatory cytokines and raised immunoglobulin concentrations in nasal polyp tissue. By using single-cell RNA sequencing, transcriptomics, surface proteomics, and T cell and B cell receptor sequencing, we found the predominant cell types in nasal polyps were shifted from epithelial and mesenchymal cells to inflammatory cells compared to nasal mucosa from healthy controls. Broad expansions of CD4 T effector memory cells, CD4 tissue-resident memory T cells, CD8 T effector memory cells and all subtypes of B cells in nasal polyp tissues.
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