Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis

Background

IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS).

Association between impaired IL-10 production following exposure to Staphylococcus aureus enterotoxin B and disease severity in eosinophilic chronic rhinosinusitis

Background

IL-10 is a major anti-inflammatory cytokine that prevents inflammation-mediated tissue damage. We characterized the production of IL-10 by sinonasal tissue cells following exposure to Staphylococcus aureus enterotoxin B (SEB), which elicits cellular responses and is associated with the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS).

Eosinophilic chronic rhinosinusitis

Eosinophilic chronic rhinosinusitis (ECRS) is a subgroup of chronic rhinosinusitis with nasal polyps (CRSwNP), which is associated with severe eosinophilic infiltration and intractable. Its symptoms include dysosmia, nasal obstruction, and visous nasal discharge. The cause of ECRS is not clear, although it is thought that Staphylococcus aureus and its enterotoxins are involved in stimulating the Th2 system to promote IgE production and eosinophil infiltration through various pathways. While, the coagulation system is activated and the fibrinolytic system is suppressed, leading to deposition of fibrinous networks in nasal polyps. Therefore, a fibrin-degrading agent could be a new treatment for ECRS.Genetic analysis of nasal polyp cells using next-generation sequencing has identified some of the factors involved in ECRS, including periostin, which can be used as a biomarker of this condition. A protease inhibitor could be a therapeutic agent for ECRS. Regarding the role of eosinophils, many researchers have been interested in the mechanism of ETosis. However, the mechanism leading to development of nasal polyps is unknown.In Japan (as well as in East Asia), the incidence of non-ECRS is decreasing and that of ECRS is increasing, but the reason is also unknown. Thanks to the development of biologics therapy, it is thought that there will be a shift to precision medicine in the future.     

Mixed cell type in airway inflammation is the dominant phenotype in asthma patients with severe chronic rhinosinusitis

BackgroundAsthma often coexists with chronic rhinosinusitis (CRS). Recent studies revealed that sinus inflammation in asthmatic patients was related to eosinophilic inflammation. However, the relationship between the severity of CRS and four different sputum inflammatory phenotypes as defined by the proportion of eosinophils and neutrophils is unknown. The aim of this study was to examine the impact of the severity of CRS on lower airway and systemic inflammation in asthmatic patients.MethodsWe enrolled 57 adult asthmatic patients who underwent sinus computed tomography (CT). The severity of CRS was evaluated by the Lund-Mackay score (LMS). The induced sputum inflammatory phenotype was defined by eosinophils (≥/<2%) and neutrophils (≥/<60%). Peripheral blood mononuclear cells (PBMC) were collected to examine cytokine productions.ResultsThe median LMS of subjects was 6 (interquartile range, 0–11.5). The sputum inflammatory cell phenotype was categorized as paucicellular (n = 14), neutrophilic (n = 11), eosinophilic (n = 20), or mixed (n = 12). LMS was positively correlated with the percentage of blood eosinophils, sputum eosinophils, and mean fluorescence intensity (MFI) of IL-5 on CD4⁺ T cells. In the severe CRS group (LMS, 12–24), the number of mixed cellular phenotypes was higher than that in the group without CRS (LMS, 0–4) and mild-to-moderate CRS group (LMS, 5–11).ConclusionsIn asthmatic patients with severe CRS, the proportion of the mixed cellular inflammatory phenotype was increased as well as eosinophilic inflammation.