Delgado-Dolset María Isabel, Obeso David, Sánchez-Solares Javier, Mera-Berriatua Leticia, Fernández Paloma, Barbas Coral, Fresnillo Miguel, Chivato Tomás, Barber Domingo, Escribese María M, Villaseñor Alma
Department of Basic Medical Sciences, Faculty of Medicine, Institute of Applied Molecular Medicine (IMMA), San Pablo CEU Universities, Madrid, Spain.
Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Faculty of Pharmacy, San Pablo CEU Universities, Madrid, Spain.
Front Mol Biosci. 2021 May 14;8:662792. doi: 10.3389/fmolb.2021.662792. eCollection 2021.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by persistent symptoms associated to the development of nasal polyps. To this day, the molecular mechanisms involved are still not well defined. However, it has been suggested that a sustained inflammation as allergy is involved in its onset. In this exploratory study, the aim was to investigate the effect of the allergic status in the development of CRSwNP. To achieve this, we recruited 22 patients with CRSwNP and classified them in non-allergic and allergic using ImmunoCAP ISAC molecular diagnosis. Plasma samples were analyzed using liquid chromatography coupled to mass spectrometry (LC-MS). Subsequently, significant metabolites from plasma that were commercially available were then analyzed by targeted analysis in some nasal polyps. Additionally, nasal polyp and nasal mucosa samples were examined for eosinophils, neutrophils, CD3 and CD11c cells, as well as collagen deposition and goblet cell hyperplasia. We found that 9 out of the 22 patients were sensitized to some aeroallergens (named as allergic CRSwNP). The other 13 patients had no sensitizations (non-allergic CRSwNP). Regarding metabolomics, bilirubin, cortisol, lysophosphatidylcholines (LPCs) 16:0, 18:0 and 20:4 and lysophosphatidylinositol (LPI) 20:4, which are usually related to a sustained allergic inflammation, were unexpectedly increased in plasma of non-allergic CRSwNP compared to allergic CRSwNP. LPC 16:0, LPC 18:0 and LPI 20:4 followed the same trend in nasal polyp as they did in plasma. Comparison of nasal polyps with nasal mucosa showed a significant increase in eosinophils ( < 0.001) and neutrophils ( < 0.01) in allergic CRSwNP. There were more eosinophils in polyps of non-allergic CRSwNP than in their nasal mucosa ( < 0.01). Polyps from non-allergic CRSwNP had less eosinophils than the polyps of allergic CRSwNP ( < 0.05) and reduced amounts of collagen compared to their nasal mucosa ( < 0.001). Our data suggests that there is a systemic inflammatory response associated to CRSwNP in the absence of allergy, which could be accountable for the nasal polyp development. Allergic CRSwNP presented a higher number of eosinophils in nasal polyps, suggesting that eosinophilia might be connected to the development of nasal polyps in this phenotype.
伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）的特征是与鼻息肉形成相关的持续症状。时至今日，其中涉及的分子机制仍未完全明确。然而，有研究表明，诸如过敏这样的持续性炎症参与了其发病过程。在这项探索性研究中，目的是调查过敏状态在CRSwNP形成中的作用。为此，我们招募了22例CRSwNP患者，并使用免疫捕获过敏原特异性IgE检测系统（ImmunoCAP ISAC）分子诊断将他们分为非过敏组和过敏组。血浆样本采用液相色谱-质谱联用（LC-MS）进行分析。随后，对血浆中可商购获得的显著代谢物在一些鼻息肉中进行靶向分析。此外，对鼻息肉和鼻黏膜样本进行嗜酸性粒细胞、中性粒细胞、CD3和CD11c细胞检查，以及胶原沉积和杯状细胞增生检查。我们发现，22例患者中有9例对某些气传过敏原致敏（称为过敏性CRSwNP）。另外13例患者未致敏（非过敏性CRSwNP）。关于代谢组学，通常与持续性过敏炎症相关的胆红素、皮质醇、溶血磷脂酰胆碱（LPC）16:0、18:0和20:4以及溶血磷脂酰肌醇（LPI）20:4，在非过敏性CRSwNP血浆中相较于过敏性CRSwNP意外升高。LPC 16:0、LPC 18:0和LPI 20:4在鼻息肉中的变化趋势与在血浆中一致。鼻息肉与鼻黏膜的比较显示，过敏性CRSwNP中嗜酸性粒细胞（<0.001）和中性粒细胞（<0.01）显著增加。非过敏性CRSwNP息肉中的嗜酸性粒细胞比其鼻黏膜中的更多（<0.01）。非过敏性CRSwNP的息肉中嗜酸性粒细胞比过敏性CRSwNP的息肉少（<0.05），且与鼻黏膜相比胶原含量减少（<0.001）。我们的数据表明，在无过敏的情况下，CRSwNP存在系统性炎症反应，这可能是鼻息肉形成的原因。过敏性CRSwNP鼻息肉中嗜酸性粒细胞数量更多，表明嗜酸性粒细胞增多可能与该表型鼻息肉的形成有关。
