Supplementary Material for: CD48 Expression on Eosinophils in Nasal Polyps of Chronic Rhinosinusitis Patients

<b><i>Introduction:</i></b> The pathogenesis of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNPs) is not yet completely understood. Based on current knowledge, the infiltration of mast cells and eosinophils in nasal polyps (NPs) plays an important role. This study aimed to investigate the interplay of asthma and allergy etiopathology in CRSwNPs patients by specifically studying tissue mast cells and eosinophils and the pro-inflammatory marker CD48. <b><i>Methods:</i></b> Immunohistochemistry was used to assess eosinophils, mast cells, and CD48 expressing eosinophils infiltrating NPs, and flow cytometry was used to assess surface receptors expression on eosinophils from digested NPs. <b><i>Results:</i></b> Immunohistochemical analyses showed that mast cell infiltration in NPs is higher in allergic patients in comparison to nonallergic patients; eosinophils infiltration in asthmatic NPs was significantly elevated in comparison to the nonasthmatic NPs, and membrane CD48 (mCD48) expression on eosinophils infiltrating nonallergic asthmatic NPs was highly elevated in comparison to the other subgroups. Similarly, mCD48 and its high-affinity ligand m2B4’s expression on eosinophils from enzymatically digested NPs were significantly higher in nonallergic asthmatics in comparison to allergic asthmatics. <b><i>Conclusions:</i></b> Eosinophil infiltration in NPs for asthmatic patients, and mast cell infiltration for allergic patients, may be used as reliable biomarkers for endotyping CRSwNPs. In addition, CD48 in asthmatic patients who developed CRSwNPs could be regarded as a potential target for treatment.

<b><i>引言：</i></b> 伴鼻息肉的慢性鼻-鼻窦炎（chronic rhinosinusitis with nasal polyps, CRSwNPs）的发病机制尚未完全阐明。基于现有认知，鼻息肉（nasal polyps, NPs）中肥大细胞（mast cells）与嗜酸性粒细胞（eosinophils）的浸润发挥着重要作用。本研究旨在通过针对性分析组织肥大细胞、嗜酸性粒细胞及促炎标志物CD48，探讨哮喘与变态反应病因在CRSwNPs患者发病机制中的相互作用。<b><i>方法：</i></b> 采用免疫组织化学法检测浸润鼻息肉的嗜酸性粒细胞、肥大细胞及表达CD48的嗜酸性粒细胞；采用流式细胞术分析酶解消化鼻息肉所得嗜酸性粒细胞的表面受体表达情况。<b><i>结果：</i></b> 免疫组织化学分析显示，变态反应性患者鼻息肉中的肥大细胞浸润水平显著高于非变态反应性患者；哮喘患者鼻息肉的嗜酸性粒细胞浸润水平显著高于非哮喘患者鼻息肉；非变态反应性哮喘患者鼻息肉浸润嗜酸性粒细胞的膜型CD48（mCD48）表达水平显著高于其他亚组。类似地，对酶解消化鼻息肉所得嗜酸性粒细胞进行分析发现，非变态反应性哮喘患者的嗜酸性粒细胞表面膜型CD48及其高亲和力配体m2B4的表达水平显著高于变态反应性哮喘患者。<b><i>结论：</i></b> 哮喘患者鼻息肉中的嗜酸性粒细胞浸润、变态反应患者鼻息肉中的肥大细胞浸润，可作为CRSwNPs分型诊断的可靠生物标志物。此外，伴CRSwNPs的哮喘患者体内CD48可作为潜在治疗靶点。