Ryu Gwanghui, Kim Dong Kyu, Dhong Hun Jong, Eun Kyoung Mi, Lee Kyung Eun, Kong Il Gyu, Kim HyoYeol, Chung Seung Kyu, Kim Dong Young, Rhee Chae Seo, Cho Seong Ho, Hong Sang Duk, Kim Dae Woo
Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Cheonan, Korea.
Department of Otorhinolaryngology-Head and Neck Surgery and Institute of New Frontier Research, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea.
Allergy Asthma Immunol Res. 2019 Sep;11(5):664-676. doi: 10.4168/aair.2019.11.5.664.
Despite medical and surgical treatments, some cases of nasal polyps (NP) exhibit recidivism. However, the endotype of refractory chronic rhinosinusitis with NP (CRSwNP) remains unclear. Therefore, the objective of this study was to characterize the immunological profile of refractory CRSwNP.
The control (n =23), primary NP group (pNP, n =70) and refractory NP group (rNP, n =86) were enrolled in this study. Patients who underwent revision surgeries due to failed maximal medical treatment after primary surgery were defined as the rNP group. A total of 18 inflammatory markers were investigated in nasal tissues using multiplex cytokine assay or enzyme-linked immunosorbent assay.
The clinical characteristics of rNP included more extensive disease and worse clinical course after surgery. Additionally, rNP subjects showed higher infection rate (mucopurulence and culture-positive rate), more frequent use of antibiotics and suffered from symptomatic bacterial infection, increased asthma morbidity compared to pNP. Cytokine profile analysis showed that levels of Th17-associated mediators (myeloperoxidase, interleukin (IL)-8, IL-17A and IL-23), B-cell activating factor (BAFF) and Th1 cytokine (interferon-γ) were up-regulated in rNP compared to controls and pNP. Human neutrophil elastase-positive cells were also enhanced in rNP compared with pNP. Upregulation of Th17/Th1mediators and BAFF were observed in rNP, regardless of tissue eosinophilia or asthmatic comorbidity. Interestingly, eosinophilic markers, such as eosinophil cationic protein and C-C motif chemokine ligand 24, were up-regulated in asthmatic rNP compared to pNP and controls. Levels of anti-dsDNA immunoglobulin (Ig) G and IgA were up-regulated in rNP and highest in asthmatic eosinophilic rNP among subtypes of rNP.
Our results suggest that Th17/Th1-associated mediators and BAFF may play a role and be a potential therapeutic target in refractory CRSwNP. Additionally, eosinophilic markers and autoantibodies may contribute to refractoriness in asthmatic rNP.
尽管采取了药物和手术治疗，但一些鼻息肉（NP）病例仍会复发。然而，难治性慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）的内型仍不清楚。因此，本研究的目的是明确难治性CRSwNP的免疫特征。
本研究纳入了对照组（n = 23）、初发性NP组（pNP，n = 70）和难治性NP组（rNP，n = 86）。因初次手术后最大程度药物治疗失败而接受翻修手术的患者被定义为rNP组。使用多重细胞因子检测或酶联免疫吸附测定法对鼻组织中的18种炎症标志物进行了研究。
rNP的临床特征包括疾病范围更广以及术后临床病程更差。此外，rNP患者的感染率更高（黏液脓性和培养阳性率），更频繁使用抗生素且患有症状性细菌感染，与pNP相比哮喘发病率增加。细胞因子谱分析显示，与对照组和pNP相比，rNP中与Th17相关的介质（髓过氧化物酶、白细胞介素（IL）-8、IL-17A和IL-23）、B细胞活化因子（BAFF）和Th1细胞因子（干扰素-γ）水平上调。与pNP相比，rNP中人类中性粒细胞弹性蛋白酶阳性细胞也增多。无论组织嗜酸性粒细胞增多或合并哮喘，rNP中均观察到Th17/Th1介质和BAFF上调。有趣的是，与pNP和对照组相比，哮喘性rNP中的嗜酸性粒细胞标志物，如嗜酸性粒细胞阳离子蛋白和C-C基序趋化因子配体24上调。在rNP中，抗双链DNA免疫球蛋白（Ig）G和IgA水平上调，在rNP亚型中，哮喘性嗜酸性粒细胞性rNP中最高。
我们的结果表明，Th17/Th1相关介质和BAFF可能在难治性CRSwNP中起作用，并且是潜在的治疗靶点。此外，嗜酸性粒细胞标志物和自身抗体可能导致哮喘性rNP的难治性。
