Adult Allergy Service, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK.
Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Clin Exp Allergy. 2022 Dec;52(12):1432-1439. doi: 10.1111/cea.14136. Epub 2022 Apr 7.
Obesity-associated asthma (OA) is a difficult to treat asthma phenotype due to its severity and poor response to inhaled steroids. Early-onset allergic (EoOA) and late-onset non-allergic (LoOA) OA are suggested subtypes of this phenotype. Natural Killer (NK) cells are key elements of innate immunity involved in cytotoxicity and immune regulation, with uncertain role in OA pathogenesis.
Early-onset allergic and LoOA patients together with obese non-asthmatic (ONA) controls have been enrolled in the study. Peripheral blood samples have been collected for analysis. Percentages of total NK cells, CD3 CD56 and CD3 CD56 NK cell subsets, cytotoxic activity, intracellular interferon-γ, interleukin (IL)-10, IL-13, IL-17 secretion and activatory receptors (NKG2D, NKp46i and NKp44) have been investigated by flow cytometry. The effect of IL-12 and IL-23 stimulation on NK cells and intracellular cytokines in different groups have also been analysed and compared with unstimulated conditions.
Results of ONA (n = 5, age 42 ± 8), EoOA (n = 5, age 42 ± 10) and LoOA (n = 8, age 46 ± 8) patients have analysed. Body Mass Index has been found to be negatively correlated with CD69 (p = .022, r = -0.534). NKG2D receptor has been significantly low in CD56 cells of asthma population (p = .046). NKp44 receptor expression has increased after IL-12 stimulation in EoOA and control group (p = .02). Intracellular IL-10 content has increased in LoOA and control subjects (p = .018, p = .03) but not in the EoOA group. Intracellular IL-17 level has found be higher in allergic OA group. LoOA patients showed a decreased NK cytotoxicity compared with the early-onset asthma group (p = .05).
Our study suggests an impaired NK receptor expression, activation and reduced cytotoxicity in OA patients together with variances between different subtypes of this phenotype. This data would be beneficial for tailoring a more personalized treatment strategy combatting steroid resistance and frequent exacerbations in this group of patients.
肥胖相关性哮喘（OA）是一种难以治疗的哮喘表型，因其严重程度和对吸入性类固醇的反应不佳而导致。早发性过敏（EoOA）和迟发性非过敏（LoOA）OA 被认为是这种表型的亚型。自然杀伤（NK）细胞是参与细胞毒性和免疫调节的固有免疫的关键元素，其在 OA 发病机制中的作用尚不确定。
将早发性过敏和 LoOA 患者与肥胖非哮喘（ONA）对照者一起纳入研究。采集外周血样本进行分析。通过流式细胞术检测总 NK 细胞、CD3 CD56 和 CD3 CD56 NK 细胞亚群、细胞毒性活性、细胞内干扰素-γ、白细胞介素（IL）-10、IL-13、IL-17 分泌和激活受体（NKG2D、NKp46i 和 NKp44）的百分比。还分析了不同组在 IL-12 和 IL-23 刺激下对 NK 细胞和细胞内细胞因子的影响，并与未刺激条件进行了比较。
分析了 ONA（n=5，年龄 42±8）、EoOA（n=5，年龄 42±10）和 LoOA（n=8，年龄 46±8）患者的结果。发现体重指数与 CD69 呈负相关（p=0.022，r=-0.534）。哮喘患者的 CD56 细胞中 NKG2D 受体显著降低（p=0.046）。EoOA 和对照组经 IL-12 刺激后 NKp44 受体表达增加（p=0.02）。IL-10 细胞内含量在 LoOA 和对照组中增加（p=0.018，p=0.03），但在 EoOA 组中没有增加。过敏性 OA 组中 IL-17 细胞内水平较高。LoOA 患者的 NK 细胞毒性较早发性哮喘组降低（p=0.05）。
我们的研究表明 OA 患者的 NK 受体表达、激活和细胞毒性受损，以及这种表型的不同亚型之间存在差异。这些数据将有助于为该组患者制定更个性化的治疗策略，以对抗类固醇耐药和频繁恶化。
