Department of Rheumatology, Wonju Christian Hospital, Wonju College of Medicine, Yonsei University, Wonju City, Kangwon-do, South Korea.
J Rheumatol. 2012 Oct;39(10):2000-7. doi: 10.3899/jrheum.111500. Epub 2012 Aug 1.
To investigate natural killer (NK) cell proportions, NK cell cytotoxicity, and interleukin 18 (IL-18) expression, in patients with adult-onset Still's disease (AOSD).
Forty-five patients with AOSD (active = 22, inactive = 23) and 32 healthy controls were included. The proportions of NK cells among peripheral blood mononuclear cells were assessed by flow cytometry. IL-18 and IL-18-binding protein (IL-18BP) concentrations were measured by ELISA. Twenty-four patients with AOSD and 18 controls were examined for cytotoxic activity of NK cells by co-incubating NK cells with NK-sensitive K562 cells. The association of NK cell function with clinical and laboratory measures was investigated.
The proportions of NK cells were significantly lower in patients with active AOSD than in patients with inactive disease and controls. NK cell cytotoxic function was significantly lower in patients with AOSD than in controls. NK cell proportions and cytotoxic functions were reexamined in 11 and 6 patients, respectively, after treatment. Low NK cell proportion and cytotoxic dysfunction were improved with clinical improvements of the patients. IL-18 and IL-18BP levels were much higher in patients with active AOSD than in controls. NK cell cytotoxic functions were consistently low and IL-18 and IL-18BP levels were constantly high in patients with AOSD, regardless of disease activity.
Low NK cell proportion, defective cytotoxic function, and elevated IL-18 levels may be significant features of AOSD. After resolution of the acute phase, low NK cell proportion was recovered and NK cell cytolytic function was restored along with clinical improvement. These findings possibly contribute to immunologic abnormalities in AOSD.
研究自然杀伤 (NK) 细胞比例、NK 细胞细胞毒性和白细胞介素 18 (IL-18) 表达在成年Still 病 (AOSD) 患者中的变化。
纳入 45 例 AOSD 患者(活动期=22 例,缓解期=23 例)和 32 例健康对照者。采用流式细胞术检测外周血单个核细胞中 NK 细胞的比例。采用 ELISA 法检测 IL-18 和 IL-18 结合蛋白 (IL-18BP) 的浓度。对 24 例 AOSD 患者和 18 例对照者的 NK 细胞的细胞毒性活性进行检测,即将 NK 细胞与 NK 敏感的 K562 细胞共孵育。探讨 NK 细胞功能与临床和实验室指标的关系。
活动期 AOSD 患者的 NK 细胞比例明显低于缓解期患者和对照组。AOSD 患者的 NK 细胞细胞毒性功能明显低于对照组。治疗后分别对 11 例和 6 例患者重新检测 NK 细胞比例和细胞毒性功能。患者的临床改善后,NK 细胞比例低和细胞毒性功能障碍得到改善。活动期 AOSD 患者的 IL-18 和 IL-18BP 水平明显高于对照组。AOSD 患者的 NK 细胞细胞毒性功能持续低下,IL-18 和 IL-18BP 水平持续升高,与疾病活动无关。
NK 细胞比例低、细胞毒性功能缺陷和 IL-18 水平升高可能是 AOSD 的重要特征。急性相缓解后,NK 细胞比例恢复,NK 细胞细胞毒性功能随着临床改善而恢复。这些发现可能有助于解释 AOSD 的免疫异常。