Characteristics of Circulating Natural Killer Cells and Their Interferon-γ Production in Active Adult-onset Still Disease

• Published in: Journal of rheumatology 2019-10, Vol.46 (10), p.1268-1276
• Main Authors: Shimojima, Yasuhiro, Kishida, Dai, Ueno, Ken-Ichi, Ushiyama, Satoru, Ichikawa, Takanori, Sekijima, Yoshiki
• Format: Article
• Language: English
• ISSN: 0315-162X; 1499-2752
• DOI: 10.3899/jrheum.181192

To investigate the characteristics of circulating natural killer (NK) cells and their interferon (IFN)-γ-producing ability in adult-onset Still disease (AOSD). Peripheral blood mononuclear cells were obtained from 22 patients in the acute phase of AOSD (acute AOSD); 7 of the 22 patients after treatment (remission AOSD), and 11 healthy controls (HC). NK cells and their IFN-γ expression levels were analyzed by flow cytometry. Additionally, the cytokine receptors of interleukin (IL)-12, IL-15, and IL-18 on NK cells were also evaluated. The frequency of NK cells was significantly lower in acute AOSD than in HC. NK cell counts significantly increased in remission AOSD. Expression of IL-12 and IL-15 receptors on NK cells was significantly increased in acute AOSD, whereas that of IL-18 receptor indicated no significant difference among 3 groups. IFN-γ expression in NK cells was significantly higher in acute AOSD than in HC, and significantly decreased in remission AOSD. The absolute number of NK cells and IFN-γ-expressing NK cells revealed an inverse correlation with serum ferritin levels in acute AOSD. In 2 distinct subsets of NK cells, CD56 NK cells significantly exhibited higher IFN-γ expression than CD56 NK cells in acute AOSD. In acute AOSD, NK cells displayed lower proportion, whereas they had higher ability for IFN-γ production than in HC; moreover, upregulation of IL-12 and IL-15 receptors on NK cells may promote IFN-γ production. In addition, disease activity may be implicated in regulating the number of NK cells and IFN-γ-expressing NK cells in AOSD.