A significantly impaired natural killer cell activity due to a low activity on a per-cell basis in rheumatoid arthritis

Abstract

To elucidate the characterization of peripheral natural killer (NK) cells in patients with rheumatoid arthritis (RA), we investigated the NK cell activity, the expression of NK cell activating receptors and intracellular molecules. The NK activity was analyzed in 27 RA patients, 22 primary Sjögren's syndrome (SS) patients, and 15 healthy individuals using the (51)Chrominium release assay. The expression of NK cell activating receptors (NKG2D, CD244, CD2, and CD16) and intracellular molecules (granzyme B, perforin, and TCR zeta chain) in CD3-CD56+ cells were characterized by flow cytometry. The serum cytokine levels (IL-6, TNFalpha, and IL-18) were measured using ELISA. Both the NK cell activity and the activity on a per-cell basis were observed to significantly decrease in the RA patients in comparison to the controls. The expression of NKG2D and CD244 also significantly decreased in both the RA and primary SS patients, whereas the significant decrease in the CD16 expression was only observed in the RA patients. The titer of the serum IL-6, TNFalpha, and IL-18 was significantly higher in the RA patients than in the controls. These data suggest that a low NK activity on a per-cell basis might therefore contribute to an impaired NK activity in the patients with RA.

Collagen-induced arthritis: severity and immune response attenuation using multivalent N-acetyl glucosamine

“…We consider these findings important with regard to the negative effect of NKG2D on autoimmunity development reported previously [31,33]. Evaluating NK cytotoxicity, however, we also detected the suppression of NK effector function appearing during the disease progression, as reported by Aramaki et al in human RA [21] or Lo et al in CIA [22]. During the early arthritis phase the cytotoxicity was at the HC level, while in the late arthritis phase it showed a highly significant suppression.…”

“…Corresponding results were also presented by Dalbeth and Callan, who suggested that NK cells in the inflamed synovium interact with the macrophage/monocyte population, thus amplifying the production of inflammatory cytokines [20]. Conversely, Aramaki et al reported low, impaired NK activity in human RA [21]. Lo et al even reported that NK cells play a protective role in the development of CIA, which is mediated by interferon (IFN)-γ production suppressing the generation of Th17 cells [22].…”

Natural killer cells

“…In many instances of autoimmune disease, a reduction in number of NK cells along with decreased cytotoxic function has been observed. 43,44 In vivo studies using experimental autoimmune encephalomyelitis (EAE), which is an animal model of multiple sclerosis (MS), show increased severity and mortality when NK cells are depleted prior to disease induction. EAE animals have cellular infiltration, CNS inflammation, and demylination.…”

Natural killer cell and gamma delta T cell alterations in enthesitis related arthritis category of juvenile idiopathic arthritis

“…Low perforin expressing NK cells have been reported previously in RA and systemic onset JIA. Further using functional assay reduced cytotoxicity has been seen in patients with SoJIA as well as RA [9,20,21,23,24]. A recent study on AS using degranulation assay also reported impaired NK cell cytotoxicity [24].…”