Evaluation of degranulation and cytokine production in natural killer cells from spondyloarthritis patients at single-cell level

Abstract

Background: A pathogenetic role of natural killer (NK) cells has been hypothesized in spondyloarthritides (SpA), but still conflicting data exist. Aim of this study was to investigate, in a cohort of SpA patients, the peripheral blood NK cell number, the cytokine production (IFNc and TNFa), and the cytotoxic activity on target cell stimulation. Moreover, we aimed to evaluate the expression of KIR3DL1, an inhibitory receptor binding HLA class I alleles, including HLA-B27 strongly associated with SpA, between different NK cell subsets.Methods: We enrolled 21 SpA patients and 21 healthy controls. Multicolor flow cytometry was used to analyze the cytokine levels triggered by activating receptors, the degranulation as CD107a surface expression on target cell stimulation, the number and KIR3DL1 expression on peripheral blood NK cells.Results: When stimulated with P815 cells preincubated with antibodies against activating receptors, NK cells produced IFNc to a lesser extent respect to healthy controls (P 5 0.0012). No differences were found in TNFa production and NK cell degranulation in patients and controls. We observed a higher frequency of KIR3DL1-positive NK cells from SpA patients than in controls (P 5 0.02). Similar results were obtained in NK cell subsets.Conclusions: In our SpA patients, we observed a reduced IFNc production, which may be explained by the elevated frequency of KIR3DL1-expressing NK cells, while the other parameters were similar to those of healthy controls. These results may support the role of NK cells in the pathogenesis of SpA, although more data are needed to substantiate these observations.

Natural killer cells in patients with severe chronic fatigue syndrome

“…Similarly, polymorphisms within the HLA-Bw4 may undermine recognition by KIR3DL1 [ 127 ]. Increases in KIR3DL1 have been associated with diseases such as HIV and spondyloarthritis [ 66 , 128 ]. KIR genes have previously been investigated in CFS patients where frequency of KIR3DS1 was significantly elevated in the CFS patients in comparison to the non-CFS group [ 65 ].…”

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

“…A recent study has also shown a decrease in IFNγ producing NK cell subset with normal NK cell degranulation in patients with AS [24]. In CIA mice model protective role of IFNγ producing NK cells was reported as NK cell depletion (IFNγ producing) resulted in increased IL-17 production by Th17 cells [29].…”

“…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].…”

An explorative study on deep profiling of peripheral leukocytes to identify predictors for responsiveness to anti-tumour necrosis factor alpha therapies in ankylosing spondylitis: natural killer cells in focus

“…The strong association between NK cells and the aetiology of AS is underlined by the capability of the disease-dependent elevated killer cell immunoglobulin-like receptors (KIRs) to recognise the HLA-B27 antigen, which is expressed in 80–90% of AS patients [ 48 , 49 ]. Concomitant with a pathogenetic upregulated frequency of KIR3DL1 + NK cells in AS, interferon (IFN)γ production is correspondingly diminished [ 50 ]. Moreover, activated KIR3DL2 + NK cells are increased in SpA and may play a pathogenic role.…”