Background/Purpose:  Enthesitis Related Arthritis (ERA) is the most common form of Juvenile Idiopathic Arthritis (JIA) in India. ERA is associated with increased frequency of Th17 cells and synovial fluid (SF) IL-17 levels. Recently innate immune cells like Natural Killer (NK) cells, γδ T cells have been reported to produce IL-17 and contribute to disease pathogenesis in Ankylosing spondylitis. Thus we have studied the frequency and effector functions of innate cells in ERA.

Methods: Fifty JIA-ERA, 21 other JIA patients (disease controls) and 25 healthy controls were enrolled in the study and peripheral blood (PB) was collected.19 paired synovial fluids were also studied. Frequency of NK cells, NKT cells, γδ T cells, expression of perforin in NK cells and KIR3DL1/2 on NK cell and T cells were measured by flow cytometry. Frequency of IL-17 producing T cells, NK cells and γδ T cells were quantified by Flow cytometry.

Results: Patients with ERA as compared with healthy controls had normal frequency of NK cells (9.52% ± 4.67 v/s 9.62% ± 2.65) and NKT cells (2.93% ± 1.96 v/s 2.42% ± 1.78) but had increased frequency of γδ T cells (9.31% ± 4.61 v/s 5.12% ± 2.61; p<0.001). Further NK cells in ERA patients had low expression of perforin (56.19% ± 15.67) and high KIR3DL1/2 expression (31.33% ± 12.13) as compared to controls (82.79% ± 9.43; p < 0.001, 21.32% ± 11.05, p=0.001 respectively). Frequency of IL-17 producing NK cells were increased in PB of JIA-ERA patients (n=10, 3.69% ± 2.72) as compared to healthy controls (n= 6, 0.83% ± 0.80; p = 0.01). Also the IL-17 producing γδ T cells were high in JIA-ERA (2.22% ± 2.20) than healthy controls (0.35% ± 0.56, p=0.02). In paired samples the frequencies of these cells were similar but as compared to PB,SF NK cells had reduced expression of perforin (56.64% ± 17.08 v/s 1.55% ± 2.5, p=0.001)and KIR3DL (31.39 ± 9.66 v/s 10.89% ± 10.84, p < 0.001).

 Conclusion: NK cells in ERA patients have CD56 bright phenotype with low perforin expression suggestive of cytokine producing cells. Further increase in KIR3DL1/2 expression on NK cells suggests that they may interact with HLA B27 and have enhanced survival. Increased frequency of IL-17 producing NK cells and γδ T cells in ERA suggests that in addition to Th17 cells they may also contribute to IL-17 in ERA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-natural-killer-cells-and-gamma-delta-t-cells-in-enthesitis-related-arthritis-category-of-juvenile-idiopathic-arthritis/