Date: Monday, November 9, 2020
Session Title: Spondyloarthritis Including Psoriatic Arthritis – Basic Science Poster
Session Type: Poster Session D
Session Time: 9:00AM-11:00AM
Background/Purpose: Overexpression of KIR3DL2 on CD4+ T-cells and NK-cells has been reported in patients with ankylosing spondylitis (AS) HLAB27+. We aimed to 1) analyse KIR3DL2 expression in patients with active axial spondyloarthritis, radiographic (AS) and non radiographic (nr-axSpA), HLA B27+ and HLA B27 – and 2) to assess the impact of pharmacological stimulation on CD4+ T-cells of those patients.
Methods: We analysed by flow cytometry whole blood and PBMC samples from those patients using fluorescent antibodies against CD45, CD14, CD3, CD19, CD4, CD8, TCR GD, CD56, CD16, CD45RA, CXCR3, CCR6, KIR3DL1, KIR3DL2, IL17A, IL22, IL2, and IFN g. Positivity thresholds were set using control isotypes. Overnight pharmacological stimulation was performed with PMA/Ionomycin. All statistical analyses were performed using Graph Pad Prism (GraphPad Software, San Diego, CA). Paired data were analysed with Wilcoxon test, and unpaired data with Mann Whitney test. P values < 0.05 were considered to be significant.
Results: We included 16 AS, 4 nr-axSpA patients, all fulfilling the 2009 ASAS criteria and 5 healthy controls. Their main characteristics were: 11 HLA B27+, 9 HLA B27-, 14 males, mean disease duration of 15.23 years, mean BASDAI of 4.56/10, all csDMARD and bDMARD naive. Analysis of CD4+ T-cells and NK cells of our patients shows similar expression of KIR3DL2 both in HLA B27+, HLA B27- patients and healthy controls (Fig. 1). PMA/Ionomycin stimulation induced a significant increase of IL17A, IL22, IL2, and IFN gamma in CD4+ T cells of both HLA B27+ (p< 0.001, p< 0.001, p< 0.01, and p< 0.001 respectively) and HLA B27- patients (p < 0.05 for all) as well as an increased KIR3DL2 expression in both groups but only significant in the HLA B27+ one (p < 0.01) (Fig. 2). Concerning KIR3DL2+ CD4+ T-cells (Fig. 3A), significantly increased production of IL17A was observed in HLA B27+ patients (p < 0.01), while increase of IL2 and IL22 production was observed in both HLA B27+ (p < 0.01) and HLA B27- group (p < 0.05). Concerning activated CD4+ Th17 cells (Fig. 3B), significantly increased production of IL17A, IL2, and IFN gamma was observed in both HLA B27+ (p< 0.001, p< 0.01, and p< 0.001 respectively) and HLA B27- patients (p < 0.05 for all) as well as significantly increased production of IL22 in the HLA B27+ one only (p < 0.001). No significant overexpression of KIR3DL2 was observed in this cell subtype after stimulation. Furthermore, no statistically significant difference between HLAB27+ and HLAB27- patients was observed for all previously cited analysis, as well as between AS and nr-axSpA patients.
Conclusion: No overexpression of KIR3DL2 on CD4+ T-cells and NK cells was observed in patients with active axial spondyloarthritis whatever their phenotype (AS vs nr-axSpA) and their HLA B27 status.
Figure 1 : Expression of KIR3DL1 and KIR3DL2 on T-cells and NK cells.
Figure 2 : Cytokine production and KIR3DL2 expression on CD4+ T-cells upon PMA/Ionomycin stimulation
Figure 3 : A. Cytokine production by KIR3DL2+ CD4+ T-cells upon PMA/Ionomycin stimulation B. Cytokine production and KIR3DL2 expression on Th17 CD4+ T-cells upon PMA/Ionomycin stimulation
To cite this abstract in AMA style:Larid G, Trijau S, Barral C, Lafforgue P, Pham T. KIR3DL2 Is Not Overexpressed on CD4+ T Cells and NK Cells in Patients with Axial Spondyloarthritis csDMARD and bDMARD Naive [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/kir3dl2-is-not-overexpressed-on-cd4-t-cells-and-nk-cells-in-patients-with-axial-spondyloarthritis-csdmard-and-bdmard-naive/. Accessed March 23, 2023.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/kir3dl2-is-not-overexpressed-on-cd4-t-cells-and-nk-cells-in-patients-with-axial-spondyloarthritis-csdmard-and-bdmard-naive/