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Abstract
Background Natural killer T (NKT) cells are a unique subgroup of T cells that represents a bridge between innate and adaptive immunity. The functions of NKT-cells are regulated by the balance between activating and inhibitory Killer cell immunoglobulin-like receptors (KIRs). Systemic lupus erythematosus (SLE) patients showed aberrant expression of KIRs on NKT-cells. Whether the expression pattern of KIRs on NKT-cells is associated with disease activity in SLE is still unknown.
Objectives Assessment of expression of stimulatory and inhibitory KIRs on NKT-cells in SLE patients and its relation to disease activity.
Methods We recruited 40 SLE patients and 20 age and gender matched healthy controls. According to SLE disease activity index (SLEDAI), patients were divided into two groups; active SLE (n=20) and inactive SLE (n=20). SLE was active when SLEDAI was ≥4. Immuno-phenotyping by flow cytometry was done using markers for NKT-cells (CD3 and CD56), stimulatory KIRs (KIR2DL4, CD158D) and inhibitory KIRs (KIR3DL1, CD158E1). Absolute counts and percentage of NKT cells expressing CD158D and CD158E1 together with their mean fluorescence intensity (MFI) were measured. The histogram of CD158 expression was used to assess KIRs on NKT cells.
Flow cytometry charts of lymphocytes and NKT cells in SLE patients (active and inactive) and controls are shown in (Figure 1).
Laboratory work included ANA, anti-dsDNA, Anti-smith, C3, C4, CRP and ESR.
Results Mean age of patients was 29.9±10.8 years. Females constituted 95% (n=38) of patients. Mean disease duration was 4.4±4.5 years. Mean SLEDAI was 11.75±7.43.
NKT-cells absolute number (cell/mm3) was significantly decreased in SLE patients (89±135) compared to controls (287±133), (P=0.001). Likewise, the absolute number of NKT-cells (cell/mm3) was significantly lower in active SLE patients (65.2±57.8) compared to inactive ones (114.5±181.1), (P=0.001).
The expression of inhibitory KIRs was significantly lower in SLE patients (2.83±2.8%) compared to controls (5.54±2.01%) (P=0.001) While, stimulatory KIRs were significantly higher in SLE patients (3.2±3.7%) than controls (1.02±0.5%), (P=0.001). Active SLE patients showed significantly increased expression of stimulatory KIRs (5.29±4.29%) than inactive patients (1.13±0.89%), (P=0.004). However, inhibitory KIRs were significantly decreased in active (1.28±1.32%) than inactive SLE patients (4.38±3.05%), (p=0.003).
Expression of stimulatory KIRs correlated positively with ESR (r=0.3, P=0.04) and negatively with C4 (r=-0.4, P=0.01). In contrast, inhibitory KIRs correlated negatively with ESR (r=-0.5, P=0.003) and positively with C4 (r=0.4, P=0.02).
Using Receiver operating characteristic (ROC) curve analysis, expression of inhibitory KIRs on NKT-cells predicted disease activity at a cut-off value of ≤1.7% with 80% sensitivity and 80% specificity (P=0.001). While, expression of stimulatory KIRs on NKT-cells predicted active disease at a cut-off value of >1.4%, sensitivity (85%), and specificity (80%) (P=0.001).
Conclusions SLE activity is associated with an increased expression of stimulatory KIRs as well as a decreased expression of inhibitory KIRs on NKT cells. This may play a role in the pathogenesis of flares and acceleration of disease activity in SLE and could be a therapeutic target for SLE patients.
Disclosure of Interest None declared