Increased TIM-3 + PD-1 + NK cells are associated with the disease activity and severity of systemic lupus erythematosus

It is well established that natural killer (NK) cells are dysregulated in systemic lupus erythematosus (SLE) patients. However, the functions of NK cells and the mechanisms regulated by them in SLE remain incompletely understood. Patients with SLE were recruited from The First Affiliated Hospital of Nanchang University, and their clinical characteristics and treatments were recorded. The expression levels of T cell immunoglobulin mucin-3 (TIM-3) and programmed cell death protein 1 (PD-1) on NK cells were examined using flow cytometry. The correlations between the increase in TIM-3 + PD-1 + NK cells in the SLE patients and clinical traits, including inflammatory markers, auto-antibodies, disease activity and severity of SLE, were examined. The TIM-3 + NK cells, PD-1 + NK cells and TIM-3 + PD-1 + NK cells were significantly increased in the SLE patients. The increase in TIM-3 + PD-1 + NK cells in the patients with SLE was associated with erythrocyte sedimentation rate, C-reactive protein, anti-double stranded DNA, anti-ribosomal P, SLE disease activity index and clinical features. The frequency of TIM-3 + PD-1 + NK cells in SLE patients with a cardiovascular disease (CVD) was significantly lower than that in SLE patients without a CVD. Moreover, the increased TIM-3 + PD-1 + NK cells were significantly decreased in SLE patients following treatment. The present study suggested that the increased TIM-3 + PD-1 + NK cells were associated with the disease activity and severity of SLE and may play a role in SLE pathogenesis.