School of Medicine, Southeast University, Nanjing; Department of Rheumatology and Immunology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian; and Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Clin Exp Rheumatol. 2023 Sep;41(9):1768-1776. doi: 10.55563/clinexprheumatol/o6bjl8. Epub 2023 Feb 11.
We aimed to discriminate subpopulations of peripheral natural killer (NK) cells of patients with systemic lupus erythematosus (SLE) and evaluate their usability in monitoring disease activity.
The total number of NK cells and their subpopulations were determined by flow cytometry in 68 patients with SLE and 35 healthy controls. Clinical data were extracted from medical records, including serum anti-double-stranded-DNA (anti-dsDNA), complement C3 and C4, and urine protein. Disease activity in patients with SLE was assessed using the SLE Disease Activity Index-2000 (SLEDAI-2K).
The percentages and absolute numbers of NK cells decreased, and the proportions of three major NK cell subsets defined by cell maturation status altered in SLE patients. The frequency of CD56brightCD16- NK (immature, Im NK) cells increased, while that of the CD57+CD56dimCD16- subset (mature, more differentiated, MD NK) decreased in patients with high-activity SLE, resulting in a significant increase in the Im NK-to-MD NK ratio as compared with that in patients with low-activity SLE. The area under the receiver operating characteristic curve indicated that the ratio was 0.722 in severe SLE and 0.773 in lupus nephritis, with optimal cut-off levels of 0.075 and 0.108, respectively. The ratio correlated positively with the SLEDAI-2K score, proteinuria, and serum anti-dsDNA antibody levels but negatively with C3 and C4 levels.
Our data indicate that the imbalance in Im NK and MD NK cells may play a role in lupus development and serve as a predictive biomarker to assess disease activity and renal involvement in patients with SLE.
我们旨在区分系统性红斑狼疮（SLE）患者外周自然杀伤（NK）细胞亚群，并评估其在监测疾病活动中的可用性。
通过流式细胞术检测 68 例 SLE 患者和 35 例健康对照者的 NK 细胞总数及其亚群。从病历中提取临床数据，包括血清抗双链 DNA（抗 dsDNA）、补体 C3 和 C4 以及尿蛋白。采用 SLE 疾病活动指数-2000（SLEDAI-2K）评估 SLE 患者的疾病活动度。
NK 细胞的百分比和绝对数减少，细胞成熟状态定义的三个主要 NK 细胞亚群的比例在 SLE 患者中发生改变。高活性 SLE 患者中 CD56brightCD16-NK（幼稚、ImNK）细胞的频率增加，而 CD57+CD56dimCD16-亚群（成熟、更多分化、MD NK）的频率降低，导致 ImNK 与 MD NK 比值显著升高与低活性 SLE 患者相比。受试者工作特征曲线下面积表明，该比值在严重 SLE 中为 0.722，在狼疮肾炎中为 0.773，最佳截断值分别为 0.075 和 0.108。该比值与 SLEDAI-2K 评分、蛋白尿和血清抗 dsDNA 抗体水平呈正相关，与 C3 和 C4 水平呈负相关。
我们的数据表明，ImNK 和 MDNK 细胞的失衡可能在狼疮发病机制中起作用，并可作为评估 SLE 患者疾病活动度和肾脏受累的预测生物标志物。
