CD56brightCD16-to CD57+CD56dimCD16+NK cell ratio discriminates disease activity and renal involvement in patients with systemic lupus erythematosus

Objective 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. Methods 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). Results 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. Conclusion 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.