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Activation status of CD56dim natural killer cells is associated with disease activity of patients with systemic lupus erythematosus

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Abstract

Objectives

Decreased natural killer (NK) cells have been reported in systemic lupus erythematosus (SLE) patients. However, the role of NK cells in the pathogenesis of SLE is not well understood. In this study, we aimed to characterize NK cell subsets, phenotypes, and cytokine-secreting functions and investigate the clinical relevance of NK cells in SLE patients.

Methods

Peripheral blood samples from 81 SLE patients and 59 healthy donors (HDs) were collected. The frequency and phenotype of NK cells were measured by flow cytometry. Intracellular interferon-γ (IFN-γ) production by NK cells was evaluated by flow cytometry after stimulation with interleukin-12 (IL-12) and IL-18.

Results

The percentages of NK cells in the peripheral blood of SLE patients were significantly lower than those in HDs, and the percentages of CD56dim NK cells among total NK cells showed a trend toward decrease. The CD56dim NK cells in SLE patients showed increased production of IFN-γ and displayed relatively activated phenotypic characteristics, including significant increases in NKp44, NKp46, and CD69 and decreased expression of CD16 and CD158a/h/g. Furthermore, CD56dim NK cells in active SLE patients had higher percentages of NKp44+ cells and lower percentages of CD158a/h/g+ cells than those in inactive SLE patients. The percentages of CD158a/h/g+ cells among CD56dim NK cells were negatively correlated with the systemic lupus erythematosus disease activity index (SLEDAI) and positively correlated with C3 and C4 levels.

Conclusion

CD56dim NK cells in SLE patients show a reduced proportion tendency among total NK cells and are activated, which partially reflects the disease activity. CD158a/h/g expression on CD56dim NK cells may be considered an index of disease activity.

Key Points

• In patients with SLE, the proportion of CD56dim NK cells showed a decreased trend and CD56dim NK cells were phenotypically activated which partially reflects the disease activity.

• CD158a/h/g expression on CD56dim NK cells were decreased which may be used as an indicator for evaluating disease activity in SLE patients.

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Acknowledgments

This research was supported by the grants from the National Natural Science Foundation of China (31470854) and the Pujiang Talents Plan (16PJ1405600).

Funding

National Natural Science Foundation of China (Grants No. 31470854) and Pujiang Talents Plan (Grants No. 16PJ1405600).

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Authors and Affiliations

  1. Department of Renal and Rheumatology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China

    Manman Liu, Xiaoyan Zhang, Gengru Jiang & Xinfang Huang

  2. Department of Rheumatology and Immunology, Nanjing Jiangning Hospital, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 211100, China

    Manman Liu

  3. The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China

    Junli Liu & Yichuan Xiao

  4. Department of Rheumatology, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China

    Xinfang Huang

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  1. Manman Liu
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Correspondence to Xinfang Huang.

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Figure S1

Frequency of CD56dim NK cells in SLE patients before and after treatment or follow-up. (a) Flow cytometry gating strategy for the analysis of NK cells. (b) SLEDAI scores, frequency of total NK cells among lymphocytes and percentages of CD56bright NK cells and CD56dim NK cells among total NK cells from six SLE patients were determined at two points during induction therapy or follow-up (Wilcoxon signed rank test). The first and second measurements are depicted. Data from the same patient before and after treatment or follow-up are denoted by an individual line. (PNG 197 kb).

High-resolution image (EPS 21905 kb).

Figure S2

IFN-γ production by CD56dim NK cells from SLE patients not taking (n = 22) and taking HCQ (n = 25) with IL12/18 stimulation (unpaired t test) (PNG 11 kb).

High-resolution image (EPS 810 kb).

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Liu, M., Liu, J., Zhang, X. et al. Activation status of CD56dim natural killer cells is associated with disease activity of patients with systemic lupus erythematosus. Clin Rheumatol 40, 1103–1112 (2021). https://doi.org/10.1007/s10067-020-05306-x

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  • DOI: https://doi.org/10.1007/s10067-020-05306-x

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