Systemic Lupus Erythematosus Basic Science Studies
Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus
Article first published online: 28 MAY 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 6, pages 1753–1763, June 2009
How to Cite
Park, Y.-W., Kee, S.-J., Cho, Y.-N., Lee, E.-H., Lee, H.-Y., Kim, E.-M., Shin, M.-H., Park, J.-J., Kim, T.-J., Lee, S.-S., Yoo, D.-H. and Kang, H.-S. (2009), Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus. Arthritis & Rheumatism, 60: 1753–1763. doi: 10.1002/art.24556
- Issue published online: 28 MAY 2009
- Article first published online: 28 MAY 2009
- Manuscript Accepted: 2 MAR 2009
- Manuscript Received: 26 JUN 2008
- Korea Research Foundation. Grant Number: KRF-2007-521-E00061
- Korean government (MOEHRD)
- Chonnam National University Hospital Research Institute of Clinical Medicine. Grant Number: CRI08036-1
- Korea Engineering Foundation
- Research Center for Women's Diseases. Grant Number: R11-2005-017-02002
To determine the cytotoxicity of natural killer (NK) cells and the level of differentiation of hematopoietic stem cells (HSCs) into NK cells in systemic lupus erythematosus (SLE).
Patients with SLE (n = 108), rheumatoid arthritis (RA; n = 90), Behçet's disease (n = 39), or ankylosing spondylitis (n = 41) and healthy control subjects (n = 173) were enrolled in the study. NK cell levels, NK cell cytotoxicities, and lymphokine-activated killer (LAK) activities against K562 cells were measured by flow cytometry. Gene expression was assessed by reverse transcription–polymerase chain reaction. NK cells were differentiated from peripheral blood and bone marrow HSCs in vitro.
Percentages and absolute numbers of NK cells, cytotoxicities, and LAK activities were significantly lower in the peripheral blood of SLE and RA patients than in that of healthy controls. In particular, this NK cell deficiency was more prominent in patients with lupus nephritis and those with thrombocytopenia. Notably, purified NK cells derived from SLE patients, but not RA patients, were found to have lower cytotoxicities and LAK activities than those from healthy controls. This defect of NK cells in SLE patients was found to be related to lower numbers of NK precursors and to the down-regulation of perforin and granzyme in NK cells. The proliferative capacity of HSCs, the percentages of NK cells differentiated from HSCs, and NK cell cytotoxicities were significantly lower in SLE patients.
In SLE patients, circulating levels of NK cells were diminished and their cytotoxicities were impaired. Furthermore, the differentiation of HSCs into NK cells was found to be defective. These abnormalities possibly contribute to immune system dysregulation in SLE.