RESEARCH - Impaired differentiation and cytotoxicity of natural killer cells in SLE

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Arthritis Rheum. 2009 May 28;60(6):1753-1763.

Impaired differentiation and cytotoxicity of natural killer cells in

systemic lupus erythematosus.

Park YW, Kee SJ, Cho YN, Lee EH, Lee HY, Kim EM, Shin MH, Park JJ, Kim

TJ, Lee SS, Yoo DH, Kang HS.

Chonnam National University Medical School, and Chonnam National

University Hospital, Gwangju, Republic of Korea.

OBJECTIVE: 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).

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

PMID: 19479851

http://www.ncbi.nlm.nih.gov/pubmed/19479851

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