title: Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Chonnam National University Medical School, and Chonnam National University Hospital, Gwangju, Republic of Korea. parkyw@jnu.ac.kr
authors.forename: Yong-Wook
authors.initials: YW
authors.lastname: Park
authors.forename: Seung-Jung
authors.initials: SJ
authors.lastname: Kee
authors.forename: Young-Nan
authors.initials: YN
authors.lastname: Cho
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Lee
authors.forename: Hwa-Youn
authors.initials: HY
authors.lastname: Lee
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Kim
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Shin
authors.forename: Jeong-Jin
authors.initials: JJ
authors.lastname: Park
authors.forename: Tae-Jong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Shin-Seok
authors.initials: SS
authors.lastname: Lee
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Yoo
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Kang
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology; D001528:Behcet Syndrome / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000473:pathology / Q000502:physiology; D007694:Killer Cells, Natural / Q000473:pathology* / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000473:pathology* / Q000503:physiopathology*; D008181:Lupus Nephritis / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000473:pathology / Q000503:physiopathology; D013921:Thrombocytopenia / Q000473:pathology / Q000503:physiopathology
chemical_list: D015375:Receptors, Interleukin-2; D054353:Perforin; D053804:Granzymes