High frequency of activated NKp46(+) natural killer cells in patients with new diagnosed of latent autoimmune diabetes in adults

Autoimmunity. 2015 Jun;48(4):267-73. doi: 10.3109/08916934.2014.990629. Epub 2014 Dec 12.


To determine the potential association of different subsets of NK cells with the development of latent autoimmune diabetes of adults (LADA) in patients. The frequency of different subsets of NK and NKT cells, including IFN-γ(+) and CD107a(+) NK and NKT cells, in 27 patients with newly diagnosed LADA and 20 healthy controls (HC) were determined by flow cytometry. The concentrations of serum autoantibodies against GAD65 were measured by direct radioligand assay. The potential association of the frequency of NK cells with clinical measures was analyzed. In comparison with that in the HC, significantly higher frequency of peripheral blood NK and NKp46(+) NK cells, but lower frequency of KIR3DL1(+) NK cells were detected in patients with newly diagnosed LADA (p < 0.0001, p < 0.0001, p = 0.0039, respectively). The percentages of inducible IFN-γ(+) NK cells were significantly higher in the LADA patients than that in the HC (p < 0.0001). Moreover, the percentages of NKp46(+) NK cells were negatively correlated with the levels of fasting plasma C-peptide in patients (R = -0.4877, p = 0.0099). There was no significant difference in the frequency of spontaneous and inducible CD107a(+) between patients and controls. Our data indicate a higher frequency of activated NKp46(+) NK cells may be associated with the development of LADA in humans.

Keywords: CD107a; IFN-γ; LADA; NK cells; NKT cells.

MeSH terms

  • Adult
  • Antigens, Surface / metabolism
  • C-Peptide / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / immunology*
  • Lymphocyte Count*
  • Male
  • Middle Aged
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism


  • Antigens, Surface
  • C-Peptide
  • NCR1 protein, human
  • Natural Cytotoxicity Triggering Receptor 1
  • Interferon-gamma