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Altered natural killer (NK) cell frequency and phenotype in latent autoimmune diabetes in adults (LADA) prior to insulin deficiency.

Author:
  • Christina Silver
  • K Uvebrant
  • Cecilia Oderup
  • Kristian Lynch
  • R A Harris
  • Åke Lernmark
  • Carl-David Agardh
  • Corrado Cilio
Publishing year: 2010
Language: English
Pages: 48-56
Publication/Series: Clinical and Experimental Immunology
Volume: May 4
Document type: Journal article
Publisher: British Society for Immunology

Abstract english

Summary Approximately 10% of the patients diagnosed with type 2 diabetes (T2D) have detectable serum levels of glutamic acid decarboxylase 65 autoantibodies (GADA). These patients usually progress to insulin dependency within a few years, and are classified as being latent autoimmune diabetes in adults (LADA). A decrease in the frequency of peripheral blood natural killer (NK) cells has been reported recently in recent-onset T1D and in high-risk individuals prior to the clinical onset. As NK cells in LADA patients have been investigated scarcely, the aim of this study was to use multicolour flow cytometry to define possible deficiencies or abnormalities in the frequency or activation state of NK cells in LADA patients prior to insulin dependency. All patients were GADA-positive and metabolically compensated, but none were insulin-dependent at the time blood samples were taken. LADA patients exhibited a significant decrease in NK cell frequency in peripheral blood compared to healthy individuals (P = 0.0018), as reported previously for recent-onset T1D patients. Interestingly, NKG2D expression was increased significantly (P < 0.0001), whereas killer cell immunoglobulin-like receptor (KIR)3DL1 expression was decreased (P < 0.0001) within the NK cell population. These observations highlight a defect in both frequency and activation status of NK cells in LADA patients and suggest that this immunological alteration may contribute to the development of autoimmune diabetes by affecting peripheral tolerance. Indeed, recent evidence has demonstrated a regulatory function for NK cells in autoimmunity. Moreover, the decrease in NK cell number concords with observations obtained in recent-onset T1D, implying that similar immunological dysfunctions may contribute to the progression of both LADA and T1D.

Keywords

  • Immunology in the medical area

Other

Published
  • Diabetes - Cellular Autoimmunity
  • Diabetes and Celiac Unit
  • ISSN: 0009-9104
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00