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

Silver, Christina LU ; Uvebrant, K ; Oderup, Cecilia LU ; Lynch, Kristian LU ; Harris, R A ; Lernmark, Åke LU orcid ; Agardh, Carl-David LU and Cilio, Corrado LU (2010) In Clinical and Experimental Immunology May 4. p.48-56
Abstract
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... (More)
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. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Experimental Immunology
volume
May 4
pages
48 - 56
publisher
Oxford University Press
external identifiers
  • wos:000278396900007
  • pmid:20408863
  • scopus:77953280169
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2010.04114.x
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Unit on Vascular Diabetic Complications (013241510), Diabetes and Celiac Unit (013241540), Cellular Autoimmunity Unit (013241520)
id
0f5969b2-35ad-461e-ab4d-49c62bd5b5ed (old id 1594950)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20408863?dopt=Abstract
date added to LUP
2016-04-04 08:53:02
date last changed
2025-04-04 14:20:19
@article{0f5969b2-35ad-461e-ab4d-49c62bd5b5ed,
  abstract     = {{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 &lt; 0.0001), whereas killer cell immunoglobulin-like receptor (KIR)3DL1 expression was decreased (P &lt; 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.}},
  author       = {{Silver, Christina and Uvebrant, K and Oderup, Cecilia and Lynch, Kristian and Harris, R A and Lernmark, Åke and Agardh, Carl-David and Cilio, Corrado}},
  issn         = {{0009-9104}},
  language     = {{eng}},
  pages        = {{48--56}},
  publisher    = {{Oxford University Press}},
  series       = {{Clinical and Experimental Immunology}},
  title        = {{Altered natural killer (NK) cell frequency and phenotype in latent autoimmune diabetes in adults (LADA) prior to insulin deficiency.}},
  url          = {{http://dx.doi.org/10.1111/j.1365-2249.2010.04114.x}},
  doi          = {{10.1111/j.1365-2249.2010.04114.x}},
  volume       = {{May 4}},
  year         = {{2010}},
}