Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes

Clin Exp Immunol. 2019 Jul;197(1):64-73. doi: 10.1111/cei.13289. Epub 2019 Mar 24.


There is currently scarce knowledge of the immunological profile of patients with latent autoimmune diabetes mellitus in the adult (LADA) when compared with healthy controls (HC) and patients with classical type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective of this study was to investigate the cellular immunological profile of LADA patients and compare to HC and patients with T1D and T2D. All patients and age-matched HC were recruited from Uppsala County. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine the proportions of immune cells by flow cytometry. Plasma concentrations of the cytokine interleukin (IL)-35 were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD11c+ CD123- antigen-presenting cells (APCs) was lower, while the proportions of CD11c+ CD123+ APCs and IL-35+ tolerogenic APCs were higher in LADA patients than in T1D patients. The proportion of CD3- CD56high CD16+ natural killer (NK) cells was higher in LADA patients than in both HC and T2D patients. The frequency of IL-35+ regulatory T cells and plasma IL-35 concentrations in LADA patients were similar to those in T1D and T2D patients, but lower than in HC. The proportion of regulatory B cells in LADA patients was higher than in healthy controls, T1D and T2D patients, and the frequency of IL-35+ regulatory B cells was higher than in T1D patients. LADA presents a mixed cellular immunological pattern with features overlapping with both T1D and T2D.

Keywords: Cellular immunology; IL-35; LADA; type 1 diabetes; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adult
  • Aged
  • Antigen-Presenting Cells / classification
  • Antigen-Presenting Cells / immunology
  • B-Lymphocytes, Regulatory / immunology
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 2 / immunology
  • Female
  • Humans
  • Immunity, Cellular*
  • Immunity, Innate
  • Interleukins / blood
  • Killer Cells, Natural / immunology
  • Latent Autoimmune Diabetes in Adults / immunology*
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology


  • Interleukins
  • interleukin-35, human