Functional impairment of monocyte-derived dendritic cells in patients with severe chronic kidney disease

Martijn Anton Verkade1, Corné Johan van Druningen, Leonard Maria Bernardus Vaessen

  • 1Erasmus Medical Center, Department of Internal Medicine, Division of Nephrology, Bd336, Dr. Molewater plein 40, 3015 GD Rotterdam, The Netherlands.

Insights

Dendritic cell terminal differentiation is impaired in patients with severe chronic kidney disease (CKD), impacting immune responses. This dysfunction occurs regardless of haemodialysis treatment.

Area of Science:

  • Immunology
  • Nephrology
  • Cell Biology

Background:

  • Dendritic cells (DCs) are crucial antigen-presenting cells initiating immune responses.
  • Patients with chronic kidney disease (CKD), with or without chronic intermittent haemodialysis (CIHD), exhibit impaired immunity.
  • DC dysfunction is a potential cause of this immune deficit in CKD patients.

Purpose of the Study:

  • To investigate the function of monocyte-derived dendritic cells (moDC) in patients with severe CKD (GFR <30 ml/min) and those on CIHD.
  • To compare moDC function in CKD patients with age- and sex-matched healthy controls.

Main Methods:

  • In vitro analysis of monocyte-derived dendritic cells (moDC) from CKD patients and healthy controls.
  • Assessment of cell surface markers and macropinocytosis to evaluate moDC terminal differentiation.
  • Evaluation of T-cell stimulation, proliferation, and differentiation (Th1/Th2) by moDC.

Main Results:

  • Mature moDC from CKD patients showed incomplete terminal differentiation compared to controls, evidenced by cell surface markers and macropinocytosis.
  • moDC from CKD patients induced less autologous T-cell proliferation against recall antigens.
  • No significant differences were observed in allogeneic T-cell stimulation or naive T-cell differentiation into Th1/Th2 cells.

Conclusions:

  • Severe CKD impairs the terminal differentiation of monocyte-derived dendritic cells (moDC).
  • This moDC differentiation defect is consistent across different maturation stimuli.
  • The observed impairment is independent of chronic intermittent haemodialysis treatment.
Abstract

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