Altered CD46-mediated T cell co-stimulation in haemodialysis patients

Authors

  • P.-T. Brinkkoetter,

    Corresponding author
    1. V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany
      Dr Paul-Thomas Brinkkoetter, V. Medizinische Universitätsklinik, Klinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany.
      E-mail: paul.brinkkoetter@med5.ma.uni-heidelberg.de
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    • *

      P. T. B and S. M. contributed equally to this work.

  • S. Marinaki,

    1. V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany
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    • *

      P. T. B and S. M. contributed equally to this work.

  • U. Gottmann,

    1. V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany
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  • S. Fleckenstein,

    1. V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany
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  • C. Stump,

    1. V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany
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  • F. J. Van Der Woude,

    1. V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany
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  • C. Braun,

    1. V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany
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  • B. A. Yard

    1. V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany
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Dr Paul-Thomas Brinkkoetter, V. Medizinische Universitätsklinik, Klinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany.
E-mail: paul.brinkkoetter@med5.ma.uni-heidelberg.de

Summary

While most of our understanding of immune dysfunction in dialysis patients involves alterations in CD28–CD80/86 signalling, nothing is known of CD46-mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to CD46 and complement activation occurs during haemodialysis (HD), we addressed whether CD46-mediated T cell activation is altered in HD (n = 9), peritoneal dialysis (PD) (n = 10) and predialysis patients (n = 8) compared to healthy controls (HC) (n = 8). T cell surface markers, T cell proliferation and interleukin (IL)-10 production were studied in CD4+T cells. In addition, CD46 splice-variants and IL-10 promoter gene polymorphisms were studied by reverse transcription (RT) or amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), respectively. In all uraemic patients, irrespective of the stage of renal insufficiency or dialysis modality, a significant increase in the percentage of CD25 positivity in naive CD4+T cells was found (64% ± 21%versus 23% ± 18%, P < 0·001). Lymphocytes of HD patients proliferated in greater numbers and produced more IL-10 after co-stimulation with anti-CD46 than after co-stimulation with anti-CD28. This was also found in CD4+T cells of PD patients, albeit to a lesser extent. In contrast, with T cells of predialysis patients and of HC, co-stimulation via CD28 was more efficient. The observed alterations in T cell proliferation and IL-10 production were associated neither with CD46 splice variants nor with IL-10 promoter gene polymorphisms. Lymphocytes of HD patients show an increased response on CD46 co-stimulation. These data suggest that ongoing complement activation in HD patients may lead to alterations in acquired immunity.

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