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Complement activation during tryptophan immunoadsorption treatment

A A Alarabi1, B Nilsson, U Nilsson

  • 1Department of Internal Medicine, University Hospital, Uppsala, Sweden.

Artificial Organs
|September 1, 1993
PubMed
Summary
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This study introduces a new extracorporeal treatment to remove anti-human lymphocyte antigen (HLA) antibodies before kidney transplants. The immunoadsorption column (IM-TR) treatment activates complement, generating C3d fragments that may reduce antibody levels.

Area of Science:

  • Nephrology
  • Immunology
  • Transplantation Science

Background:

  • Antibodies against human lymphocyte antigens (HLA) pose a significant challenge in renal transplantation, often necessitating pre-transplant antibody removal.
  • Plasmapheresis is a common method for reducing these antibodies, but novel extracorporeal procedures are being explored to improve graft survival.

Purpose of the Study:

  • To evaluate a new immunoadsorption column (IM-TR) procedure for removing anti-HLA antibodies in patients awaiting renal transplantation.
  • To investigate the mechanisms underlying the reduction of antibody levels during IM-TR treatment.

Main Methods:

  • Utilized an immunoadsorption column (IM-TR) with a polyvinyl alcohol (PVA) gel matrix conjugated with tryptophan.
  • Treated 7 HLA-immunized patients with 12 IM-TR sessions (3 sessions/week) prior to renal transplantation.

Related Experiment Videos

  • Monitored immunoglobulin levels and complement activation, specifically the C3d (C3dg) fragment.

    • Main Results:

    • IM-TR treatment showed less direct immunoglobulin depletion compared to plasmapheresis.
    • Significant complement activation via the alternative pathway was observed during IM-TR treatment.
    • Exceedingly high levels of the complement activation fragment C3d (C3dg) were detected in patient plasma.

    Conclusions:

    • The reduction in antibody levels during IM-TR treatment may involve mechanisms beyond simple immunoglobulin depletion.
    • Extensive generation of C3dg is a key finding, suggesting its potential role in immune response modulation.
    • C3dg's known immunoregulatory properties indicate it may contribute to the observed decrease in anti-HLA antibody levels, potentially improving transplant outcomes.