Humoral theory of transplantation: some hot topics

Br Med Bull. 2013:105:139-55. doi: 10.1093/bmb/lds037. Epub 2013 Feb 7.

Abstract

Introduction: Antibody is a major cause of allograft injury. However, it has not been routinely tested post-transplant.

Sources of data: A literature search was performed using PubMed on the topics of 'antibody monitoring', 'autoantibody and allograft dysfunction' and 'prevention and treatment of antibody-mediated rejection (AMR)'.

Areas of agreement: Donor-specific antibody (DSA) monitoring not only helps to identify patients at risk of AMR, but also serves as a biomarker to personalize patient's maintenance immunosuppression. Development of autoantibody is a secondary response following primary tissue injury. Some autoantibodies are directly involved in allograft injury, while others only serve as biomarkers of tissue injury.

Areas of controversy: It remains controversial whether DSA-positive patients without symptoms need to be treated. In addition, given the variation in study designs and patient's characteristics, there is discrepancy regarding which treatment regimens provide optimal clinical outcome in preventing/treating AMR.

Growing points: Efficacy of B-cell and/or antibody-targeted therapies in treating or preventing AMR would be better measured by the incorporation of antibody monitoring into current functional and pathological assays.

Areas timely for developing research: Research in B-cell targeted therapies to prevent and treat AMR is rapidly growing, which includes monoclonal antibodies against B-cell markers CD20, CD40, CD19, BlyS, etc. It requires extensive clinical research to determine the best approach to inhibit or delete antibody and how to balance the drug efficacy with safety.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies / immunology*
  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Autoantibodies / immunology
  • Boronic Acids
  • Bortezomib
  • Complement C4b
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control
  • Humans
  • Isoantibodies / immunology
  • Peptide Fragments
  • Pyrazines
  • Rituximab
  • Transplantation / adverse effects*

Substances

  • Antibodies
  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Autoantibodies
  • Boronic Acids
  • Isoantibodies
  • Peptide Fragments
  • Pyrazines
  • Rituximab
  • blinatumomab
  • Bortezomib
  • belimumab
  • Complement C4b
  • complement C4d
  • eculizumab
  • dacetuzumab