B-cell biomarkers in transplantation - from genes to therapy

Research output: Contribution to journalReview articlepeer-review

Authors

Colleges, School and Institutes

Abstract

An increased understanding of the mechanisms by which the immune system mounts a response to transplanted organs has allowed the development of immunosuppressive regimens that limit acute T-cell-mediated rejection (TCMR). However, the treatment of acute and chronic antibody-mediated rejection (ABMR) in kidney transplants remains sub-optimal. The occurrence and severity of antibody-mediated graft pathology are variable, and genetic polymorphisms that affect the magnitude and nature of the B-cell response, as well as effector functions of antibody, are likely to contribute to such phenotypic variation. Here we review current efforts to understand and quantify the contribution of B cells to renal transplant pathology by studying variation in DNA, mRNA and proteins. Large genetic studies with information on B-cell-specific genetic variants are scarce. At a transcriptomic level, there is evidence that B cells are essential contributors to transplant tolerance and may protect against TCMR and ABMR. In contrast, at the protein level, the detection of donor-specific human leukocyte antigen (HLA) antibodies and an assessment of their capacity to bind complement allow patients of high immunological risk to be identified. Other biomarkers, such as serum B-cell-activating factor (BAFF) or interleukin (IL)-10-producing B cells, may allow this risk stratification to be refined. An increased understanding of the significance of these biomarkers should allow a more accurate assessment of how an individual patient's B cells will impact allograft responses and thereby allow clinicians to adjust therapeutic strategies appropriately.

Bibliographic note

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Details

Original languageEnglish
Pages (from-to)82-92
Number of pages11
JournalTissue Antigens
Volume85
Issue number2
Early online date28 Jan 2015
Publication statusPublished - Feb 2015

Keywords

  • Animals, B-Lymphocytes/immunology, Biomarkers/metabolism, Genes, Humans, Kidney Transplantation, Lymphocyte Activation/immunology, Transcriptome/genetics, B cells, transcriptomics, genetic variation, tolerance