title: B-cell biomarkers in transplantation--from genes to therapy.
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.
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.
authors.forename: G D
authors.initials: GD
authors.lastname: Banham
authors.forename: M R
authors.initials: MR
authors.lastname: Clatworthy
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism*; D005796:Genes; D006801:Humans; D016030:Kidney Transplantation; D008213:Lymphocyte Activation / Q000276:immunology; D059467:Transcriptome / Q000235:genetics
chemical_list: D015415:Biomarkers
keywords: B cells; genetic variation; kidney transplantation; tolerance; transcriptomics