Mechanisms of organ transplant injury mediated by B cells and antibodies: Implications for antibody-mediated rejection

Abstract

Am J Transplant. 2020;20:23-32. | 23 amjtransplant.com 1 | INTRODUC TI ON Under current standard of care, the median graft survival for first kidney allografts from deceased donors in the United States from 2008 to 2015 (https://optn.trans plant.hrsa.gov/data/view-data-repor ts/natio nal-data/) is 93.2% at 1-year posttransplant but declines to 74.4% at 5 years posttransplant. Comparable graft survival rates are reported for heart and liver transplantation, whereas the survival rates for lung and small bowel transplants are considerably lower. Chronic antibody-mediated rejection (ABMR) has emerged as a leading cause of graft loss for kidney transplants, although other mechanisms including T cell-mediated rejection (TCMR), infections, and immunosuppression-related drug toxicity have also been implicated. 1-3 Chronic ABMR appears to be less responsive to current

Treatment of antibody‐mediated rejection with double‐filtration plasmapheresis, low dose IVIg plus rituximab after kidney transplantation

“…Compared to acute antibody‐mediated rejection (ABMR), chronic ABMR is associated with slower increases in DSAs, which may be high or low titer and transient or persistent. These DSAs elicit cycles of injury and repair that manifest as multi‐lamination of the peritubular capillary basement membrane or arteriopathy manifesting as intimal fibrosis 7 . A kidney‐allograft biopsy is then mandatory to ascertain a diagnosis of chronic ABMR; thus, the XV Banff meeting clarified details of kidney‐transplant pathology and refinements to the criteria for chronic active T cell‐mediated, borderline, and antibody‐mediated rejection 8 …”

Regulatory B cells: TIM‐1, transplant tolerance, and rejection

“…Antibodies targeting the allograft can significantly impact allograft survival by mediating an acute form of rejection (antibody-mediated rejection) and contributing to chronic allograft rejection. 67 , 68 With the advent of Rituximab (humanized anti-CD20), attempts were made to reduce antibody-mediated components of rejection by pre-emptively depleting B cells in the peri-transplant period. Surprisingly, this led to a marked increase in acute T cell–mediated rejection (83%) in kidney transplant patients within the first three months post-transplantation.…”

Current Desensitization Strategies in Heart Transplantation

“…Figure 1 provides a schematic overview along with the most common current approaches to desensitization based on a recent international survey ( 4 ). The primary and recall humoral response are detailed in several recent reviews and summarized below ( 13 , 18 , 19 ). Alloreactive T cells and innate immunity will also be briefly considered.…”

“…At this stage, B cells can either directly differentiate in an extrafollicular manner or enter the germinal center. Extrafollicular B cells can differentiate into antibody secreting cells (ASCs) or acquire a memory phenotype ( 13 ). Alternatively, B cells can enter the germinal center (GC) which marks another critical collaboration between T and B cells ultimately resulting in selection and clonal proliferation of B cells with a high affinity B cell receptor (BCR).…”

“…Overview of the Immune Response to Foreign HLA Exposure to foreign HLA can initiate a complex set of immune reactions which may result in a short-term 'effector response', long-lived plasma cells (LLPCs) capable of sustained antibody secretion over decades, and/or the establishment of B and T cell memory [reviewed in (13)]. As a result, HLA allosensitization may either be overt (detectable HLA antibodies) or cryptic (the presence of cellular memory in the absence of detectable HLA antibodies).…”