Unraveling the Role of Allo-Antibodies and Transplant Injury

Abstract

Alloimmunity driving rejection in the context of solid organ transplantation can be grossly divided into mechanisms predominantly driven by either T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), though the co-existence of both types of rejections can be seen in a variable number of sampled grafts. Acute TCMR can generally be well controlled by the establishment of effective immunosuppression (1, 2). Acute ABMR is a low frequency finding in the current era of blood group and HLA donor/recipient matching and the avoidance of engraftment in the context of high-titer, preformed donor-specific antibodies. However, chronic ABMR remains a major complication resulting in the untimely loss of transplanted organs (3–10). The close relationship between donor-specific antibodies and ABMR has been revealed by the highly sensitive detection of human leukocyte antigen (HLA) antibodies (7, 11–15). Injury to transplanted organs by activation of humoral immune reaction in the context of HLA identical transplants and the absence of donor specific antibodies (17–24), strongly suggest the participation of non-HLA (nHLA) antibodies in ABMR (25). In this review, we discuss the genesis of ABMR in the context of HLA and nHLA antibodies and summarize strategies for ABMR management.

Impact of Immunoglobulin M-Type Donor-Specific Human Leukocyte Antigen–Antibody Levels in Supernatants from Cultured Peripheral Blood Mononuclear Cells as Predictors of Antibody-Mediated Rejection

“…Furthermore, the chronic use of immunosuppressive agents to repress T-cell proliferation may not significantly inhibit PC survival, because PCs may survive in a T cell-independent manner [ 7 ]. More recently, efficient immunosuppressive therapies have been considered necessary in inhibiting PC growth and survival; however, such interventions are, in general, accompanied by severe side effects, such as pancytopenia, anemia, and viral infection [ 8 , 9 ]. Thus, the early detection of DSA-secreting mBCs may allow for timely intervention for AMR control [ 10 , 11 ].…”

Adipose-derived stromal cells modulating composite allotransplant survival is correlated with B cell regulation in a rodent hind-limb allotransplantation model

“…However, B cells also contribute to transplantation rejection through their ability to present antigens, secrete pro-inflammatory cytokines, and produce antibodies [20,21,26]. The production of donor-specific antibodies (DSAs) against donor human leukocyte antigen (HLA) is the primary cause of developing antibody-mediated rejection (AMR) [20,26]. After transplantation, DSAs target donor endothelial cells, and then trigger immune responses and classical complement cascade which causes the deposition of C4d, leading to allograft damage and loss [20].…”

“…In the post solid organ transplantation context, B cells mediate humoral rejection by producing HLAs and DSAs while also providing costimulatory signals to T cells. The complement system, a component of the innate immune system [26], has also been demonstrated to modulate adaptive immunity and bridge the innate Four randomly selected areas were then photographed at × 400 magnification. Images were captured and analyzed with Image-Pro Plus image analysis software.…”

Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome

“…Our study has limitations. First, it is observational and consequently does not provide complete information about the damaging pathways caused by anti-HLA antibodies, given the close relationship between preformed DSA and AMR revealed in different organ transplants by histopathological findings and functional manifestations ( 47 ). Since diagnostic criteria for allograft rejection varied over the time course of the study, the association between AMR and the C1q-binding ability could not be accurately ascertained.…”