Detecting donor-specific antibodies: the importance of sorting the wheat from the chaff

Abstract

Human leukocyte antigen (HLA) compatibility is very important for successful transplantation of solid organs. In this paper, we focused on the humoral arm of immunity in the clinical setting of organ transplantation: how HLA antibodies develop, how they can be detected, and what they can do to injure organ transplants. Specifically, we explore the technical perspectives of detecting donor-specific antibodies (DSA) in HLA laboratories, and use real-life clinical cases to explain the principles. Currently there are many tools in our HLA antibody detection toolbox: conventional cytotoxicity cross match, flow cross match, and solid phase assays using beads conjugated with single or multiple HLA antigens. Single antigen bead (SAB) assay is the most sensitive tool available for detecting HLA antibodies and assessing the immunological risk for organ transplant. However, there are intrinsic limitations to solid-phase assays and they are prone to both false negativity and importantly, false positivity. Denatured antigens on single antigen beads might be the most prominent source of false positive reactivity, and may have been underestimated by many HLA experts. No single assay is perfect and therefore multiple methods, including the less sensitive assays, should be employed to determine the clinical relevance of detected HLA antibodies. Thoughtful process, including knowledge of HLA systems, cross reactivity, epitopes, and the patient's clinical history should be employed to correctly interpret data. The clinical team should work closely with HLA laboratories to ensure accurate interpretation of information and optimal management of patients before and after organ transplantation.

Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

“…No patient was weaned off immunosuppression during the study period. This study was approved by the institutional ethics review committee (Protocol #106961) and registered with www.clinicaltrials.gov (NCT03815864) DSA to the second liver transplant were determined based on a previously described method (13,14). Briefly, banked preoperative sera were screened with Luminex penal reactive antibody beads.…”

Sensitization and Desensitization in Vascularized Composite Allotransplantation

“…The exposure of the immune system to non-self HLA may result in the generation of HLA antibodies that happens the settings of transfusion, transplantation or pregnancy. The degree of polymorphism in the HLA system results in a large number of non-self stimuli for antibody development ( 7 ). In the setting of transplantation, the presence of donor-specific HLA antibodies (DSA) is well-known to be related to hyperacute rejection ( 8 ).…”

“…Treatment against AMR usually includes steroids, total plasma exchange, IVIG, plasmapheresis, bortezomib and anti-CD20 mabs ( 44 ). Both preexisting DSA but especially de-novo DSA are currently discussed as main contributors to late allograft injury and graft failure ( 7 ). The Innsbruck group reported the first case of a primarily B-cell-driven rejection episode with the development of dnDSA indicative of AMR in a patient after forearm transplantation at 9 years post-transplant, without recent trigger such as surgery or blood transfusion.…”

De Novo Donor Specific Antibody and Long-Term Outcome After Liver Transplantation: A Systematic Review and Meta-Analysis

“…It is clearly documented that developing de novo donor specific antibodies (dn-DSA) has a pathogenic role in solid organ allografts such as the kidney (3), lung (4), heart (5), pancreas (6), and intestine (7). dn-DSAs are associated with late acute antibody mediated rejection and chronic antibody-mediated rejection, which can have effects on the long survival (8)(9)(10).…”