Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies

Abstract

To date, human leukocyte antigens (HLA) have been the major focus in the approach to acute and chronic antibody-mediated rejection (AMBR) in solid-organ transplantation. However, evidence from the clinic and published studies has shown that non-HLA antibodies, particularly anti-endothelial cell antibodies (AECAs), are found either in the context of AMBR or synergistically in the presence of donor-specific anti-HLA antibodies (DSA). Numerous studies have explored the influence of AECAs on clinical outcomes, yet the determination of the exact clinical relevance of non-HLA antibodies in organ transplantation is not fully established. This is due to highly heterogeneous study designs including differences in testing methods and outcome measures. Efforts to develop reliable and sensitive diagnostic non-HLA antibody tests are continuously made. This is essential considering the technical difficulties of non-HLA antibody assays and the large variation in reported incidences of antibodies. In addition, it is important to take donor specificity into account in order to draw clinically relevant conclusions from non-HLA antibody assays. Here, we provide an overview of non-HLA solid-phase and cell-based crossmatch assays for use in solid-organ transplantation that are currently available, either in a research setting or commercially.

Histocompatibility Testing: A Fundamental Aspect of Renal Transplant Workup

“…Furthermore, while antibodies against recipient grafts are commonly associated with MHC-directed responses, it is important to acknowledge that not all immune responses in transplantation are MHC-mediated. Histocompatibility testing laboratories play a crucial role in the detection of non-MHC antigens, particularly in the context of organ transplantation [49,53,54].…”

Pretransplant characteristics of kidney transplant recipients that predict posttransplant outcome

“…The pretransplant determination of HLA mismatches between recipients and donors is known for a long time in order to reduce allograft rejections. In addition, several non-HLA antibodies have been reported to cause rejection and allograft nephropathy ( 47 – 51 ). In their retrospective investigation, Lamarthée et al.…”

“…reported that higher levels of non-HLA antibodies directed against endothelial cells predicted antibody-mediated rejection histology ( 50 ). Several assays have been described to detect non-HLA antibodies ( 51 ). The importance of the genetic mismatch of non-HLA haplotypes for transplant outcome had been investigated by Reindl-Schwaighofer et al.…”

T‐cell Mediated Rejection Associated Microvascular Inflammation in the Allograft Kidney: RNAseq Analysis Using the Banff Human Organ Transplant Gene Panel

“…C4d negative, DSA negative, biopsies with interstitial inflammation, tubulitis, and MVI are being increasingly recognized [2]. This phenomenon is most often attributed to non-HLA antibody or NK cell mediated tissue injury, and this may be true in some cases [3][4][5][6]. However, in our experience, these biopsies often contain abundant T-cell infiltrates and readily demonstrable tubulitis, yet the possibility that these can primarily reflect T-cell mediated rejection (TCMR) is not often considered [7].…”