Importance of human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes in liver transplantation

Abstract

Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance, which is described by eventual imbalances or deregulation in the balance of cytokines, mediators, effectors, and regulatory cells in the complex milieu of the liver. In this section, we will comment on the importance of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor (KIR) genotypes in the evolution of liver transplantation. Thus, HLA compatibility, viral infections, and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival. There have been reports of increased risk of acute and chronic rejection with ductopenia, faster graft fibrosis, biliary problems, poorer survival, and even de novo autoimmune hepatitis when DSAs are present in the recipient. Higher mean fluorescence intensity (MFI) values of the DSAs and smaller graft size were associated with poorer patient outcomes, implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods, according to the investigators. Similarly, in a combined kidney-liver transplant, a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment. The renal graft was lost owing to antibody-mediated rejection (AMR). The HLA antigens expressed by the transplanted liver graft influenced antibody elimination. Pathologists are increasingly diagnosing AMR in liver transplants, and desensitization therapy has even been employed in situations of AMR, particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex. In conclusion, after revealing the negative impacts of DSAs with high MFI, pretransplant virtual crossmatch techniques may be appropriate to improve evolution; however, they may extend cold ischemia periods by requiring the donor to be typed.

Keywords: Acute rejection; Alloantibodies donor-specific antibodies-donor-specific anti-human leukocyte antigen antibodies; Chronic rejection; Human leukocyte antigen matching; Killer-cell immunoglobulin-like receptor matching; Liver transplant.

Figure 1

Potential associations of donor-specific anti-human leukocyte antigen antibodies and human leukocyte antigen and/or matching with the evolution of liver transplantation. AMR: Antibody-mediated rejection; HCV: Hepatitis C virus; HLA: Human leukocyte antigen; KIR: Killer-cell immunoglobulin-like receptor.