Clinical implications of anti-HLA antibodies testing in kidney transplantation

Alloantibodies against donor human leukocyte antigens (HLA), termed as donor‑specific antibodies (DSA), are one of the most important factors for both early and late kidney allograft dysfunction. In the past, these antibodies were mainly detected through cell‑based crossmatch tests. Recently, new techniques such as solid phase immunoassays (SPI) have revealed these antibodies in patient sera with a high degree of detail, previously unimaginable. They have allowed us to accurately determine recipients’ allosensitization status, improve pre‑transplant risk assessment with a potential donor and post‑transplant alloimmune monitoring. However, the high sensitivity of these new assays has also created areas of uncertainty about their clinical impact. In the pre‑transplant setting, the presence of preformed DSA has been associated with an increased risk of antibody‑mediated rejection (AMR) and subsequent allograft loss. Nevertheless, several studies have shown that not all DSA are deleterious. Hence, understanding the clinical correlations of DSA characteristics, namely strength, HLA class, complement‑fixing ability or IgG subclasses, is paramount for an adequate stratification of the immunological risk at transplant. Furthermore, given that the number of allosensitized patients on waiting lists is increasing, the added information from these new SPI is essential to improve their chance of being transplanted with an admissible immunological risk. After transplantation, the appearance of de novo DSA (dnDSA) has also been associated with a deleterious effect on kidney allograft survival. Moreover, it has been acknowledged that a majority of late allograft failures are caused by alloantibody‑driven injury. The current challenges, in this setting, are determining cost‑effective DSA screening protocols and understanding which patients could benefit from specific interventions. Furthermore, although therapeutic strategies to control antibody‑induced damage remain limited, the longitudinal surveillance of dnDSA emergence and the clinical correlations of their characteristics will play a crucial role in the improvement of late kidney allograft survival.