Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation

Abstract

Donor human leukocyte antigen (HLA)-specific antibodies (DSA) play an important role in solid organ transplantation. Preexisting IgG isotype DSA are considered a risk factor for antibody mediated rejection, graft failure or graft loss. The post-transplant development of DSA depends on multiple factors including immunogenicity of mismatched antigens, HLA class II typing of the recipient, cytokine gene polymorphisms, and cellular immunoregulatory mechanisms. De novo developed antibodies require special attention because not all DSA have equal clinical significance. Therefore, it is important for transplant clinicians and transplant immunologists to accurately characterize DSA. In this review, the contemporary immunological techniques for detection and characterization of anti-HLA antibodies and their pitfalls are described.

Keywords: Human leukocyte antigen, Transplantation, Antibodies, Solid phase analysis, Flow cytometry

Core tip: In solid organ transplantations the graft outcomes critically depend on the degree of human leukocyte antigen (HLA) matching between the donor and recipient. Although the cellular component of the allogeneic immune response to the transplanted tissue plays a key role, the contribution of antibodies should not be underestimated. The detection of anti-HLA class I and class II antibodies is an important component of the initial work-up of a potential transplant candidate. The introduction of new highly sensitive technologies such as solid-phase based technologies has had a tremendous effect on organ allocation and immunomodulation strategies.