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 failur...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.展开更多
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 H...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.展开更多
文摘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.
文摘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.
