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The speciality of Histocompatibility and Immunogenetics (H&I) arose to develop assays for HLA typing and HLA antibody identification in addition to crossmatching to determine the risk of transplantation between a particular recipient and donor. These assays are central to supporting patient work up for transplantation and facilitating effective use of donated organs.
In the UK there is a network of 24 H&I laboratories supporting both solid organ and haematopoietic stem cell transplantation. In kidney transplantation, patients are referred for transplant waiting list assessment and their HLA type and HLA antibody status is assessed. This information is required before a patient can be activated on the national transplant waiting list. Patients may develop HLA antibodies as a result of previous pregnancy, blood transfusion or transplant and establishing an accurate HLA antibody profile is essential to maximise a patients transplant opportunities.
HLA typing was initially performed using serological techniques, however these assays had major limitations due to the need for viable lymphocytes. The advent of molecular DNA based techniques revolutionized HLA typing.
For many years the complement dependent cytotoxicity (CDC) assay was used for HLA antibody detection and identification. Patient sera were incubated with a panel of known HLA typed cells covering the majority of known HLA antigens allowing the presence of HLA antibodies to be determined. However, the advent of Luminex® based solid phase assays in the 1990’s revolutionised HLA antibody detection and identification. They allowed rapid and accurate screening of large numbers of sera for HLA class I & II antibodies.
The aim of crossmatching is to replicate in the laboratory what would happen if a transplant took place. A crossmatch is required to assess histocompatibility between a prospective donor and recipient.
The CDC assay, first reported in 1964 by the American scientist, Paul Terasaki, and his co-workers became the platform for testing donor and recipient compatibility in most H &I laboratories around the world. Donor lymphocytes are incubated with recipient sera and if the recipient sera contained antibodies directed against donor HLA mismatches, there is cell lysis, a positive crossmatch. The introduction of the CDC assay pre-transplant was fundamental in limiting the risk of hyperacute graft rejection due to donor specific HLA antibodies.
An important refinement was the flow cytometric crossmatch assay described in 1983 by Bernie Carpenter and co-workers in Boston, USA . at the Bigham and Women’s to further facilitate assessment of patient donor compatibility in kidney transplantation. The flow cytometry crossmatch had increased sensitivity compared to the original CDC assay, and became the norm in H&I labs.
Craig Taylor’s group in Cambridge published a 10-year experience of selective omission of the pre-transplant crossmatch in deceased donor transplantation (Taylor CJ et al. Transplantation 2000; 69(5):719-23). The concept was that patient and donor compatibility could be assessed by donor HLA type and recipient HLA antibody history using stored sera (‘virtual crossmatch’), obviating the necessity for an urgent cross match immediately before deceased donor transplantation, and thus minimising cold ischaemia times, and improvement graft outcomes. There are now consensus guidelines for the use of the ‘virtual’ cross match in the UK.
With the advent of improved HLA antibody screening and identification, came the drive to improve organ allocation and utilisation. Kidneys from deceased donor organs are allocated via NHS Blood and Transplant in a nationally coordinated manner based on recipient and donor factors. There have been four kidney offering schemes in the UK with increasing refinements since the first Beneficial Matching scheme was established in 1989.
This scheme started in 2007, and by 2019 had enabled more than 1000 potential recipients with incompatible HLA or blood group live donors to receive live donor organs from other better matched live donors. This scheme has been a gamechanger by providing live donors for some who were otherwise untransplantable, and reducing the immunosuppressive burden which would have been necessary if transplant with the original live donor had been attempted.
Whilst the majority of work in UK H&I laboratories facilitates HLA compatible transplants, there are a small number of highly sensitized patients where the opportunity of an antibody compatible transplant is not realistic. In some cases these patients will still benefit if donor specific antibodies can be removed for a period to facilitate safe transplantation. Improvements in HLA antibody identification and monitoring have made it possible to develop such HLA antibody incompatible transplant programmes.
Authorship
David Briggs, Sue Fuggle, Joyce Popoola
Last Updated on June 5, 2026 by John Feehally