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. From the 1980s these assays became central to supporting patient work up for transplantation and facilitating effective use of donated organs.
In the UK there is in 2026 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. Scientists in the UK have played a significant role in developing the assays used throughout H&I laboratories to support kidney transplantation.
Crossmatching
A crossmatch is required to assess histocompatibility between a prospective donor and recipient.
The complement dependent lymphocytotoxicity (CDC) crossmatch assay. Paul Terasaki (USA) and co-workers described the complement dependent lymphocytotoxicity (CDC) crossmatch assay which is still the platform for testing donor and recipient compatibility for most H &I laboratories around the world. The principle is to replicate in the laboratory what would happen if a transplant took place. Donor lymphocytes are incubated with recipient sera and if the recipient’s sera contained antibodies directed against donor HLA, there is cell lysis, a positive crossmatch. The introduction of this assay pre-transplant was fundamental in limiting the risk of hyperacute graft rejection due to donor specific HLA antibodies.
Flow cytometry crossmatch assay
In 1983 Bernie Carpenter (Boston, USA) and co-workers described a flow cytometric crossmatch assay, which has increased sensitivity over that of the CDC crossmatch, and is now used routinely in clinical kidney transplantation.
DNA based HLA typing
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.
HLA antibody identification
For many years the CDC assay was used for HLA antibody detection and identification. Patient sera was incubated with a panel of known HLA typed cells covering the majority of known HLA antigens allowing HLA antibodies to be determined. However, the advent of Luminex® based solid phase assays in the 1990’s revolutionised HLA antibody detection and identification, facilitating the screening and accurate identification of HLA class I & II antibodies in a patient sera.
With the advent of improved HLA antibody screening and identification, came the drive to improve organ allocation and utilisation. UK H&I scientists were in the forefront of initiatives to improve graft survival by reducing the need to undertake laboratory crossmatching pre-transplant. The so-called “Virtual” Crossmatch allowed selective omission of the pre-transplant crossmatch in deceased donor transplantation; patient and donor compatibility assessment were instead based on the donor HLA type and recipient HLA antibody history. Since 2021 there are UK consensus guidelines for virtual crossmatching which Cold Ischaemia Times and improve graft outcomes.
HLA incompatible transplantation
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 many cases these patients will still see a benefit if donor specific antibodies could be removed for a period to facilitate safe transplantation. Improvements in HLA antibody identification and monitoring have made it possible to develop HLA antibody incompatible transplant programmes.
Author: Joyce Popoola
Last Updated on June 2, 2026 by John Feehally