Kidney Research Northwest

Investigating HLA-specific Antibodies following Renal Transplant

Petra Goldsmith is a Transplant Surgeon in the Mersey Deanery and part-time PhD student at the University of Liverpool. Her research, with Professor Andrew Jones’ group in the Institute of Integrative Biology and the Tissue Typing Laboratory at the Royal Liverpool Hospital investigates antibodies which can form following kidney transplant and cause short and long-term damage to the transplant; in the worst cases, if the antibodies are aggressive they can result in transplant failure.

The ways of detecting antibodies both pre- and post-transplant have been the subject of many successful scientific developments of late. Paul Terasaki first developed the so called “CDC cross-match” in which recipient cells were mixed with donor serum – if antibodies were present in the donor serum they would attack the recipient cells and cause them to be killed, a process called lysis, which can be seen down a microscope. For the last decade or so, new techniques have been developed which can identify if any antibodies are present and the specific types, which means that it is possible to know in advance if a donor and recipient are compatible – this can save precious hours once deceased organs are available by avoiding the need for a lengthy cross-match to be performed before the transplant goes ahead.

Petra’s work involved testing serum from a population of kidney transplant patients from the Royal Liverpool Hospital for these antibodies. She performed the standard test (called Single Antigen Bead testing) and also some special modifications which help to remove the inhibitory effect of other components of the immune system which can falsely appear as negative results on the standard assay. She published this work in 2020 in Transplant Immunology journal showing the first large study of how these antibodies are present in an uncensored post-transplant population and identified that about 20% of routine post-transplant patients will have at least one antibody demonstrating this inhibitory property. She also compared the effectiveness of three special tests at removing the inhibitory immune effects, and was the first to describe the effect of one of these tests in a large study (Transpl Immunol. 2020 Jun 20 62C;101310. doi: 10.1016/j.trim.2020.101310).

She continues her work which is now focusing on looking at the presence and reactivity of sub-classes of antibody which are special subsets that appear at different times in the immune response and have different effects on the kidney. Although many are very damaging, it is believed that some have a protective effect and once she has identified the subclass profile for each patient she will be able to relate these findings to kidney transplant function and outcome.

Research Partners
Liverpool University The Royal Liverpool and Broadgreen University Hospital
Supported by
Mitchell Charlesworth