New opportunities for the HLA-sensitised transplant patient   

The Irish Nephrology Society Annual Scientific Meeting 2026  heard an informative update on the management of highly-sensitised transplant patients from Prof Rhys Evans, Associate Professor of Renal Medicine and Consultant Transplant Nephrologist, Royal Free NHS Trust, London, UK.

Transplantation is often extremely difficult and significantly delayed for patients who have developed antibodies against foreign human leukocyte antigens (HLAs), the conference was told.

Beginning with historical context, Prof Evans described the first successful kidney transplant, performed by Dr Joseph Murray in Boston in 1954 between genetically identical twins. Since then, one of the “greatest challenges” in transplantation has been overcoming the genetic barriers between donor and recipient, he said.

“We are now transplanting people more than once,” he said. Prof Evans acknowledged why the challenge of sensitisation is becoming increasingly relevant, as more patients undergo multiple transplants in a single lifetime and subsequently develop antibodies. Once sensitisation occurs, it is “very difficult to overcome”.

Until recently, modern approaches to desensitisation remained largely unchanged from early strategies like plasma exchange, steroids, and cyclophosphamide. “This remains a real unmet need, but we are now making some progress.”

Around 15 per cent of patients on waiting lists have a calculated panel reactive antibody score above 85 per cent, Prof Evans told delegates, and while average transplant waiting times are three to four years, many of these sensitised patients wait considerably longer. Prof Evans emphasised the importance of exploring living donation, particularly if a HLA-compatible donor is available, given the superior outcomes compared with deceased donor transplantation.

He then presented a case report to illustrate “an extreme example” of the highly-sensitised patient.

The woman received her first transplant as a child, which subsequently failed. Highly sensitised, she then spent a number of years on dialysis while awaiting a second transplant. Prof Evans described using her list of unacceptable HLA antigens to calculate her likelihood of receiving a compatible kidney and finding she effectively had no potential donors.

Emphasising the importance of assessing the clinical significance of donor-specific antibodies (DSAs) and antigen delisting, he noted that “not all antigens are the same”.

Antigen delisting refers to removing previously identified unacceptable donor HLA antigens from a transplant candidate’s sensitisation profile after further testing shows the antibodies are either no longer present or clinically insignificant, which can successfully expand the compatible donor pool for these patients.

The conference heard that the Royal Free Hospital has developed a local staged approach to antigen delisting, although no national UK protocol currently exists. Following careful review of class I and class II antibodies, the featured patient’s list was modified, and she subsequently received four potential donor offers. However, Prof Evans remarked that one delisted antigen was later relisted after positive crossmatches. “Relisting is a constant process,” he explained.

Prof Evans then discussed imlifidase – a recombinant enzyme derived from Streptococcus pyogenes that rapidly cleaves immunoglobulin-G antibodies.

“The beauty of the drug is that its action is immediate,” he said. By eliminating circulating DSAs within approximately 48 hours, imlifidase can create a window that allows transplantation to proceed despite pre-existing sensitisation. However, patients are vulnerable to DSA rebound and antibody-mediated rejection (AMR) in the first few weeks after transplantation, he said. While the overall AMR rate is approximately 40 per cent, Prof Evans noted that some episodes may be subclinical and detectable only through surveillance monitoring. Five-year imlifidase follow-up data, albeit limited, have shown encouraging outcomes with no significant long-term safety concerns.

Prof Evans concluded that antigen delisting and imlifidase are providing new opportunities for highly-sensitised patients who previously had little realistic prospect of receiving a kidney transplant.