Donor-Specific Biomarker Predicts Liver Transplant Rejection Independent of Recipient

By Megan Brooks

August 24, 2021

NEW YORK (Reuters Health) - Researchers from France have identified a donor-specific biomarker that can predict rejection of a liver transplant, independent of the recipient.

The prognostic marker - class I HLA evolutionary divergence (HED) of the donor - can be determined quickly at no additional cost as soon as the HLA genotype of the donor is known and has the potential "before transplantation when possible, to choose the best liver graft (for recipients with high risk of rejection) and after transplantation to modulate the immunosuppressive drugs," Professor Cyrille Feray of the Hepatobiliary Center at Hopital Paul-Brousse AP-HP, in Villejuif, told Reuters Health by email.

Allograft rejection depends on HLA proteins expressed by donor and recipient cells, which vary between individuals. Greater compatibility in HLA proteins between donor and recipient lessens the likelihood of organ rejection.

"The HED, a continuous metric quantifying the peptidic differences between two homologous HLA alleles, reflects the breadth of the immunopeptidome presented to T lymphocytes," the researchers explain in Annals of Internal Medicine.

The HED has emerged as a strong determinant of survival in patients with cancer treated with immune-checkpoint inhibitors and in leukemia patients undergoing allogeneic hematopoietic-stem-cell transplant.

The researchers assessed the potential effect of donor or recipient HED on liver transplant rejection in 1,154 adults and 113 children who had a liver transplant between 2004 and 2018.

The class I HED of the donor was significantly associated with acute and chronic rejection in adults and acute rejection in children.

The higher the HED of the donor, the more frequent rejection, the researchers found, and this relationship was independent of the HLA compatibility of the donor and recipient.

There was no effect of either donor class II HED or recipient class I or class II HED on the incidence of liver lesions in adults or children.

"The availability of donor HED could allow for better allocation of liver grafts when possible; for example, by avoiding donors with high HED values for recipients at high risk for rejection," the researchers say.

"Alternatively, HED could be considered in personalized strategies to optimize immunosuppression as a function of the risk for rejection. Finally, the role of HED in other transplant types where HLA matching (and occurrence of donor-specific anti-HLA antibodies) is crucial, such as kidney or lung transplant, should be investigated," they add.

This research had no commercial funding, and the authors report no conflicts of interest.

SOURCE: Annals of Internal Medicine, online August 23, 2021.