Crossing low-level donor-specific antibodies in heart transplantation

Donor-specific antibodies (DSA) detected by solid-phase single-antigen bead (SAB) immunoassays have been associated with antibody-mediated rejection (AMR), cardiac allograft vasculopathy (CAV) and decreased survival after heart transplantation. The clinical relevance of low-level DSA is equivocal. This review examines the techniques used to define low-level DSA, the limitations of these techniques and recent clinical experience crossing low-level DSA.

Solid-phase multiplex bead immunoassays were introduced to solid-organ transplantation over 15 years ago. These technologies have a much greater sensitivity and specificity than older cell-based immunoassays. It was hoped that this increased resolution would lead to better outcomes by avoiding donors with antigens that transplant candidates produced antibodies against. Although some transplant patients with DSA show increased risk of AMR and decreased survival, a subset of patients with DSA at the time of transplant have outcomes comparable with patients with no DSA. Recent studies have demonstrated that DSA delineated according to titration studies and C1q assays better define low-level DSA that are well tolerated to cross. Early experience with crossing low-level DSA shows promise in kidney and heart transplantation.

Preliminary findings from heart and kidney transplant patients show acceptable outcomes after crossing low-level DSA. The policy of crossing low-level DSA increases the donor pool for sensitized heart transplant candidates.