Donor-specific antibodies (DSA)

Donor-specific antibodies (DSAs) are recipient-generated immunoglobulins, primarily of the IgG class, that specifically target the Human Leukocyte Antigens (HLA) or non-HLA antigens present on a transplanted organ. These antibodies are formed following exposure to foreign antigens through previous transplants, blood transfusions, or pregnancy, a process known as sensitization. Once DSAs bind to the donor vascular endothelium, they initiate a cascade of damaging events including the activation of the classical complement pathway and the recruitment of inflammatory cells like natural killer cells and macrophages. This process leads to microvascular inflammation, tissue injury, and eventually antibody-mediated rejection (AMR). In clinical practice, DSAs serve as both a critical biomarker for monitoring graft health and a primary target for desensitization protocols. Therapeutic strategies focus on preventing their formation using maintenance immunosuppression or aggressively reducing their levels during rejection episodes. High-potency treatments include Imlifidase, which cleaves the IgG hinge region to rapidly neutralize DSAs, and proteasome inhibitors like Bortezomib that target the long-lived plasma cells producing them. Effective management of DSAs is essential for improving long-term allograft survival and expanding the pool of compatible donors for highly sensitized patients.

Other names

Anti-HLA antibodiesAlloantibodiesAnti-donor HLA antibodiesDonor-specific HLA antibodies

Drugs targeting donor-specific antibodies typically function by either physically removing the antibodies from circulation (plasmapheresis), enzymatically degrading the antibodies (IdeS/Imlifidase), depleting the B-cells or plasma cells responsible for their production (Rituximab, Bortezomib), or inhibiting the downstream inflammatory cascades such as the complement system (Eculizumab) or IL-6 signaling (Tocilizumab) triggered by antibody-antigen binding.