What are donor-specific antibodies and why do we test for them?

A quick refresher on HLA antibodies: Class I molecules are found on almost all nucleated cells. Class II molecules are found on antigen-presenting cells, B cells, and activated T cells. HLA matching is most important in bone marrow transplant and kidney transplant. In liver transplant, HLA matching may be beneficial but not so much that it is routinely performed; ditto for heart and lung transplant.

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Choo, 2007

Donor-specific antibodies (DSA) are HLA antibodies that are thought to contribute to rejection of the graft (allograft loss). They can be either class I or class II, although class II are more common.

DSA can be found pre-transplant (present in the recipient before transplantation occurs) or de novo (antibodies form in the recipient at any time after the transplant). Pre-transplant DSA are identified through panel reactive antibody (PRA). PRA is important because according to the OPTN, “Nearly a third of the OPTN renal transplant wait list is sensitized patients with a PRA of 10% or more. These candidates wait significantly longer than non-sensitized patients do and once transplanted suffer a greater risk of graft loss from rejection,” so these patients get additional “points” on the transplant list.

DSA can form at any time, although they are most commonly found <1 year after transplant. One study of kidney transplants found that after 4 years, 20% of patients with undetectable pre-transplant DSA will be found to have DSA, and that within 3 years, 25% of those patients will have graft failure. However, it must be noted that the mere presence of DSA does not equal rejection. Rejection is a diagnosis that must be made through pathology.

DSA in and of themselves do not need to be “treated,” although they are a risk factor for rejection. When and how to treat DSA is way above my paygrade, but suffice to say that if “DSA” are invoked, start thinking about the treatment of antibody-mediated rejection. There are a variety of strategies including ATG, upping doses of MMF or tacro, IVIG, and new monoclonal antibodies like bortezomib and eculizumab.