Post Transplant DSA - Professor Richard Kirk 2023

Transplant Challenges
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Post Transplant DSA

HLA Antibodies (Post Transplant)

The use of induction and maintenance immunosuppression is designed to reduce the recipient immune system from activating T cells and, in turn, B cells. Despite this HLA antibodies may develop and if they are targeted at donor HLA glycoproteins they are called donor specific antibodies and referred to as newly detected DSA (ndDSA) or denovo DSA. They may be transient or persistent.

Transient DSA

Transient DSAs are frequently seen early after transplant and this may be because of the ischemic-reperfusion injury around the time of donor retrieval and implantation which activates the innate immune system, causing inflammation. However any inflammatory trigger (e.g. cell mediated rejection, viral infection) may promote donor HLA expression and, depending on the effectiveness of immunosuppression, lead to T & B cell activation. Activated B cells transform into short lived plasma cells which produce donor specific antibodies. Short lived plasma cells have a life of a few days, and so as the inflammation subsides, so does HLA expression, short lived plasma cells are no longer produced and the DSA levels decline.

Persistent DSA

The short lived plasma cells may go onto become long lived plasma cells (LLPC). LLPC have the capacity to continually produce antibody, even in the absence of ongoing rejection or inflammation. They may however not cause rejection if HLA is not expressed. However if, for example immunosuppression is inadequate and rejection occurs or the myocardium is inflamed by a virus, then HLA will become expressed and antibody mediated rejection can occur. Persistent DSA are associated (amongst other factors e.g. metabolic syndrome) with worse graft survival and coronary allograft vasculopathy (CAV). An explanation may be that expression of HLA may not be an all or nothing phenomenon but may be at a low level, or intermittent, allowing DSA to cause progressive endothelial damage.

In summary DSA may be transient or persistent and baseline levels can rapidly increase in response to HLA expression for example during rejection and exacerbate the situation. Removing the antibodies through using some or all of the methods described in the desensitization section may therefore prevent further escalation of rejection or reduce the likelihood of graft loss and CAV. Knowing what to do with stable patients and normal graft function, who have persistent DSA even at high levels is problematic as desensitization clearly reduces the effectiveness of the whole immune system and is not without consequences.