**3. Clinical relevance of antibody mediated rejection**

AMR is estimated to occur in 3–10% of transplant recipients and it represents 20–30% of episodes of acute rejection [7]. Although less common than cell mediated rejection, AMR is generally recognized to have a worse prognosis and requires different forms of therapy [9]. In the 1960s anti-HLA antibodies were recognized as a cause for allograft rejection following reports of hyperacute antibody mediated rejection in patients with antibodies reactive to donor lymphocytes [10, 11]. Patel and Terasaki's landmark study documented immediate graft failure in 24 of 30 (80%) of the patients with circulating donor reactive antibodies identified by a positive cytotoxicity crossmatch [12]. This led to the universal practice of antibody screening by complement dependent cytotoxicity (CDC) crossmatch prior to renal transplantation and the avoidance of transplantation in patients with a positive crossmatch. Therefore, until the mid-1980s, acute cellular rejection, as opposed to antibody mediated rejection (AMR), was considered the major barrier to successful [13]. The advent of calcineurin inhibitors (CNIs) in the 1980s led to a significant decline in incidence of acute rejection and a consequent improvement in short term graft survival rates [14]. Today, cellular rejection seldom causes graft loss [15]. However, contemporary data suggests that these gains have not led to sustained improvement in long-term graft survival [16]. Reasons for the lack of improvement in long-term graft survival have been a topic of much debate and most late graft losses were attributed to either chronic allograft nephropathy (CAN) or death with a functioning graft [17]. Although, the multifactorial nature of late renal allograft loss makes therapeutic intervention challenging [18] prevention and treatment of AMR holds the key to optimizing long term graft survival.

Exposure to non-self HLA by way of pregnancy, blood transfusion or transplantation may lead to the development of circulating anti-HLA antibodies. ESRD patients who are sensitized to HLA by prior exposure have a prolonged wait-time for transplantation and reduced transplant rates. Removal of pre-formed circulating donor specific antibodies (DSA) by various desensitization techniques allows transplantation of many of these biologically disadvantaged patients [19–21] However, such HLA incompatible kidney transplants recipients are at increased risk for developing AMR.A high percentage of episodes of AMR are difficult to treat and may cause immediate graft loss or delayed transplant glomerulopathy [22]. Therefore, AMR remains a significant impediment to the success of transplantation in this subset of patients.
