The development of de novo donor specific antibodies (dnDSA) usually leads to a reduction in renal graft survival. The deleterious influence of dnDSA is most significant when they accompany acute cellular (ACR) or antibody mediated rejection (AMR) or shortly thereafter. However, the significance of dnDSAs found in the absence of a demonstrable clinical effect remains unclear. Thus, the value of screening for dnDSA is uncertain. In this study, 185 adult renal allograft recipients consecutively transplanted in our center from Jan. 2012 to Sept. 2014 were monitored for the appearance of dnDSA. Serum samples were obtained at 1 (n=129), 3 (n=135), 6 (n=101), 9 (n=65), 12 (n=77), 16 (n=47) and 24 (n=26) months. Patients received rabbit anti-thymocyte globulin (83%) or basiliximab (17%) induction and were given tacrolimus, mycophenolic acid and prednisone maintenance therapy. A total of 16 (8.6%) patients developed dnDSA. The average HLA MM among patients with dnDSA was slightly greater compared to patients without dnDSA (3.6 vs. 2.9, p=0.06). However, the degree of alloantibody sensitization prior to transplant was equivalent. Five of the 16 (31%) dnDSA were found in association with acute rejection (3 ACR and 2 AMR+ACR). Anti-DQ dnDSA were found in all of these 5 patients. Late rejections at 9 and 16 mos. were due to medication non-adherence and, despite aggressive therapy, resulted in graft loss. Early rejections at 0.5, 1 and 2 mos. were successfully reversed. In the remaining 11 cases, dnDSA were found on routine surveillance at 1-3 mos. (n=6), 6-9 mos. (n=4) and 12 mos. (n=1). Anti-DQ dnDSA were noted in 4 (36%), anti-DR in 5 (45%) anti-Class I in 4 (36%). High dnDSA MFI titers (≥ 9,500) were more commonly associated with rejection compared to those noted through screening (100% vs.18% p<0.01). In 4 screened patients, dnDSA persisted whereas in 7 they lasted 1-8 months. Nine of the 11 patients with dnDSA found by screening underwent renal biopsy. All 9 biopsies had no evidence of ACR or AMR and were not treated. Over a follow up period of 4-16 mos., no late rejections occurred in this group and renal function remained well preserved with average creatinine of 1.2±0.3 mg/dl. In summary, dnDSA found by surveillance are: of lower titer, often transient in duration and do not predate rejection or graft dysfunction. We conclude that the value of screening for dnDSA is not supported by these preliminary data.

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