Introduction: Highly-HLA sensitized patients are at risk for developing donor specific antibodies (DSA) & ABMR post-transplant (tx). However, incidence and risk of acute rejections (AR) in HS patients who developed dnDSA after tx is unclear. Here we examine the risk for ABMR in HS (>80% PRA) patients after DES who were DSA+ v. DSA- at time of tx. In addition, we examined the incidence and impact of dnDSA development and compared with those who remained dnDSA-. Patients & Methods: From January 2013 to June 2015, 79 HS patients (PRA>80%) received kidney transplantation after desensitization with IVIG (2gm/kg, maximum 140gm x2 doses) + rituximab (x1) ± PLEX. All received induction with alemtuzumab x1 and maintained with tac/mmf/pred taper. DSA-RIS (relative intensity score) was used to represent MFI intensity of DSAs (2=MFI<5000; 5=MFI 5000-10,0000 and 10=MFI>10,000) and were calculated @transplant, 1,3,6,12 & 24M post-transplant. We also tracked dnDSAs. Results: Patients were divided into 2 groups: G1: DSA+ (n= 44) vs. DSA- (n= 35) @tx and G2: dnDSA+ (n=16) v. dnDSA- (n=63) post-tx. In G1, ABMR occurred in 27% in DSA+ v. 20% in DSA- (p=NS); freedom from graft loss was not different, 93% v. 91% (p=NS), neither was freedom from acute rejection by DSA status (68.2% in DSA+ v. 68.6% in DSA-, p = NS). By 1 year, rejection rates were similar, although a delay in rejection was seen in DSA- patients for the 1^st 6M. DSA RIS in DSA+ @ transplant, 1,3,6,12 & 24M were 8.0±4.5, 1.9±2.9, 1.6±2.7, 1.3±2.3, 0.8±1.6 & 0.4±1.2, respectively. In G2: 16 patients (20%) developed dnDSA, range from 3 days to 270 days, {25% class I, 44% class II, 31% class I and II, (approximately 10%/year)} v. 63 (80%) without dnDSA (dnDSA-). ABMR occurred in 56% in dnDSA+ v. 16% in dnDSA-. There was a significant impact of dnDSA development on AR {HR = 2.73 ; CI = 1.06-7.02; p= 0.03}. Conclusions: After DES, DSA+ or DSA- at time of transplant has no impact on incidence of AR or graft loss @24M. As a group, DSA-RIS fell predictably after desensitization post-transplant and maintained at low level for up to 24M. dnDSA development was comparable to that reportedly for non-HS patients (~10%/year) and was associated with a significant risk for AR. Frequent monitoring of HS patients for dnDSA is essential and may prompt early treatment.

CITATION INFORMATION: Vo A, Choi J, Kahwaji J, Mirocha J, Peng A, Villicana R, Jordan S. Incidence & Impact of De Novo DSA (dnDSA) Formation on Transplant Outcomes in HLA-Sensitized (HS) Patients Transplanted After IVG+Rituximab Desensitization (DES). Am J Transplant. 2016;16 (suppl 3).

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