Introduction:Donor specific anti-HLA antibodies (DSA) are a major cause of antibody-mediated rejection (ABMR) and poor graft outcome in kidney transplant recipients (KTR). Critical issue is whether detected antibodies would be clinically relevant. Given complement activation is a contributor to AMBR, evaluating the ability of DSAs to activate the complement cascade is important.Our study was to evaluate to whether C3d-binding DSA can predict ABMR and graft failure in stable KTRs. We compare prevalence of ABMR and graft outcome between SA-DSA with C3d-DSA test, and also analyze the risk factors for graft failure.

Method: We examined 220 stable KTRs for DSAs from July of 2013 to July of 2016. We biopsied 24 recipients who were on positive on Luminex PRA and tested C3d-binding DSAs and SA-DSA assays.

Result:10.9% (24of 220) of stable KTRs had DSAs on Luminex PRA, Median timing of DSA occurring was 9.6(0.2-24) year of posttransplantation.Mean follow up was 18.5(1-50) month. 18 of 24 (75%) had DSAs on SA Luminex assays. 11 of 24 (46%) had C3d-binding DSAs. Most of DSAs belong to class2, anti-DQ antibodies (88.9%, eight of 9). Three patients had graft failure at 2.6 (0.5- 3) year after ABMR. Incidence of ABMR and microvascular inflammation was significantly higher in C3d-DSA (+) than C3d-DSA (-) (7 of 11, 63.3% vs. 1 of 13, 7.7%, P<0.01). ROC curve showed C3d-class2 is more accurate test to detect ABMR than class2-DSA (P<0.001). Significant predictors of graft failure on multivariate analysis were high serum creatinine at the time of biopsy, ABMR, CABMR and Class2, C3d-DSA (+).Class2,C3d-DSA (+) had significantly lower death censored graft survival (DCGS) than Class2, C3d-DSA(-), Class2 SA-DSA (+) tended to have lower DCGS but did not reach significance.

Conclusion:We demonstrated that C3d-binding anti-DQ DSA was significantly associated with a high risk for ABMR and graft failure in stable KTRs. However, our study was too small and short, so we need to verify with larger and longer-term study. We suggest immune surveillance with C3d-DSA and subsequent allograft biopsy may be useful method to recognize ABMR early and to prevent graft failure in stable KTRs.

CITATION INFORMATION: Lee D, Kim B, Kim J, Kim I, Chun M. C3d-Binding Anti-DQ DSA Is Associated with a High Risk for Late ABMR and Graft Failure in Stable Kidney Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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