P053 DP donor specific antibodies pre-renal transplant: Mean fluorescence intensity and epitope pattern alone is not predictive of crossmatch result or clinical outcome

Abstract

The clinical significance of HLA-DP donor specific antibodies (DSA) detected with solid phase assays in recipients of renal transplants remains poorly defined. Recent literature has elucidated that many patients have a HLA-DP antibody pattern of reactivity against broad cross-reactive epitopes which may be more clinically significant. Typically, a DSA that reacts at a mean fluorescence intensity (MFI) of greater than 5000 results in positive crossmatch. We present two cases with pre-transplant HLA-DP DSAs at high MFI (>5000) directed against cross-reactive epitopes identified on virtual crossmatch which resulted in negative and positive flow crossmatch respectively. Case 1 is 57 yr old male who received a deceased donor renal transplant in 2015. He was known to have a HLA-DP9 DSA DED epitope reactivity pattern at 7,333 MFI detected by Luminex bead assay against his donor on peak serum. Pre-transplant crossmatch was negative and he proceeded to transplant. Current creatinine is stable at 150 μmol/L and there are no episodes of rejection. Case 2 is 67 yr old female who remains on the deceased donor list awaiting renal transplant with a cPRA of 99%. She has had 3 offers where she has had a HLA-DP1 or HLA-DP3 DSA DEAV epitope reactivity pattern at 10,000 MFI against her donors resulting in flow B-cell positive crossmatch. Crossmatch with donor cells known not to express DP DEAV epitope antigens have been negative. The current cases illustrate that HLA-DP DSAs at high MFI with epitope reactivity may not necessarily result in a positive flow crossmatch. The differential crossmatch results for these two recipients may be related to variable HLA-DPB1 antigen expression in the donor rather than MFI and/or epitope pattern reaction in the recipient. Avoidance of transplant in the context of high MFI HLA-DP DSA epitope cross-reactivity pattern may not be necessary and can be associated with acceptable clinical outcome in the context of a negative pre-transplant crossmatch. HLA-DPA DSAs that have an epitope pattern of reactivity resulting in positive crossmatch are still avoided. Adding DP DSAs to the allocation algorithm without the opportunity to perform flow crossmatch does not allow for accurate immunological risk assessment and may prevent the opportunity for successful transplant. C. Ribic: 1. Grant/Research Support; Company/Organization; Leo Pharma; Astellas. 3. Speaker’s Bureau; Company/Organization; Leo Pharma; Astellas.