Donor Specific Anti-HLA Antibodies Towards HLA Cw and HLA DP Should Be Considered as Pathogenic in Kidney Transplantation.

Abstract

It is widely accepted that HLA donor-specific antibodies (DSA) have a deleterious impact in kidney transplantation. However, non-classical preformed anti-HLA Cw and anti-HLA DP DSA are not considered in organ allocation policies and their clinical relevance is uncertain. Here we wondered whether anti-Cw/DP DSA should be considered as pathogenic through a retrospective study, comparing 48 patients transplanted with isolated preformed anti-Cw/DP DSA (Anti-Cw/DP DSA group) with (i) 104 matched HLA-sensitized kidney transplant recipients (KTR) with no DSA at D0 (No DSA group)and with (ii) 58 KTR with at least one identified preformed DSA other than anti HLA-Cw or HLA-DP antibodies (anti-A, -B, -DR, -DQ group or Classical DSA group). A positive flow cytometry XM in the anti Cw/DP DSA group was more frequent than in the No DSA group and as frequent as in the Classical DSA group. Two years after transplantation, graft survival and renal function were significantly lower in the anti-Cw/DP group than in the No DSA group, but not different from the Classical DSA group. Similarly, the biopsy-proven acute rejection-free survival was worse in the anti-Cw/DP and Classical DSA groups (with more inflammatory microcirculations lesions g+ptc) compared to No DSA group. Taken together, our results suggest that preformed anti-Cw and anti-DP DSA can exert the same deleterious effects that classical anti-A, -B, -DR, -DQ DSA. This might justify the systematic typing of HLA Cw and DP donor antigens and the detection of anti-Cw and anti-DP recipient antibodies as well as their inclusion in the kidney allocation algorithms.