DQ Molecules Are The Principal Stimulators of De Novo Donor Specific Antibodies in Non Sensitized Pediatric Kidney Recipients.

Donor specific humoral alloimmunity has been recently recognized as the principal cause of chronic antibody mediated rejection (CAMR), a major obstacle to long term graft survival. Data on the different HLA-antibody (Ab) categories in pediatric kidney recipients developing de novo donor-specific Abs (DSA) after transplantation are scarce. We retrospectively evaluated 82 consecutive non-sensitized pediatric recipients of a first kidney graft for de novo HLA Ab occurrence and antigen specificity. HLA class I and II IgG antibodies were evaluated by means of bead-based assays with a Luminex platform. At a median follow-up of 6-years, 29% of patients developed de novo DSA while 45% had de novo non-DSA.DSA appeared at 25-month median time post-transplant and were mostly directed towards HLA-DQ antigens. Considering each HLA antigen, the estimated rate of DQ DSA (7.55 per 100 person-years) was much higher than the rates observed for DSA directed to A, B and DR loci (2.56, 1.83, and 0.26 per 100 person-years, respectively). The HLA-DQ Ab recognized determinants of the DQβ chain in 70% of cases, α chain in 25% of cases and both chains in one patient. Non-DSA appeared earlier than DSA, were largely directed against HLA-class I specificities that belonged to HLA -A and -B related cross-reacting epitope groups (CREG) in 56% of cases. Our results indicate a need for evaluating HLA-DQ antigen compatibilities in kidney allocation in order to minimize post-transplant development of de novo DSA, known to be responsible for CAMR and graft loss.