#2806 Role of non-HLA antibodies in pre-transplant evaluation of antibody-mediated damage risk

Abstract Background and Aims Donor-specific HLA antibodies (HLA-DSA) contribute to antibody-mediated rejection (ABMR) after kidney transplantation (KT) and worse graft-survival. Non-HLA antibodies may play a role in the development of ABMR in the presence of HLA-DSA or in the development of microvascular inflammation (MVI) in the absence of HLA-DSA. Considering both antibodies in potential recipients before or after KT could enhance the prediction of post-KT ABMR/MVI. Method Retrospective study of a cohort of 169 KT recipients with: a) pre- and post-KT sera; b) follow-up HLA antibody monitoring; and c) follow-up biopsies. We determined the presence of 60 non-HLA antibodies in sera with a multiplex test: the Single Non-HLA Beads kit (LIFECODES®) on a Luminex® platform. We obtained an absolute number of positive antibodies and a sample MFI ratio sum according to which we stratified results into quartiles. Results Pre-KT, we detected a 15.4% of KT recipients with high HLA sensitization (cPRA >50%), being 8.3% HLA-DSA, and non-HLA antibodies in 85% of KT recipients, with a median of 3 (2-5) antibodies and a median MFI ratio sum of 10.1 (2.9-18.5). During a median follow-up of 60 (18.5-89) months 73 patients developed ABMR/MVI. We observed that a high burden of pre-KT non-HLA antibodies was associated with a higher risk of ABMR/MVI, regardless of HLA sensitization and pre-KT HLA-DSA. Notably, 57% of patients with ABMR/MVI had a high non-HLA burden before KT and 24.6% had a HLA cPRA >50%. Altogether, 68.5% of these patients showed either a high HLA sensitization or a high non-HLA burden before KT (Figure). Conclusion A high non-HLA preTR non-HLA antibody burden detected with a multiplex panel allows identification of patients more likely to develop ABMR/MVI, irrespective of the presence of anti-HLA antibodies.