2239 Identification of non-HLA antibodies associated with the development of antibody-mediated damage after kidney transplantation

Abstract Background and Aims Non-HLA antibodies may play a role in the development of antibody-mediated rejection (ABMR) in the presence of donor-specific anti-HLA antibodies (HLA-DSA) or microvascular inflammation (MVI) without HLA-DSA in kidney transplantation (KT). The development of multiplex panels allowed the analysis of multiple antibodies simultaneously and new antibodies potentially related to ABMR/MVI have been identified. 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 using a multiplex test: the Single Non-HLA Beads kit (LIFECODES®) suitable for the SAB assay performed using Luminex® technology. Results Pre-KT, we detected non-HLA antibodies in 85% of the recipients, with a median of 3 (2-5) positive antibodies. During follow-up, 73 patients developed ABMR/MVI. Pre-KT, in a univariate analysis including the presence of HLA-DSA (8.3% in the cohort) we detected 7 antibodies individually associated with ABMR/MVI. In multivariate analysis (Figure) GSTT1, NCL, PLA2R1 and Thyroglobulin antibodies together with HLA DSA were significantly associated with the development of ABMR/MVI, although only GSST1 and Thyroglobulin appear in a relevant number of patients (>10 patients) involved in 32 cases of ABMR and 6 cases of MVI. Post-KT, only the detection of anti-GSTT1 antibodies in sera 1- and 3-years post-TR was associated with ABMR/MVI in 3-year biopsies. Conclusion Pre-KT the detection of antibodies against GSST1 and Thyroglobulin using a multiplex non-HLA antibody detection panel is independently associated with the development of ABMR/MVI during follow-up. Post-KT detection of GSST1 is also associated with ABMR/MVI in 3-year biopsies. No of patients HR 95% CI p-value APOL2 12/169 1.585 0.693-3.626 0.275 GAPDH 8/169 1.035 0.386-2.777 0.946 GSTT1 30/169 2.178 1.243-3.815 0.007 LPHN1 4/169 2.880 0.942-8.808 0.064 NCL 6/169 3.322 1.204-9.164 0.02 PLA2R1 6/169 3.089 1.098-8.686 0.033 Thyroglobulin 41/169 1.930 1.155-3.225 0.012 HLA-DSA pre-KT 14/169 2.706 1.343-5.450 0.005