A circulating antibody panel for pretransplant prediction of FSGS recurrence after kidney transplantation

摘要: Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause accelerated graft loss. To evaluate pathogenic antibodies (Abs) in rFSGS, we processed 141 serum samples from 64 patients with and without primary rFSGS 34 non-FSGS control transplanted at four hospitals. We screened about 9000 antigens pretransplant sera selected 10 Abs targeting glomerular for enzyme-linked immunosorbent assay (ELISA) validation. A panel seven (CD40, PTPRO, CGB5, FAS, P2RY11, SNRPB2, APOL2) could predict posttransplant FSGS recurrence 92% accuracy. Pretransplant elevation anti-CD40 Ab alone had the best correlation (78% accuracy) risk transplantation. Epitope mapping CD40 customized peptide arrays demonstrated altered immunogenicity extracellular domain rFSGS. Immunohistochemistry differential expression compared to controls. Anti-CD40 purified were particularly human podocyte cultures. Injection anti-CD40/rFSGS enhanced suPAR (soluble urokinase receptor)–mediated proteinuria wild-type mice, yet no sensitizing effect was noted mice deficient or that received blocking CD40. In conclusion, can help identify high before Intrarenal (and possibly other specific antigens) an important contributor disease pathogenesis. Human trials therapies are warranted their efficacy preventing improving survival.