OR38 Antibody mediated rejection in heart transplantation: Looking beyond HLA to non HLA targets

Abstract

Aim Non-HLA antibody monitoring using endothelial crossmatch (XM-ONE®) and Angiotensin Type I Receptor (AT1R) antibody tests was performed to determine efficacy of therapeutic plasma exchange in the treatment of antibody mediated rejection (AMR) in two heart transplant recipients. Methods AMR was diagnosed on biopsy using ISHLT criteria including C4d and C3d staining via immunofluorescence. Multiple Luminex® immunoassays were used to confirm the absence of donor specific HLA antibody (DSA). XM-ONE® kits were used to isolate endothelial cell precursors from surrogate donor whole blood and to detect IgG endothelial cell reactive antibodies (Absorber AB). The threshold for a positive crossmatch was a ratio >1.3 over negative control serum (50 Median Channel Shift). AT1R specific antibodies (AT1R-Ab) were detected using an ELISA (CellTrend) and the threshold for positivity was >17 U/ml. Results Analysis of AT1R-Ab levels and endothelial crossmatch results were correlated to ISHLT biopsy results and allograft function following AMR treatment with alternate day plasmapheresis and low dose IVIg. AT1R-Ab levels remained strongly positive throughout treatment for both patients. XM-ONE® crossmatch reactivity decreased and correlated with improved function and a reduction in C4d and C3d immunofluorescence in both patients. Conclusion These results suggest heart recipients with biopsy proven AMR in the absence of donor specific HLA antibody may be the result of non-HLA specific antibodies. Multiple non-HLA antibody assays may be needed to monitored efficacy of AMR treatment.