P052 Antibody mediated rejection in a cardiac transplant case; to C or not to C

Background Due to the less sensitive nature of the historical assays and lack of data, and the low expression level of the HLA-C antigens, the role of pre-transplant HLA-C antigens in solid organ transplantation is less clear. Herein we describe a cardiac transplant case were patient was transplanted in the presence of donor specific antibody (DSA) to HLA-C antigen and a negative flow cytometric crossmatch; however, shortly post-transplant they developed antibody mediated rejection (AMR) due to C1q-fixing DSA to the HLA-C antigen. Method IgG and C1q-fixing HLA antibodies were detected using the Single Antigen luminex solid phase assay (One Lambda, Thermo Fisher). While the sole sensitizing antigen could not be determined, HLAMatchmaker was utilized to identify antibody specificities to a shared epitope, 76VRN. Flow cytometric crossmatches (FCXM) were performed on negatively selected (StemCell Technologies™ pronase-treated lymphocytes. T cell FlowDSA crossmatch (One Lambda, Thermo Fisher) was performed at the Southwest Immunodiagnostics, Inc., Laboratory. Results Regardless of the presence of relatively strong DSA to HLA-C antigens, MFI ranging from 6,000–14,000, T and B cell FCXM were negative. To further understand the clinical relevance of antibodies to the HLA-C antigens, sera was sent out for FlowDSA crossmatch testing. Two surrogate donors, one with DSA to C7 and one with DSA to C7 and C8, were both T cell positive by FlowDSA crossmatch. Nevertheless, due to clinical urgency patient was transplanted in the presence of pre-transplant DSA to HLA-C7 (MFI 12,600) and a negative FCXM. Approximately 10 days post-transplant patient developed clinical and biopsy proven AMR. Single antigen solid phase assay showed elevated DSA to C7 (MFI 19,500) and C17 (MFI 6,500). In agreement with the biopsy results, the post-transplant C1q Single Antigen assay was positive for C7 as well as the antigens carrying the shared epitope 76VRN. Conclusion Pre-formed HLA-C antibodies to shared epitopes can cause acute AMR. The FlowDSA crossmatch enhanced detection of such deleterious antibodies more efficiently than the conventional flow crossmatch assay. Six months post-transplant the patient is stable; however, the long term clinical relevance of such antibodies on the graft outcome remains to be determined.