Abstract
Aim Presence of anti-donor HLA antibodues is a contraindication to transplantation in most solid organs. In contrast, most patients with high titer donor specific antibodies (DSA) and positive flow cytometric crossmatch (FCXM) still undergo liver transplantation. Antibody mediated rejection (AMR) may or may not develop after liver transplantation in such patients. We speculated that despite positive crossmatch results, cytotoxic function of existing and/or de novo DSA is what will ultimately predict development of AMR. Methods In this study we report two conflicting cases of liver transplant patients with high titer pre-transplant DSA and positive FCXM. Pre-transplant sera of patient A and B were retrospectively tested with a C1q assay to determine the cytotoxic function of DSAs. Results One patient (patient A) developed hyperacute AMR shortly after transplantation while the second patient (patient B) did not develop any signs of AMR and her post-transplant period was uneventful. In patient A, shortly after transplantation, serum amino transaminase and bilirubin levels became elevated. Serum HLA antibody testing showed high levels of class I and class II DSAs that resulted in positive T and B cell FCXM. Positive C4d staining of liver allograft biopsy indicated an episode of AMR. Patient was treated with plasmapheresis (days 1-9), Rituximab and IVIG (days 9-13) and Thymoglobulin (days 2-8). Levels of DSA and positive FCXM decreased overtime and 4 years post-transplant DSA antibodies were no longer present. In contrast, patient B did not develop any signs of post-transplant complications related to presence of HLA antibodies. Consistent with our hypothesis at the time of transplant, DSA of patient A were positive for C1q factor. In contrast C1q was negative on DSA of patient B. Conclusions We conclude that pre-transplant antibody testing and C1q assay should be considered as pre-transplant tests to be performed to liver transplant patients. Larger studies should be performed to confirm our findings.
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