Abstract
To determine whether the abrogation of development of donor specific antibodies (DSA) following ABO incompatible (ABOi) transplants is due to “accommodation” resulting in better graft outcome of ABOi renal transplants in comparison to ABO compatible (ABOc) renal transplants (RTx).
RTx recipients with ABOi (n=18) and ABOc (n=47) with similar demographics were selected for this study [Table 1]. Pre and post-transplant sera were analyzed for DSA to Class I and II human leukocyte antigen (HLA) using LabScreen Single Antigen assay. Both groups had no detectable HLA and were crossmatch compatible. ABOi patients underwent plasmaheresis, intravenous immunoglobulin and Rituximab to reduce antibodies to blood group antigens, while ABOc patients received intravenous thymoglobulin in the immediate post-transplant period. Both groups were maintained on identical immunosuppressive regimen with triple therapy.
Allo-immune response in ABOi and ABOc RTx patients was analyzed by measuring de novo development of DSA. None of the ABOi group developed DSA either to HLA Class I or Class II. In contrast, ABOc recipients developed DSA, 11 of 47 (23%). It is of significance that ABOi recipients with similar HLA mismatches to ABOc recipients failed to develop any detectable DSA which may account for lower incidence of acute rejection in ABOi group. In the ABOi only 2 of 18 (11%) developed acute rejection episodes which were reversible compared to 9 of 47 (20%) in the ABOc group. At the end of one year, glomerular filtration rate was also significantly better (p<0.04) in ABOi patients and further demonstrated superior long term function at the end of a five year period.
Our study demonstrates that desensitization using Rituximab, intravenous immunoglobulin and plasmapheresis for depleting antibodies in ABOi RTx patients prior to transplantation abrogates de novo development of DSA, likely due to accomodation, may account for the better outcome of the ABOi renal transplants.