Background: There is increased interest in ABO-incompatible (ABOi) kidney transplantation (KTx) worldwide. With appropriate selection based on anti-ABO titer, reduction of natural antibodies (NAbs) by plasmapheresis and/or Rituximab and conventional immunosuppression; outcomes similar to ABO-compatible (ABOc) KTx can be achieved. It is generally accepted that pre-KTx reduction in NAbs (anti-ABO) results in a state of accommodation post KTx. The aim of this study was to determine whether NAbs induced accommodation also prevents alloimmunity to mismatched donor HLA and kidney self antigens (SAgs) and its impact on graft survival.
Methods: ABOi KTx (n=20) and a time matched cohort of ABOc KTx were enrolled and blood samples collected. Anti-ABO titers were measured pre, post KTx and donor HLA specific Abs (DSA) were measured by Luminex. Rejection confirmed by biopsy. Serum Abs against SAgs Collagen 4 (Col4) and fibronectin (Fibr) detected by ELISA. IFNΓ, IL17 secreting cells specific to SAgs enumerated by ELISPOT.
Results: There were no patient deaths with a median 2 year follow up. There was no difference in demographics including eGFR post KTx, delayed graft function etc. Number of HLA mismatches were similar and 3/20 ABOi KTx were 0 mismatches and both groups had no DSA prior to KTx. In ABOi KTx, 12/20 recipients were O group. Immunosuppression (MMF+Tacrolimus+Prednisone) was similar, except ABOi KTx received pre-transplant IVIG+Rituximab+Plasmapheresis. Anti-ABO titers returned to pre-KTx levels in 17/20 patients within 1 month KTx. Incidence of acute rejection in ABOi was 5% compared to 18% in ABOc (p=0.02). Incidence of denovo DSA in ABOi was 5% as opposed to 17% in ABOc KTx (p=0.02). One ABOi and 2 ABOc grafts failed due to AMR (p=0.5). In ABOi, 0% developed SAg specific T-cell or Abs against SAgs Col4 and Fibr, compared to 32% in ABOc (p=0.01).
Conclusion: ABOi KTx had significantly lower acute rejection, de novo DSA and complete lack of immune responses to SAgs Col4 and Fibr, even when anti-ABO titers returned. In contrast, ABOc transplants had higher incidence of DSA, acute rejection and immune response to SAg. Hence, we conclude that accommodation by NAbs following ABOi KTx also prevents immune responses against allo and tissue restricted SAgs and facilitate long term allograft survival.
To cite this abstract in AMA style:Subramanian V, Klein C, Phelan D, Wellen J, Chapman W, Shenoy S, Mohanakumar T. ABO-Incompatible Kidney Transplantation Protects the Graft from Natural Antibodies Induced Damage and Prevents Immune Responses to Donor HLA and Kidney Associated Self Antigens Leading to Long Term Rejection Free Survival [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/abo-incompatible-kidney-transplantation-protects-the-graft-from-natural-antibodies-induced-damage-and-prevents-immune-responses-to-donor-hla-and-kidney-associated-self-antigens-leading-to-long-term-re/. Accessed May 7, 2021.
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