Immunological barriers in ABO-incompatible kidney transplantation: How to overcome

Background: Various desensitization strategies are used to overcome immunologic barriers such as anti-human leukocyte antigen-donor-specific antibody (HLA-DSA) and anti-ABO blood group incompatibility. Materials and Methods: Three index cases of ABO-incompatible (ABO-i) kidney transplantation from living-related donors are discussed. Each recipient was evaluated by complement-dependent cytotoxicity crossmatch, flow cytometric crossmatch, lysate-based crossmatch, and single-antigen bead Luminex assay and anti-A, B isoagglutinin titer. The desensitization protocol included 500 mg of rituximab, followed by 2-10 sessions of plasmapheresis with basiliximab/antithymocyte globulin induction. Results: Case 1: A patient received the third transplant as ABO-i transplant, with no anti-HLA-DSA. Anti-ABO antibody titers were immunoglobulin M (IgM)/IgG 1:128/1:256. He had successful desensitization to anti-AB titer of <1:2 (IgM/IgG) with excellent outcome. Case 2: At the time of transplant, a patient had no anti-HLA-DSA. ABO titers were reduced to <1:8 (IgM/IgG) from baseline of IgM/IgG 1:128/1:1024 after desensitization. Posttransplant patient had severe acute graft dysfunction within 1 week, with rebound of anti-B titers to (IgM/IgG) 1:128/1:1024. Graft biopsy showed cortical necrosis resulting in graft loss. Case 3: His first ABO-compatible transplant was lost because of de novo anti-HLA-DSA, which developed within 1 week after transplant. The patient underwent the second ABO-i transplant. He also had anti-HLA-DSA against the second donor. Despite desensitization and anti-ABO titers coming down to <1:8, the patient developed severe acute graft dysfunction within 2 weeks, with rebound of anti-HLA-DSA antibody (titers increased >11000) resulting in graft loss. Conclusions: Careful evaluation of immunological barriers before ABO-i transplantation should be done, especially when both anti-HLA and ABO sensitization are present.