Immunological Barriers in ABO-Incompatible Kidney Transplantation: How to Overcome

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Abstract

Various desensitization strategies have been attempted to overcome immunologic barriers such as anti-human leukocyte antigen (HLA) donor-specific antibody (DSA) and ABO blood group incompatibility. However, there are still many problems to be resolved as the antibody that is responsible for post-transplant ABO-related acute ABMR must be an antibody that was newly synthesized after transplantation (de novo antibody, i.e., anti-ABO histo group antibody or HLA antibody), very high anti-ABO antibody producers are difficult to desensitize. Three index cases of ABO-incompatible kidney transplant their living-related donors. Each recipient was evaluated by complement dependent cytotoxicity (CDC) crossmatch, flow crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch Desensitaztion. The desensitization protocol for ABO incompatibile transplant at our centre includes infusion of 500 mg of Rituximab which is administered, 10 to 12 days prior to KT. 2 to 10 sessions of plasmapheresis depending on titer performed over 2 to 14 days before surgery until a recipient’s isoagglutinin titer decreased to a level below 1:8. Postoperative Plasmapheresis was performed only when the antiA,B isoagglutinin titer was above a level of 1:8 within first two weeks of transplant or patient has graft dysfunction with graft biopsy is suggestive of ABMR. All the ABO-i KT patients received induction therapy with either Basiliximab (an anti-CD25 monoclonal antibody) on the day of kidney transplant (KT). Plasmapheresis with IVIG infusions initiated from Day -10. During plasmapheresis, plasma is replaced with FFP and 5% Albumin. Immunosuppressants (Tacrolimus and MMF) were started 10 days prior to surgery. During the transplant surgery 500 mg of iv methylprednisolone is given. Titres of anti-A and/or Anti-B are monitored on daily basis with target levels being<1:8 by serial tube dilution method on the day of transplant. Induction with Basiliximab (on day 0 and 4) is given in most patients. In high-risk patients, rabbit ATG was given in a total dose of 3-4.5 mg/kg on Day 0 and then alternate days post-transplant

Case 1:In our center a patient had third time transplant, which underwent ABO incompatible transplant. At the time of transplant, donor specific antibodies were negative, ABO titers became <1:8 and patient have successful transplantation.

Case: 2 At the time of transplant, donor specific antibodies were negative, ABO titers became <1:8. Patient developed acute graft dysfunction within 1 week, patient's anti b titres had increased patient was started anti ABO antibodies desensitization. Patient graft biopsy shows cortical necrosis. in view of persistent hematuira & passing fleshy mass pu. Patient was planned for graft nephrectomy,

Case: 3 post-transplant ABO-related acute ABMR must be an antibody that was newly synthesized (de novo antibody, i.e., anti-ABO histo group antibody or HLA antibody), at the time of transplant, DSA was negative, ABO titers became <1:8. Patient developed acute graft dysfunction within 1-2 week; patient's HLA DSA antibody (MFI) titers had increased >1000 and graft loss.

We should carefully evaluate immunological barriers (anti-human leukocyte antigen (HLA) donor-specific antibody (DSA) and ABO blood group incompatibility) before ABOi transplantation specially when concomitant anti HLA sensitization is present.

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