Late antibody-mediated rejection after ABO-incompatible kidney transplantation during Gram-negative sepsis

Abstract

BackgroundThe major challenge in ABO-incompatible transplantation is to minimize antibody-mediated rejection. Effective reduction of the anti-ABO blood group antibodies at the time of transplantation has made ABO-incompatible kidney transplantation a growing practice in our hospital and in centers worldwide. ABO antibodies result from contact with A- and B-like antigens in the intestines via nutrients and bacteria. We demonstrate a patient with fulminant antibody-mediated rejection late after ABO-incompatible kidney transplantation, whose anti-A antibody titers rose dramatically following Serratia marcescens sepsis.Case presentationA 58-year-old woman underwent an ABO-incompatible kidney transplantation for end-stage renal disease secondary to autosomal dominant polycystic kidney disease. It concerned a blood group A1 to O donation. Pre-desensitization titers were 64 for anti-blood group A IgM and 32 for anti-blood group A IgG titers. Desensitization treatment consisted of rituximab, tacrolimus, mycophenolate mofetil, corticosteroids, immunoadsorption and intravenous immunoglobulines. She was readmitted to our hospital 11 weeks after transplantation for S. marcescens urosepsis. Her anti-A IgM titer rose to >5000 and she developed a fulminant antibody-mediated rejection.We hypothesized that the (overwhelming) presence in the blood of S. marcescens stimulated anti-A antibody formation, as S. marcescens might share epitopes with blood group A antigen. Unfortunately we could not demonstrate interaction between blood group A and S. marcescens in incubation experiments.ConclusionTwo features of this post-transplant course are remarkably different from other reports of acute rejection in ABO-incompatible kidney transplantation: first, the late occurrence 12 weeks after kidney transplantation and second, the very high anti-A IgM titers (>5000), suggesting recent boosting of anti-A antibody formation by S. marcescens.

Post‐Transplantation Immunoadsorption Can Be Withheld in ABO‐Incompatible Kidney Transplant Recipients

“…One patient was also treated with r‐ATG because of insufficient renal function recovery. One patient with AMR Banff type 3 underwent transplantectomy .…”

“…Twelve month follow‐up was available for 26 patients in the postoperative IA group: two patients had died (suicide and abdominal sepsis) and two grafts failures occurred (month 3 ongoing rejection and month 4 intractable AMR during Gram‐negative sepsis ). 35 patients without postoperative IA had one‐year follow‐up.…”

Laboratory support of ABO antibody monitoring for ABO-incompatible solid organ transplantation

“…However, there was a case in which the ABO antibody titer increased rapidly due to sepsis, resulting in graft rejection several months after transplantation [ 24 ]. In this regard, it has been hypothesized that primary sensitization occurs due to ABO-associated antigens.…”

“…The British Society for Haematology guidelines also state that there is no issue with transfusion of blood components of the patient's blood type 4 weeks after transplant [23]. However, there was a case in which the ABO antibody titer increased rapidly due to sepsis, resulting in graft rejection several months after transplantation [24]. In this regard, it has been hypothesized that primary sensitization occurs due to ABO-associated antigens.…”

Galectin-4 Antimicrobial Activity Primarily Occurs Through its C-Terminal Domain

“…In contrast to red blood cell (RBC)-induced alloantibody formation ( 13 , 14 , 15 , 16 , 17 , 18 , 19 ), antibodies against ABO(H) antigens are naturally occurring and form within the first few months of life ( 20 ). While conflicting data exist regarding the development of naturally occurring anti-ABO(H) antibodies ( 21 , 22 , 23 , 24 , 25 ), several studies suggest that microbes that express ABO(H)-like antigens may stimulate anti-ABO(H) antibody formation relevant to transfusion and transplantation ( 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ). However, as tolerance mechanisms prevent the formation of anti-ABO(H) antibodies in ABO(H) blood group–positive individuals, how these individuals protect themselves against blood group–decorated microbes is incompletely understood.…”