NIV Congres

Introduction The major challenge in blood group ABO-incompatible (ABOi) transplantation is to minimize antibody-mediated rejection (AMR). Recently developed protocols aim for effective reduction of the ABO antibodies at the time of transplantation and allow for accommodation of the immune response afterwards. ABOi-related AMR occurs almost exclusively in the first weeks after transplantation. ABO antibodies result from contact with A- and B-like antigens in the intestines via nutrients and gut-associated bacteria. Theoretically, boosting of the anti-ABO immune response by any of these bacteria is potentially harmful as it may trigger AMR of ABOi kidney grafts. We demonstrate a patient with fulminant antibody-mediated rejection after ABOi kidney transplantation, whose anti-A IgM titers rose dramatically following Serratia marcescens (S. marcescens) sepsis.

Case report A 58-year-old woman underwent an ABOi kidney transplantation (A to O donation) for end-stage renal disease secondary to autosomal dominant polycystic kidney disease. Pre-desensitization titers of anti-A were 64 for IgM and 32 for IgG. These were successfully reduced to <1:8 after immunoadsorption. Immune suppressive treatment consisted of rituximab, tacrolimus, mycophenolate mofetil, prednisone and immunoglobulines. She was discharged with a serum creatinine of 113 umol/L. She was readmitted to our hospital 12 weeks after transplantation for S. marcescens urosepsis. Her anti-A IgM titer rose to >5000 and a fulminant biopsy proven AMR followed, necessitating transplantectomy.

We hypothesized that the S. marcescens sepsis had stimulated anti-A antibody formation. Bacteria known to have cross reactivity with ABO antigens, can decrease erythrocyte agglutination by absorption of anti-ABO immunoglobulins. Therefore, we conducted a number of experiments to show that pre-incubation of anti-A sera with S. marcescens bacteria was able to block haemagglutination of blood group A erythrocytes. However, none of these experiments indicated the ability of S. marcescens to bind anti-A antibodies.

Conclusion This case illustrates that antibody mediated rejection may occur exceptionally late after kidney transplantation. The very high anti-A titers (IgM >5000) suggest a recent challenge of the immune system with blood group A antigen. The concurrent urosepsis with S. marcescens is highly suggestive for a pathological role of this microorganism but we were unable to verify this with in vitro experimental evidence.