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

Abstract

Background: The 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 presentation: A 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 immunoglobulins. 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.

Conclusion: Two 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.

Figure 1

Kidney transplant biopsy 12 weeks after ABO-incompatible kidney transplantation. A. Severe hemorrhage of the cortex and congestion of the glomeruli and tubulointerstitial compartment, with only minimal influx of inflammatory cells. There is a thrombus in the arteriole of the glomerulus. (H&E staining; original magnification 10×). B. Congestion of the glomerulus with fibrinoid necrosis of the arteriole. There is ischemia of the tubuli. An artery shows a transmural inflammation, of both mononuclear cells and neutrophiles. (Periodic acid-Schiff-Diastase stain; original magnification 20×) C. Positive staining of more than 50% of the peritubular capillaries and all the glomeruli. (Immunohistochemistry for C4d; original magnification 10×).

Figure 2

Course of anti-A antibody titers before and after ABO-incompatible kidney transplantation. The anti-A IgM (A) and IgG (B) titers were 64 and 32 respectively before pre-operative immunoadsorption (December 13th), decreased to 2/2 pre-operatively (December 20th) and were 1/<2 at discharge. During AMR they increased to >5000/512, decreasing to 256/32 one month later (logarithmic scale).