O232: Enzymatic blood group conversion prevents complement activation in an ABO-incompatible model of human kidney transplantation

Abstract

Abstract Introduction Recently, enzymatic blood group conversion has been used to convert human kidneys from blood group A to universal blood group O using bacterial enzymes from Flavonifractor plautii. However, little is known about the functional consequences of antigen removal when a treated kidney is transplanted in an ABO-incompatible (ABOi) recipient. Here, we investigated classical complement activation during ABOi conditions in enzyme treated (ABOe) vs control human type A kidneys. Method Three biological pairs of type A human kidneys rejected for transplantation and offered for research were used in this study. One kidney per pair was treated with 1mg/L of FpGalNAc deacetylase and FpGalactosaminidase during 6hrs of hypothermic machine perfusion while the contralateral kidney was perfused without enzymes. Both kidneys were subsequently perfused for 4hrs in ABOi conditions using normothermic machine perfusion (10% AB serum; mouse anti-A IgM titre 1:128; type O red blood cells). Tissue-bound components of classical complement activation were assessed in pre- and post-perfusion biopsies. Results Following ABOi perfusion, control kidneys showed peritubular deposition of the classical complement component C1qA and further complement activation components C4d and C5b-9. The staining directly co-localised with regions of anti-A staining. In ABOe kidneys, no anti-A staining was observed, with no C1qA, C4d, or C5b-9 staining found in post-perfusion biopsies. Conclusions We have shown for the first time that ABOe kidneys do not activate the classical complement pathway in ABOi conditions. This work shows the potential of the enzymatic blood group conversion to evade hyperacute antibody-mediated rejection during renal transplantation.