Cascade Filtration for ABO Incompatible Transplant

Barrier of ABO

More than 30% of end-stage renal disease patients with an available living donor organ cannot be transplanted because of HLA or ABO incompatibility (ABOi). Such barriers can be overcome through paired exchange programs or desensitization strategies. Although paired exchange programs theoretically represent a solution, blood group type O recipients are disadvantaged because they can receive organs only by donors of their same blood group. For this reason, the general approach to overcome ABOi barrier is to use desensitization strategies.

ABO blood group antigens are expressed on the surface of red blood cells, lymphocytes, platelets, and endothelial and epithelial cells. These antigens are polysaccharides added on the core of O blood type group, by a specific glycosyltransferase. Antibodies versus blood groups can be either IgM or IgG. However, in the contest of transplantation, IgG are functionally significant. They are produced against those antigens not native to the host so that blood type O has antibodies against A and B, blood type A and B have antibodies against B and A antigens respectively, whereas blood type AB had no antibodies. They usually are referred to as natural antibody, because they are produced during the development of immune system against cross-reactive epitopes on the cell wall of gut bacteria, in a T cell–independent way. Extrafollicular B1 cells are mainly responsible for ABO antibody production.

First attempts to perform ABOi renal transplantation were made in the 1960s and 1970s with very poor outcomes. ABOi was considered an insurmountable barrier until Alexandre reported his pioneer experience in the end of the 1980s. He obtained encouraging results using plasma exchange (PE) and platelet transfusions plus splenectomy at the time of renal transplantation. This was the standard protocol for 20 years. It was only the beginning of the history, and from that point, preconditioning measurement before ABOi transplantation was employed.

Now it is clear that a desensitization program has to reduce antibodies by removing circulating immunoglobulins and reducing their production through elimination of antibody-producing cells. Before the introduction of the monoclonal antibody anti-CD20, rituximab, splenectomy was the standard to reduce synthesis of anti–blood type antibodies. The spleen is the main site of natural antibodies production, and splenectomy was associated favorably with outcomes. However, it increases surgical and infective risks, especially in the setting of chronic immunosuppressive therapy. Rituximab is directed against CD20 ⁺ B cells, which realizes a pharmacologic splenectomy, and after its administration, no more splenic B cells are detectable. However, plasma cells lack CD20, and they continue to produce anti–blood type antibodies, which must be removed before ABOi transplantation. Recently, a protocol without the use of rituximab was suggested in low-risk patients. Regardless of strategy used to reduce antibody synthesis, temporary removal of antibodies from the recipient's serum is mandatory.