The most important transplantation antigen system in solid organ transplantation is the ABO histo-blood group system. Crossing the ABO barrier in solid organ transplantation is usually not done except for emergency liver transplantations. Early experiences of crossing the ABO barrier in renal transplantation were very disappointing. In the 1970s, clinical trials were started transplanting kidneys of subgroup A2 into blood group O recipients. The tissues of the A2 subgroup expresses reduced amount of A antigens compared to subgroup A1 and the recipients had no special pretreatment and standard immunosuppression. A number of early graft losses were experienced but the trial also resulted in several long time surviving grafts. A few centres have adapted the concept of A2 to non A kidney transplantations with successful results, when the recipient anti-A titres are low or reduced prior to transplantation. In the early 1980s one group successfully transplanted A1 and B kidneys from living related donors across the ABO-barrier using an immunosuppressive protocol consisting of quadruple drugs and splenectomy and this protocol was adapted by a few other groups. In Japan, where cadaver donors are available in very limited number, the largest number of ABO-incompatible transplantations have been performed. Altogether more than 300 ABO-incompatible kidney transplantations have been performed in more than 40 centres since 1989. ABO-incompatible liver transplantations have been performed mainly in emergency cases and the results have generally been inferior to ABO-compatible grafts. In children below the age of three years, liver transplantations across the ABO-barrier have been quite successful especially with living related donors. Very few ABO-incompatible heart/heart-lung/lung-transplantations have been reported with a few successful cases, but the majority have been failures. Recently a series of ABO-incompatible heart transplants performed in small children have been reported with a high success rate.

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Key Points• A new histo-blood group system was discovered, based on the identification of Forssman glycolipid antigen on human red blood cells.• A newly described polymorphism in the GBGT1 gene activates the encoded enzyme to synthesize Forssman antigen. IntroductionCarbohydrate histo-blood group antigens, first recognized on red blood cells (RBCs) in 1900, 1 have been suggested to be part of our innate immune response. 2 Major carbohydrate histo-blood groups in man include the ABO, P1PK, H, Lewis, I, and GLOB systems in which glycoproteins and glycolipids carry immunodominant terminal sugars, 3 defining polymorphic antigens. Other mammals also express carbohydrate histo-blood groups, such as ABO, 4 fucoseless B antigen (Galili), 5 and Forssman (Fs) 6,7 but their expression on RBCs varies among species. Although the biologic function of polymorphic carbohydrates on RBCs is unresolved, these antigens can be used as receptors by pathogens [8][9][10][11] and their expression in tissues and bodily secretions are thus believed to reflect microbial selection. 8 In response to blood-group-mimicking glycans on bacterial surfaces, naturally occurring antibodies with the capacity to neutralize various microorganisms are formed. However, these antibodies also constitute substantial transfusion and transplantation barriers. 3,12 In 1987, 3 families with a supposed ABO subgroup named A pae were reported. 13 Although Helix pomatia lectin reacted strongly and polyclonal anti-A weakly with RBCs from some family members, monoclonal (MAb) anti-A reagents were later shown to be nonreactive, thus presenting an apparent paradox. The biochemical and genetic background of this enigmatic phenotype has remained unknown, as has its biologic consequences. We hypothesized that an explanation may be found by studying the glycolipids of this phenotype. 14 Here we report the identification of Fs glycolipids, normally found only on RBCs of selected nonprimate mammals, are strongly expressed on human A pae RBCs. In nonprimates, Fs antigen is synthesized by Fs synthase (globoside 3-␣-N-acetyl-D-galactosaminyltransferase, EC2.4.1.88), 7 an enzyme homologous to the ABO transferase. We also reveal a genetic polymorphism in the human Fs gene (GBGT1) that alters the enzymatically inactive human protein 15 Methods SamplesFive and 3 RBC units were collected from each of 2 unrelated A pae individuals (A pae #1 and A pae #2, respectively) from 2 of the originally reported families. 13 GlycolipidsGlycolipid preparation. Lysed blood units were thawed and total neutral glycolipids with Ͻ 20 sugar residues were isolated (see supplemental Methods, where control glycolipid preparations are also described; available on the Blood Web site; see the Supplemental Materials link at the top of the online article).Open-column chromatography. Total glycolipids (ϳ 110 mg) from each of A pae #1 and #2 were fractionated by silica chromatography column (5g silica/100 mg lipid; Silica 60, Merck) in a system of chloroform (C) methanol (M) solvent mixes (supplemental Metho...

XM-ONE is quick, easy to perform on whole blood samples and identifies patients at risk for rejection and reduced graft function not identified by conventional lymphocyte crossmatches.